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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
        <publisher-loc>S&#227;o Paulo, SP, Brazil</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">xWxKN3rTgRcb7QKLBxJJ59f</article-id>
      <article-id pub-id-type="other">00008</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2009000600008</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(09)09200608</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2009000600008</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Efeito da respira&#231;&#227;o diafragm&#225;tica sobre a variabilidade da frequ&#234;ncia card&#237;aca na doen&#231;a card&#237;aca isqu&#234;mica com diabete</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Kulur</surname>
            <given-names>Anupama Bangra</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Haleagrahara</surname>
            <given-names>Nagaraja</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Adhikary</surname>
            <given-names>Prabha</given-names>
          </name>
          <xref ref-type="aff" rid="aff03"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Jeganathan</surname>
            <given-names>P. S.</given-names>
          </name>
          <xref ref-type="aff" rid="aff03"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">Kuala Lumpur</named-content>
        </addr-line>
        <institution content-type="orgname">University College of Sedaya International</institution>
        <institution content-type="orgdiv1">Faculty of Medicine </institution>
        <country country="MY">Malaysia</country>
      </aff>
      <aff id="aff03">
        <addr-line>
          <named-content content-type="city">Mangalore</named-content>
          <named-content content-type="state"/>
        </addr-line>
        <institution content-type="orgname">Manipal University</institution>
        <institution content-type="orgdiv1">Faculty of Medicine </institution>
        <country country="IN">India</country>
      </aff>
      <aff id="aff02">
        <addr-line>
          <named-content content-type="city">Kuala Lumpur</named-content>
        </addr-line>
        <institution content-type="orgname">International Medical University</institution>
        <institution content-type="orgdiv1">School of Medicine </institution>
        <country country="MY">Malaysia</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>06</month>
        <year>2009</year>
      </pub-date>
      <volume>92</volume>
      <issue>6</issue>
      <fpage>457</fpage>
      <lpage>463</lpage>
      <history>
        <date date-type="rev-recd">
          <day>26</day>
          <month>04</month>
          <year>2008</year>
        </date>
        <date date-type="received">
          <day>13</day>
          <month>01</month>
          <year>2008</year>
        </date>
        <date date-type="accepted">
          <day>08</day>
          <month>05</month>
          <year>2008</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" xml:lang="en">
          <license-p>This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>FUNDAMENTO: A diminui&#231;&#227;o da variabilidade da frequ&#234;ncia card&#237;aca (VFC) est&#225; associada com um progn&#243;stico desfavor&#225;vel em pacientes com doen&#231;a card&#237;aca isqu&#234;mica (DCI) e diabete. Ainda n&#227;o foi provado em definitivo se a mudan&#231;a no padr&#227;o respirat&#243;rio pode modificar o fator de risco nesses pacientes. OBJETIVO: Avaliar o efeito da respira&#231;&#227;o diafragm&#225;tica sobre a VFC em pacientes diab&#233;ticos com DCI. M&#201;TODOS: A popula&#231;&#227;o do estudo consistiu em 145 pacientes do sexo masculino selecionados ao acaso, dos quais 45 apresentavam DCI, 52 apresentavam DCI e diabete (DCI-DM) e 48 apresentavam DCI e neuropatia diab&#233;tica (DCI-ND). A VFC foi avaliada atrav&#233;s de ECG de 5 minutos usando o m&#233;todo de dom&#237;nio de tempo. O grupo de interven&#231;&#227;o foi dividido em grupo aderente e n&#227;o-aderente e o seguimento foi registrado ap&#243;s tr&#234;s meses e um ano. RESULTADOS:A avalia&#231;&#227;o basal mostrou uma diminui&#231;&#227;o significante em VFC nos pacientes com doen&#231;a card&#237;aca isqu&#234;mica com ou sem diabete (p&lt;0,01). Os pacientes com DCI apresentavam VFC mais alta do que os pacientes com DCI-DM (p&lt;0,01) e DCI-ND (p&lt;0,01). Um aumento na VFC foi observado em pacientes que praticaram respira&#231;&#227;o diafragm&#225;tica por tr&#234;s meses (DCI-DM: p&lt;0,01; DCI-ND: p&lt;0,05) e por um ano (DCI-DM: p&lt;0,01; DCI-ND: p&lt;0,01). A VFC diminuiu significantemente ap&#243;s um ano em pacientes n&#227;o-aderentes. A pr&#225;tica regular de respira&#231;&#227;o diafragm&#225;tica tamb&#233;m melhorou o &#237;ndice glic&#234;mico nesses pacientes. CONCLUS&#195;O: A pr&#225;tica regular de respira&#231;&#227;o diafragm&#225;tica melhora de forma significante a VFC em uma dire&#231;&#227;o prognosticamente favor&#225;vel em pacientes com DCI e diabete. Esses efeitos parecem ser potencialmente ben&#233;ficos no manejo desses pacientes.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Respira&#231;&#227;o</kwd>
        <kwd>frequ&#234;ncia card&#237;aca</kwd>
        <kwd>insufici&#234;ncia card&#237;aca</kwd>
        <kwd>diabetes mellitus</kwd>
        <kwd>isquemia mioc&#225;rdica</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>17</day>
        <month>07</month>
        <year>2009</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>ARTIGO ORIGINAL </p>
    <p> ELETROCARDIOGRAFIA</p>
    <p>Efeito da respira&#231;&#227;o diafragm&#225;tica sobre a variabilidade da frequ&#234;ncia card&#237;aca na doen&#231;a card&#237;aca isqu&#234;mica com diabete</p>
    <p>
      <bold>Anupama Bangra Kulur<sup>I</sup>; Nagaraja Haleagrahara<sup>II</sup>; Prabha Adhikary<sup>III</sup>; Jeganathan P. S.<sup>III</sup></bold>
    </p>
    <p><sup>I</sup>Faculty of Medicine, University College of Sedaya International, Kuala Lumpur, Malaysia </p>
    <p><sup>II</sup>School of Medicine, International Medical University, Kuala Lumpur, Malaysia </p>
    <p><sup>III</sup>Faculty of Medicine, Kasturba Medical College, Mangalore - &#205;ndia</p>
    <p>
      <xref ref-type="corresp" rid="end">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO:</bold> A diminui&#231;&#227;o da variabilidade da frequ&#234;ncia card&#237;aca (VFC) est&#225; associada com um progn&#243;stico desfavor&#225;vel em pacientes com doen&#231;a card&#237;aca isqu&#234;mica (DCI) e diabete. Ainda n&#227;o foi provado em definitivo se a mudan&#231;a no padr&#227;o respirat&#243;rio pode modificar o fator de risco nesses pacientes. </p>
    <p><bold>OBJETIVO: </bold>Avaliar o efeito da respira&#231;&#227;o diafragm&#225;tica sobre a VFC em pacientes diab&#233;ticos com DCI. </p>
    <p><bold>M&#201;TODOS: </bold>A popula&#231;&#227;o do estudo consistiu em 145 pacientes do sexo masculino selecionados ao acaso, dos quais 45 apresentavam DCI, 52 apresentavam DCI e diabete (DCI-DM) e 48 apresentavam DCI e neuropatia diab&#233;tica (DCI-ND). A VFC foi avaliada atrav&#233;s de ECG de 5 minutos usando o m&#233;todo de dom&#237;nio de tempo. O grupo de interven&#231;&#227;o foi dividido em grupo aderente e n&#227;o-aderente e o seguimento foi registrado ap&#243;s tr&#234;s meses e um ano. </p>
    <p><bold>RESULTADOS:</bold>A avalia&#231;&#227;o basal mostrou uma diminui&#231;&#227;o significante em VFC nos pacientes com doen&#231;a card&#237;aca isqu&#234;mica com ou sem diabete (p&lt;0,01). Os pacientes com DCI apresentavam VFC mais alta do que os pacientes com DCI-DM (p&lt;0,01) e DCI-ND (p&lt;0,01). Um aumento na VFC foi observado em pacientes que praticaram respira&#231;&#227;o diafragm&#225;tica por tr&#234;s meses (DCI-DM: p&lt;0,01; DCI-ND: p&lt;0,05) e por um ano (DCI-DM: p&lt;0,01; DCI-ND: p&lt;0,01). A VFC diminuiu significantemente ap&#243;s um ano em pacientes n&#227;o-aderentes. A pr&#225;tica regular de respira&#231;&#227;o diafragm&#225;tica tamb&#233;m melhorou o &#237;ndice glic&#234;mico nesses pacientes. </p>
    <p><bold>CONCLUS&#195;O: </bold>A pr&#225;tica regular de respira&#231;&#227;o diafragm&#225;tica melhora de forma significante a VFC em uma dire&#231;&#227;o prognosticamente favor&#225;vel em pacientes com DCI e diabete. Esses efeitos parecem ser potencialmente ben&#233;ficos no manejo desses pacientes.</p>
    <p><bold>Palavras-chave: </bold>Respira&#231;&#227;o, frequ&#234;ncia card&#237;aca, insufici&#234;ncia card&#237;aca, <italic>diabetes mellitus</italic>, isquemia mioc&#225;rdica.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>A variabilidade da frequ&#234;ncia card&#237;aca (VFC) &#233; a natural eleva&#231;&#227;o e diminui&#231;&#227;o da frequ&#234;ncia card&#237;aca em resposta &#224; respira&#231;&#227;o, press&#227;o arterial, horm&#244;nios e emo&#231;&#245;es<sup>1</sup>. Ela &#233; vista como sendo refletiva e preditiva da sa&#250;de e da doen&#231;a psicol&#243;gica em geral. AVFC representa uma dos marcadores mais promissores da atividade auton&#244;mica<sup>2</sup>. Uma VFC deficiente tem sido observada em muitos quadros cl&#237;nicos, incluindo a neuropatia auton&#244;mica, transplante card&#237;aco, insufici&#234;ncia card&#237;aca congestiva, infarto do mioc&#225;rdio e outras doen&#231;as card&#237;acas e n&#227;o-card&#237;acas<sup>3</sup>. V&#225;rios estudos t&#234;m demonstrado redu&#231;&#227;o na VFC em pacientes com doen&#231;a card&#237;aca isqu&#234;mica (DCI)<sup>4,5</sup>. O mecanismo da redu&#231;&#227;o da VFC na doen&#231;a card&#237;aca isqu&#234;mica n&#227;o &#233; conhecido<sup>5,6</sup>. Isquemia cr&#244;nica ou intermitente pode ter um papel importante, j&#225; que foi demonstrado que epis&#243;dios isqu&#234;micos est&#227;o associados com t&#244;nus vagal reduzido de forma aguda<sup>7</sup>. </p>
    <p>A neuropatia auton&#244;mica diab&#233;tica afeta aproximadamente 40% de todos os pacientes diab&#233;ticos e em sua forma grave, oferece um progn&#243;stico ruim<sup>8</sup>. Como a VFC reflete o grau de controle auton&#244;mico do cora&#231;&#227;o, ela &#233; amplamente utilizada para o diagn&#243;stico das disfun&#231;&#245;es auton&#244;micas em doen&#231;as n&#227;o-card&#237;acas, considerando-se que, se tal disfun&#231;&#227;o card&#237;aca for identificada, &#233; um sinal de uma neuropatia auton&#244;mica mais generalizada, afetando todos os &#243;rg&#227;os<sup>9</sup>. Tem sido observado que a neuropatia auton&#244;mica diab&#233;tica cardiovascular est&#225; associada com a perda da variabilidade da frequ&#234;ncia card&#237;aca. Na neuropatia associada com <italic>diabetes mellitus</italic>, caracterizada pela altera&#231;&#227;o das pequenas fibras nervosas, uma redu&#231;&#227;o nos par&#226;metros do dom&#237;nio de tempo da VFC parece n&#227;o apenas ter um valor progn&#243;stico negativo, mas tamb&#233;m preceder a express&#227;o cl&#237;nica da neuropatia auton&#244;mica<sup>10,11</sup>.</p>
    <p>Devido ao fato de a diminui&#231;&#227;o da VFC estar associada com um resultado adverso, os pesquisadores conclu&#237;ram que o aumento na VFC aumentaria tamb&#233;m as taxas de sobreviv&#234;ncia. </p>
    <p>Muitas das interven&#231;&#245;es associadas com a diminui&#231;&#227;o da mortalidade, como pr&#225;tica de exerc&#237;cios, abandono do h&#225;bito de fumar, terapia medicamentosa, tamb&#233;m est&#227;o associadas com o aumento da VFC<sup>10-12</sup>. Sabe-se que a atividade respirat&#243;ria influencia a frequ&#234;ncia card&#237;aca atrav&#233;s de mecanismos fisiol&#243;gicos e anat&#244;micos<sup>13</sup>. </p>
    <p>O refreamento respirat&#243;rio atrav&#233;s da t&#233;cnica de respira&#231;&#227;o lenta &#233; uma terapia adjunta &#250;til para o controle cardiorrespirat&#243;rio<sup>14</sup>. De acordo com Chacko e cols.<sup>15</sup> a respira&#231;&#227;o lenta a 6 ciclos por minuto aumenta a sensibilidade barorreflexa em indiv&#237;duos normais e em pacientes com insufici&#234;ncia card&#237;aca<sup>15</sup>. Sabe-se que a respira&#231;&#227;o abdominal lenta diminui a atividade do sistema nervoso simp&#225;tico<sup>16</sup> e tem sido demonstrado que a respira&#231;&#227;o abdominal reduz a recorr&#234;ncia de eventos coronarianos em indiv&#237;duos que j&#225; sofreram um infarto. Sabe-se que esse tipo de respira&#231;&#227;o reduz a tens&#227;o no m&#250;sculo respirat&#243;rio, reduz a sintomatologia funcional e reduz a ansiedade e promove sensa&#231;&#227;o de relaxamento<sup>17</sup>. Evid&#234;ncias recentes sugerem que a respira&#231;&#227;o lenta diminui a press&#227;o arterial em pacientes com hipertens&#227;o leve e moderada e em pacientes com hipertens&#227;o resistente, sem mudan&#231;as na medica&#231;&#227;o<sup>18</sup>. </p>
    <p>H&#225; poucos estudos sobre o efeito das manobras de respira&#231;&#227;o diafragm&#225;tica sobre a VFC em pacientes com <italic>diabetes mellitus</italic>. Assim, o presente estudo foi realizado com o principal objetivo de determinar a VFC em pacientes com DCI e diabete, com ou sem neuropatia auton&#244;mica. Nossa hip&#243;tese de estudo foi que a pr&#225;tica regular de respira&#231;&#227;o diafragm&#225;tica melhora a VFC em pacientes com DCI e diabete. </p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>O grupo de estudo consistiu em 145 indiv&#237;duos do sexo masculino, selecionados ao acaso, no Kasturba Medical College Hospital, da Universidade Manipal, &#205;ndia, cuja idade variava de 40 -70 anos. O grupo de pacientes tinha 45 pacientes com DCI sem diabete, 52 pacientes com DCI e <italic>diabetes mellitus</italic> tipo 2 e 48 pacientes remanescentes com DCI e neuropatia auton&#244;mica diab&#233;tica. Ap&#243;s os crit&#233;rios de inclus&#227;o e exclus&#227;o terem sido aplicados, os pacientes foram entrevistados e submetidos a exame f&#237;sico geral. Os dados dos indiv&#237;duos sobre o perfil cl&#237;nico, tratamento farmacol&#243;gico e perfil epidemiol&#243;gico foram coletados. Altura, peso, raz&#227;o cintura-quadril, press&#227;o arterial, frequ&#234;ncia card&#237;aca e frequ&#234;ncia respirat&#243;ria foram obtidos e um exame sist&#234;mico completo foi realizado. Um eletrocardiograma (ECG) de 12 deriva&#231;&#245;es foi realizado e os achados foram registrados. Glicemia de jejum foi medida na amostra de sangue atrav&#233;s do m&#233;todo de glicose desidrogenase. A hemoglobina glicada (HbA<sub>1C</sub>) foi medida pelo m&#233;todo imunoturbidim&#233;trico. </p>
    <p>Pacientes diagnosticados com angina, infarto do mioc&#225;rdio ou infarto do mioc&#225;rdio com insufici&#234;ncia card&#237;aca e diabete foram inclu&#237;dos no grupo de estudo. Os crit&#233;rios de exclus&#227;o foram os seguintes: pacientes com doen&#231;a card&#237;aca valvular, doen&#231;a pulmonar obstrutiva, asma, cardiomiopatias, fibrila&#231;&#227;o atrial e bloqueio de ramo. O diagn&#243;stico da DCI foi documentado por evid&#234;ncia de ECG de infarto do mioc&#225;rdio pr&#233;vio, evid&#234;ncia de ECG de depress&#227;o do segmento ST, dor tor&#225;cica no teste de esfor&#231;o nos &#250;ltimos seis meses, angiografia coron&#225;ria mostrando &gt; 60% de estenose em uma art&#233;ria coron&#225;ria principal. Pacientes com <italic>diabetes mellitus</italic> (DM) foram classificados como tendo diabete com base no hist&#243;rico, independente da dura&#231;&#227;o da doen&#231;a ou necessidade de uso de agentes anti-diab&#233;ticos. A DM foi definida como glicemia de jejum <underline>&gt;</underline> 7,0 mmol/l. A neuropatia diab&#233;tica foi estabelecida quando dois ou mais testes reflexos cardiovasculares padr&#227;o da fun&#231;&#227;o auton&#244;mica foram anormais<sup>19,20</sup>. Os testes de fun&#231;&#227;o auton&#244;mica inclu&#237;am </p>
    <p>I) medida batimento-a-batimento da varia&#231;&#227;o da frequ&#234;ncia card&#237;aca durante ventila&#231;&#227;o medida, </p>
    <p>II) resposta postural da frequ&#234;ncia card&#237;aca (raz&#227;o 30:15),</p>
    <p>III) varia&#231;&#227;o da frequ&#234;ncia card&#237;aca durante uma manobra de Valsalva padronizada e </p>
    <p>IV) resposta hemodin&#226;mica &#224; postura ereta. Sessenta indiv&#237;duos saud&#225;veis pareados para idade foram usados como grupo controle. Eles n&#227;o apresentavam sintomas de nenhuma doen&#231;a, n&#227;o utilizavam medicamentos e apresentaram resultados normais ao eletrocardiograma de repouso. </p>
    <p>Os grupos de estudo eram bem balanceados em rela&#231;&#227;o aos dados demogr&#225;ficos e tratamento farmacol&#243;gico. Todos os indiv&#237;duos foram instru&#237;dos sobre o protocolo e deram seu consentimento livre e informado para participar do estudo. O estudo foi aprovado pelo Comit&#234; Institucional de &#201;tica e o mesmo est&#225; de acordo com os princ&#237;pios postulados na Declara&#231;&#227;o de Helsinki de 1983. </p>
    <p>
      <bold>An&#225;lise da variabilidade da frequ&#234;ncia card&#237;aca (VFC)</bold>
    </p>
    <p>O teste de frequ&#234;ncia card&#237;aca durante respira&#231;&#227;o profunda<sup>21-23</sup> foi conduzido com o indiv&#237;duo em posi&#231;&#227;o supina durante o registro eletrocardiogr&#225;fico padr&#227;o. Os indiv&#237;duos foram ensinados a respirar a uma taxa de 6 ciclos respirat&#243;rios por minuto; 5s para cada inala&#231;&#227;o e 5s para cada exala&#231;&#227;o. O ECG foi registrado de forma cont&#237;nua a 25 mm/segundo por 5 minutos enquanto os pacientes respiravam de acordo com as instru&#231;&#245;es recebidas. As altera&#231;&#245;es batimento-a-batimento na frequ&#234;ncia card&#237;aca foram avaliadas pelo m&#233;todo de dom&#237;nio de tempo. O intervalo R-R foi mensurado em cada ciclo respirat&#243;rio e um intervalo R-R m&#233;dio foi considerado para a mensura&#231;&#227;o da VFC. A variabilidade da frequ&#234;ncia card&#237;aca foi calculada como a diferen&#231;a entre os intervalos R-R mais curto e mais longo. O teste de frequ&#234;ncia card&#237;aca durante respira&#231;&#227;o profunda foi escolhido como um teste curto &#224; beira do leito, baseado na experi&#234;ncia alcan&#231;ada no teste de controle nervoso auton&#244;mico do cora&#231;&#227;o em pacientes com DM. O resultado do teste foi pr&#233;-especificado como normal se houvesse diferen&#231;a de 10 batimentos ou mais por minuto entre a frequ&#234;ncia mais lenta e a mais r&#225;pida.</p>
    <p>
      <bold>Respira&#231;&#227;o diafragm&#225;tica</bold>
    </p>
    <p>A respira&#231;&#227;o diafragm&#225;tica (respira&#231;&#227;o abdominal) foi ensinada aos pacientes e controles por um fisioterapeuta do hospital. Foi pedido aos indiv&#237;duos que realizassem a respira&#231;&#227;o diafragm&#225;tica na posi&#231;&#227;o supina. Foi pedido aos indiv&#237;duos que inalassem lenta e profundamente atrav&#233;s do nariz at&#233; o fundo dos pulm&#245;es, isto &#233;, enviando o ar t&#227;o profundamente para baixo nos pulm&#245;es quanto poss&#237;vel. O t&#243;rax move-se levemente enquanto o abd&#244;men se expande. O diafragma move-se para baixo. Ap&#243;s uma respira&#231;&#227;o profunda, era pedido ao paciente que segurasse a respira&#231;&#227;o por um momento e ent&#227;o exalasse lentamente atrav&#233;s de expira&#231;&#227;o controlada. </p>
    <p>O grupo de interven&#231;&#227;o de exerc&#237;cio respirat&#243;rio foi dividido prospectivamente entre aqueles que estavam dispostos a fazer os exerc&#237;cios regularmente (grupo aderente: 80 pacientes e 32 controles) e aqueles que n&#227;o estavam dispostos (grupo n&#227;o-aderente: 65 pacientes e 28 controles). Os pacientes e controles no grupo aderente foram encorajados a executar o exerc&#237;cio respirat&#243;rio diafragm&#225;tico completo 10 vezes de cada vez na posi&#231;&#227;o supina com intervalos de 30 s a 1 minuto de descanso e ent&#227;o, come&#231;ar de novo. Eles foram aconselhados a praticar a respira&#231;&#227;o diafragm&#225;tica por 10-15 minutos, duas vezes ao dia (de manh&#227; e &#224; noite), durante um ano e ent&#227;o voltar para observa&#231;&#227;o. Os pacientes e os controles foram acompanhados ambulatorialmente por um per&#237;odo de 12 meses, com visitas a intervalos de 30 dias. Durante a visita, o fisioterapeuta entrevistava os indiv&#237;duos e registrava os detalhes do regime de exerc&#237;cios respirat&#243;rios. Eles foram regularmente motivados a continuar com os exerc&#237;cios respirat&#243;rios. Os indiv&#237;duos foram orientados no hospital por um m&#233;dico sobre o manejo da doen&#231;a isqu&#234;mica card&#237;aca e DM tipo 2 e o papel dos exerc&#237;cios respirat&#243;rios no manejo das doen&#231;as. Cada indiv&#237;duo recebeu um caderno com instru&#231;&#245;es e benef&#237;cios dos exerc&#237;cios respirat&#243;rios e ilustra&#231;&#245;es da respira&#231;&#227;o abdominal. Os indiv&#237;duos foram orientados a tomar notas sobre o tratamento medicamentoso, dieta e outras atividades f&#237;sicas durante o per&#237;odo do estudo. Durante os 12 meses de seguimento, todos os indiv&#237;duos inclu&#237;dos no estudo foram supervisionados de perto por um m&#233;dico e um fisioterapeuta. Os resultados de ambos os grupos aderente e n&#227;o-aderente foram gravados para o registro do seguimento. Durante o per&#237;odo de seguimento de 3 e 12 meses, a VFC, glicemia de jejum, peso corporal e n&#237;veis de hemoglobina glicada foram registrados. As atividades f&#237;sicas dos indiv&#237;duos, peso corporal, terapia medicamentosa, dietas etc., foram verificadas e quaisquer problemas encontrados durante os exerc&#237;cios respirat&#243;rios foram discutidos. </p>
    <p>Todos os resultados foram expressos como m&#233;dia &#177; erro padr&#227;o da m&#233;dia ou n&#250;meros e porcentagens. O pacote estat&#237;stico para ci&#234;ncias sociais SPSS vers&#227;o 11 foi utilizado para todas as an&#225;lises estat&#237;sticas. O teste U de Mann-Whitney foi usado para comparar v&#225;rios par&#226;metros entre diferentes grupos. O Teste de Postos com Sinais (<italic>Wilcoxon Signed Rank Test</italic>) foi utilizado para comparar os resultados entre registros basais e de seguimento. Para avaliar se a respira&#231;&#227;o diafragm&#225;tica isolada influenciou a VFC, um teste de regress&#227;o m&#250;ltipla <italic>stepwise</italic> foi utilizado. Valores de p &lt; 0,05 foram considerados significantes em todas as an&#225;lises estat&#237;sticas. </p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>As caracter&#237;sticas cl&#237;nicas dos pacientes s&#227;o apresentadas na <xref ref-type="table" rid="tab01">Tabela 1</xref>. Os tr&#234;s grupos de estudo e o grupo controle eram bem equilibrados em rela&#231;&#227;o aos dados demogr&#225;ficos. Os grupos de estudo n&#227;o diferiam significativamente em rela&#231;&#227;o &#224; idade, dura&#231;&#227;o da diabete e medica&#231;&#227;o. Houve uma diminui&#231;&#227;o significativa na VFC nos pacientes com DCI sem diabete (p&lt;0,01) quando comparados com os controles saud&#225;veis. O grupo com DCI e <italic>diabetes mellitus</italic> (p&lt;0,01) e o grupo com neuropatia tamb&#233;m tinham VFC significantemente reduzida (p&lt;0,01) quando comparados aos controles. Os pacientes com DCI sem diabete apresentavam VFC significantemente mais alta (p&lt;0,05) do que aqueles com DCI sem DM e com neuropatia diab&#233;tica (ND). N&#227;o houve diferen&#231;a significante em rela&#231;&#227;o &#224; VFC entre o grupo com DCI e DM e o grupo com DCI e ND. A HbA<sub>1C</sub> e a glicemia de jejum eram significantemente mais altas no grupo com DCI e DM (p&lt;0,01) e no grupo com DCI e ND (p&lt;0,01), quando comparados com os grupos controle e DCI (<xref ref-type="table" rid="tab02">Tabela 2</xref>).</p>
    <table-wrap id="tab01">
      <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt01.jpg"/></table-wrap>
    <table-wrap id="tab02">
      <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt02.jpg"/></table-wrap>
    <p>Como visto na <xref ref-type="table" rid="tab03">Tabela 3</xref>, os pacientes com DCI sem DM e aqueles com DM com ou sem neuropatia mostraram um aumento significante na VFC (p&lt;0,01) ap&#243;s tr&#234;s meses e um ano de seguimento da respira&#231;&#227;o diafragm&#225;tica. Um aumento mais estatisticamente significante na VFC foi registrado (p&lt;0,01- para todos os grupos) ap&#243;s um ano de seguimento, em compara&#231;&#227;o com os registros basais em todos os grupos do estudo. Um aumento na VFC ap&#243;s o seguimento foi significantemente maior (p&lt;0.01) no grupo com DCI e DM do que no grupo DCI com ND.</p>
    <table-wrap id="tab03">
      <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt03.jpg"/></table-wrap>
    <p>A pr&#225;tica regular da respira&#231;&#227;o diafragm&#225;tica aumentou a VFC nos indiv&#237;duos controle tamb&#233;m ap&#243;s um ano (p&lt;0,01) (<xref ref-type="table" rid="tab03">Tabela 3</xref>). Uma diminui&#231;&#227;o significante nos n&#237;veis de HbA<sub>1C</sub> (p&lt;0,01) e glicose (p&lt;0,01) foi observada ap&#243;s 3 e 12 meses de seguimento no grupo aderente. Muito embora os n&#237;veis de HbA<sub>1C</sub> e glicose fossem significantemente mais altos (p&lt;0,01) do que nos controles e no grupo com DCI, a pr&#225;tica regular de respira&#231;&#227;o diafragm&#225;tica significantemente diminuiu esses par&#226;metros metab&#243;licos ap&#243;s 12 meses de seguimento, quando comparados com os n&#237;veis basais (<xref ref-type="table" rid="tab04">Tabela 4</xref>). A <xref ref-type="table" rid="tab05">Tabela 5</xref> mostra a VFC registrada nos controles n&#227;o-aderentes e nos pacientes com DCI ap&#243;s 3 meses e 12 meses. N&#227;o houve diferen&#231;a significante na VFC ap&#243;s 3 meses de seguimento em todos os grupos n&#227;o-aderentes. Houve uma diferen&#231;a significante na VFC nos pacientes com DCI sem DM (p&lt;0,01), DCI com DM (p&lt;0,01) e DCI com ND (p&lt;0,01) ap&#243;s um ano de seguimento do estudo (<xref ref-type="table" rid="tab05">Tabela 5</xref>). Nenhuma diferen&#231;a significante nos par&#226;metros metab&#243;licos (HbA<sub>1C</sub> e glicemia) foi registrada ap&#243;s o primeiro per&#237;odo de seguimento, mas a HbA<sub>1C</sub> aumentou significantemente ap&#243;s um ano de seguimento em pacientes com DCI e ND (p&lt;0,01). Os n&#237;veis de glicemia aumentaram significantemente em pacientes com DCI n&#227;o-aderentes sem DM (p&lt;0,05), DCI com DM (p&lt;0,01) e DCI com ND (p&lt;0,01) indicando que a condi&#231;&#227;o da doen&#231;a piorou na aus&#234;ncia da respira&#231;&#227;o diafragm&#225;tica (<xref ref-type="table" rid="tab06">Tabela 6</xref>).</p>
    <table-wrap id="tab04">
      <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt04.jpg"/></table-wrap>
    <table-wrap id="tab05">
      <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt05.jpg"/></table-wrap>
    <table-wrap id="tab06">
      <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt06.jpg"/></table-wrap>
    <p>Quando a VFC foi comparada entre os grupos aderente e n&#227;o-aderente ap&#243;s um ano de seguimento, um aumento mais significante foi registrado em todos os grupos, incluindo os controles (p&lt;0,01) (<xref ref-type="table" rid="tab07">Tabela 7</xref>). Nos grupos n&#227;o-aderentes, houve uma diminui&#231;&#227;o significante na VFC entre os pacientes com DCI e DM e pacientes com DCI e ND (p&lt;0.01) quando comparados com os pacientes aderentes.</p>
    <table-wrap id="tab07">
      <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt07.jpg"/></table-wrap>
    <p>A an&#225;lise de regress&#227;o m&#250;ltipla indicou que a respira&#231;&#227;o, isoladamente, foi respons&#225;vel por 58,8% (R=0,588) da varia&#231;&#227;o na VFC ap&#243;s um ano de seguimento. Quando outras vari&#225;veis preditivas foram inclu&#237;das, a contribui&#231;&#227;o da respira&#231;&#227;o aumentou para 72% (R=0,725). A respira&#231;&#227;o diafragm&#225;tica, isoladamente, mostrou uma maior contribui&#231;&#227;o para as mudan&#231;as observadas na VFC. O coeficiente da respira&#231;&#227;o diafragm&#225;tica foi o maior, mostrando o m&#225;ximo de contribui&#231;&#227;o em compara&#231;&#227;o a outros preditores, tais como medica&#231;&#227;o, dura&#231;&#227;o da diabete, idade, etc. </p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>O presente estudo mostrou que houve uma diminui&#231;&#227;o significante na VFC em pacientes com doen&#231;a card&#237;aca isqu&#234;mica e pacientes com doen&#231;a card&#237;aca isqu&#234;mica e<italic> diabetes mellitus</italic>. Poucos estudos relataram a redu&#231;&#227;o da VFC em pacientes com diabete. Em pacientes diab&#233;ticos sem evid&#234;ncia de neuropatia auton&#244;mica, a redu&#231;&#227;o na VFC durante condi&#231;&#245;es controladas tamb&#233;m foi tem sido relatada<sup>11,24,25</sup>. A VFC anormal em pacientes diab&#233;ticos representa um aumento de risco para arritmias ventriculares, bem como morbidade e mortalidade cardiovascular total<sup>12</sup>. A diminui&#231;&#227;o na VFC em pacientes com DCI e diabete reflete as redu&#231;&#245;es nas modula&#231;&#245;es simp&#225;tica e parassimp&#225;tica do cora&#231;&#227;o. A diminui&#231;&#227;o observada na VFC em pacientes com DCI poderia ser devida &#224; disfun&#231;&#227;o auton&#244;mica como um resultado da isquemia. Uma regula&#231;&#227;o desbalanceada do sistema nervoso auton&#244;mico card&#237;aco &#233; uma das altera&#231;&#245;es patofisiol&#243;gicas importantes na DCI<sup>26,27</sup>. Houve uma diminui&#231;&#227;o mais significante na VFC de pacientes com DCI e neuropatia do que em pacientes sem neuropatia. A VFC pode estar diminu&#237;da em pacientes com diabete devido &#224; neuropatia auton&#244;mica cardiovascular. Tem sido observado que em pacientes adultos com diabete, h&#225; uma disfun&#231;&#227;o do sistema nervoso auton&#244;mico com a longa dura&#231;&#227;o da doen&#231;a<sup>26-29</sup>. A neuropatia auton&#244;mica diab&#233;tica &#233; acompanhada inicialmente por dist&#250;rbios do sistema parassimp&#225;tico, e posteriormente, do sistema simp&#225;tico<sup>28</sup>. Nossa avalia&#231;&#227;o das altera&#231;&#245;es na VFC ap&#243;ia a id&#233;ia de que h&#225; uma diminui&#231;&#227;o na fun&#231;&#227;o auton&#244;mica no inicio do desenvolvimento da diabete e que a diabete leva a um decl&#237;nio progressivo na fun&#231;&#227;o auton&#244;mica e que a VFC pode ser um m&#233;todo eficiente de detec&#231;&#227;o precoce da neuropatia auton&#244;mica diab&#233;tica. </p>
    <p>No presente estudo, a pr&#225;tica da respira&#231;&#227;o abdominal melhorou as medidas da VFC. O presente estudo mostrou que a varia&#231;&#227;o da frequ&#234;ncia card&#237;aca melhorou em pacientes com DCI sem diabete e em pacientes com DCI e diabete que praticaram regularmente exerc&#237;cios de respira&#231;&#227;o. Houve um aumento significante na VFC em controles normais que praticaram a respira&#231;&#227;o diafragm&#225;tica por um ano. A melhora observada na VFC com a t&#233;cnica modificada de respira&#231;&#227;o pode ser devida ao efeito direto da respira&#231;&#227;o sobre o sistema nervoso auton&#244;mico controlando o cora&#231;&#227;o<sup>30</sup>. No corpo humano, a maioria dos par&#226;metros de fun&#231;&#227;o card&#237;aca parece estar ligada ao modo respira&#231;&#227;o. A respira&#231;&#227;o adequada pode influenciar at&#233; mesmo par&#226;metros card&#237;acos sutis, como a fra&#231;&#227;o de eje&#231;&#227;o, press&#227;o a&#243;rtica e press&#227;o arterial pulmonar, pr&#233; e p&#243;s-carga, e at&#233; mesmo a oxigena&#231;&#227;o dos tecidos<sup>31,32</sup>. A respira&#231;&#227;o diafragm&#225;tica pode reduzir a atividade simp&#225;tica ao aumentar o ritmo inibit&#243;rio central<sup>33</sup>. Devido ao aumento do volume tidal durante a respira&#231;&#227;o diafragm&#225;tica profunda, h&#225; uma ativa&#231;&#227;o do reflexo de Hering-Breuer<sup>34</sup>, o qual reduz a sensibilidade quimiorreflexa e pode aumentar o barorreflexo e reduzir a atividade simp&#225;tica<sup>34-36</sup>. Parece que a respira&#231;&#227;o profunda induz a uma diminui&#231;&#227;o generalizada nas vias excitat&#243;rias que regulam o sistema respirat&#243;rio e cardiovascular. Os sistemas respirat&#243;rio e cardiovascular compartilham mecanismos de controle similares e uma altera&#231;&#227;o em um dos sistemas ir&#225; modificar o funcionamento do outro<sup>15,35</sup>. Na doen&#231;a card&#237;aca isqu&#234;mica, h&#225; um aumento na ativa&#231;&#227;o simp&#225;tica e quimiorreflexa e a respira&#231;&#227;o diafragm&#225;tica induziu a uma diminui&#231;&#227;o na ativa&#231;&#227;o simp&#225;tica, o que pode ter aumentado a VFC. Houve uma melhora importante nos par&#226;metros metab&#243;licos estudados ap&#243;s a pr&#225;tica regular de respira&#231;&#227;o diafragm&#225;tica no presente estudo. A diminui&#231;&#227;o na HbA<sub>1C</sub> est&#225; de acordo com estudos pr&#233;vios<sup>37,38</sup>. A diminui&#231;&#227;o na hemoglobina glicada e glicose sangu&#237;nea registrada em pacientes com DCI e diabete e em pacientes com DCI e neuropatia diab&#233;tica indica que os exerc&#237;cios regulares com respira&#231;&#227;o prolongada pode significantemente melhorar a homeostase da glicose e o t&#227;o necess&#225;rio controle glic&#234;mico nesses pacientes. A hiperglicemia e suas consequ&#234;ncias metab&#243;licas relacionadas levam &#224; patog&#234;nese da neuropatia auton&#244;mica na <italic>diabetes mellitus</italic><sup>11,24</sup>. A melhora observada nos par&#226;metros metab&#243;licos poderia ser atribu&#237;da &#224;s mudan&#231;as auton&#244;micas causadas pela respira&#231;&#227;o diafragm&#225;tica, a qual diminuiu a atividade simp&#225;tica<sup>15,35,39,40</sup>. </p>
    <p>O estresse pode ter efeitos negativos na sa&#250;de e o fato de que pacientes com DM tipo 2 possam apresentar risco aumentado de experimentar estresse est&#225; associado com a libera&#231;&#227;o de horm&#244;nios contra-regulat&#243;rios que resultar&#227;o na eleva&#231;&#227;o dos n&#237;veis de glicemia<sup>41</sup>. Al&#233;m disso, o estresse pode interferir com o controle da diabete indiretamente atrav&#233;s de efeitos na dieta, exerc&#237;cio e outros comportamentos de auto-cuidado. O estresse pode ser gerenciado atrav&#233;s do uso de programas comportamentais de gerenciamento de estresse ou atrav&#233;s de medicamentos. Ambos os tipos de interven&#231;&#227;o tem se mostrado eficazes na melhora do controle glic&#234;mico em pacientes com <italic>diabetes mellitus</italic> tipo 2<sup>38,42,43</sup>. O treinamento do gerenciamento de estresse tipicamente inclui relaxamento muscular progressivo com ou sem bioretroalimenta&#231;&#227;o de eletromiografia, imagens mentais, respira&#231;&#227;o diafragm&#225;tica, ioga e instru&#231;&#245;es sobre como modificar as respostas fisiol&#243;gicas, cognitivas e comportamentais ao estresse. Relatos de investigadores estudando o efeito do gerenciamento de estresse sobre o controle glic&#234;mico t&#234;m sido inconsistentes<sup>44,45</sup>, mas v&#225;rios desses estudos tinham baixo poder e outros tinham problemas de projeto. Nosso estudo ap&#243;ia a id&#233;ia de que a interven&#231;&#227;o em forma de pr&#225;tica de respira&#231;&#227;o diafragm&#225;tica profunda levaria a uma melhora no controle glic&#234;mico e tamb&#233;m diminuiria a insufici&#234;ncia auton&#244;mica card&#237;aca em pacientes com DCI e <italic>diabetes mellitus</italic>.</p>
    <p>A atividade f&#237;sica, como uma interven&#231;&#227;o n&#227;o-farmacol&#243;gica, &#233; muito importante em pacientes com s&#237;ndromes metab&#243;licas em quem a ocorr&#234;ncia simult&#226;nea de diabete &#233; acompanhada por um aumento na atividade do sistema nervoso simp&#225;tico. Assim, o efeito da respira&#231;&#227;o diafragm&#225;tica na VFC &#233; principalmente devido &#224; altera&#231;&#227;o no equil&#237;brio entre a atividade do sistema nervoso simp&#225;tico e parassimp&#225;tico sobre o cora&#231;&#227;o. A pr&#225;tica de longo prazo da respira&#231;&#227;o diafragm&#225;tica leva a modifica&#231;&#245;es est&#225;veis no controle auton&#244;mico do cora&#231;&#227;o e resulta no aumento da VFC. Sabe-se que a respira&#231;&#227;o abdominal traz calma interior, relaxamento e aquecimento perif&#233;rico. A respira&#231;&#227;o diafragm&#225;tica &#233; considerada a forma mais saud&#225;vel de respira&#231;&#227;o e &#233; uma das formas mais simples, embora a mais efetiva, das t&#233;cnicas de gerenciamento de estresse<sup>16,32</sup>. A respira&#231;&#227;o diafragm&#225;tica tenta reverter o equil&#237;brio auton&#244;mico em favor do est&#237;mulo parassimp&#225;tico a partir do estimulo simp&#225;tico em pacientes diab&#233;ticos, reduzindo a sintomatologia funcional e promovendo um impacto positivo na sa&#250;de dos indiv&#237;duos<sup>40</sup>. O estudo claramente indica uma melhora no grupo de interven&#231;&#227;o. Isso prova que a respira&#231;&#227;o abdominal &#233; muito mais ben&#233;fica aos pacientes com DCI, DCI com diabete e DCI com neuropatia auton&#244;mica diab&#233;tica. </p>
    <p>
      <bold>Limita&#231;&#245;es do estudo</bold>
    </p>
    <p>H&#225; v&#225;rias limita&#231;&#245;es no estudo. A aus&#234;ncia de dados metab&#243;licos, a falta de medidas cardiovasculares adicionais, o efeito de diferentes composi&#231;&#245;es de alimentos sobre a VFC, a medida da capacidade de exerc&#237;cio (VO<sub>2</sub> pico) e a aus&#234;ncia de dados ecocardiogr&#225;ficos s&#227;o as maiores limita&#231;&#245;es. Uma das dificuldades enfrentadas pelo nosso grupo de pesquisa &#233; a falta de an&#225;lise da VFC no dom&#237;nio de frequ&#234;ncia. Nosso laborat&#243;rio n&#227;o estava especificamente equipado para esse prop&#243;sito, portanto, n&#227;o pudemos conduzir a an&#225;lise de VFC por an&#225;lise espectral, que tem maior sensibilidade e especificidade. Entretanto, a utilidade cl&#237;nica dos achados da VFC a partir dos registros do eletrocardiograma de curta dura&#231;&#227;o &#233; bem estabelecida<sup>46,47</sup>. A influ&#234;ncia do tratamento medicamentoso e sua descontinua&#231;&#227;o sobre a VFC deveriam ser consideradas cuidadosamente. Por raz&#245;es &#233;ticas, n&#243;s n&#227;o descontinuamos o tratamento por um per&#237;odo de tempo extenso. </p>
    <p>Em conclus&#227;o, o estudo confirma que a VFC diminui em pacientes com DCI que tem diabete e que essa diminui&#231;&#227;o da VFC &#233; maior em pacientes com neuropatia diab&#233;tica, indicando um grave desequil&#237;brio auton&#244;mico. A pr&#225;tica regular de respira&#231;&#227;o diafragm&#225;tica aumenta a VFC em controles normais e em pacientes com DCI e DM. Os dados observados deveriam encorajar a pr&#225;tica regular de respira&#231;&#227;o diafragm&#225;tica como terapia n&#227;o-farmacol&#243;gica em pacientes com doen&#231;a card&#237;aca isqu&#234;mica com ou sem diabete e neuropatia diab&#233;tica, junto com o tratamento usual. O objetivo da abordagem seria manter um excelente equil&#237;brio do sistema nervoso auton&#244;mico e regula&#231;&#227;o fisiol&#243;gica da frequ&#234;ncia card&#237;aca. J&#225; que a respira&#231;&#227;o diafragm&#225;tica &#233; uma atividade f&#237;sica f&#225;cil, segura e psicologicamente aceit&#225;vel, consideramos este um achado valioso e como os perfis sociodemogr&#225;ficos dos pacientes no presente estudo foram similares aos de outros estudos internacionais, consideramos que o resultado do presente estudo pode ser aplicado a outras popula&#231;&#245;es. Estudos futuros podem ser necess&#225;rios para estabelecer os benef&#237;cios a longo-prazo da respira&#231;&#227;o diafragm&#225;tica sobre outros m&#233;todos estabelecidos de mensura&#231;&#227;o da VFC em amostras maiores.</p>
    <p>
      <bold>Potencial Conflito de Interesses </bold>
    </p>
    <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
    <p>
      <bold>Fontes de Financiamento</bold>
    </p>
    <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
    <p>
      <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
    </p>
    <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia:</bold>
        </label>
        <p> Nagaraja H S </p>
        <p> School of Medicine, International Medical University </p>
        <p> Plaza Komanwel, Bukit Jalil </p>
        <p> 57000 Kuala Lumpur - Malaysia </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="hsnagaraja@gmail.com">hsnagaraja@gmail.com</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 13/01/08; revisado recebido em 26/04/08; aceito em 08/05/08.</p>
  </body>
  <back>
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  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Effect of diaphragmatic breathing on heart rate variability in ischemic heart disease with diabetes</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: Reduced heart rate variability is associated with an unfavorable prognosis in patients with ischemic heart disease and diabetes. Whether change in breathing pattern can modify the risk factor in these patients has not been definitely proved. OBJECTIVE: To evaluate the effect of diaphragmatic breathing on heart rate variability (HRV) in ischemic heart disease patients with diabetes. METHODS: Study population consisted of 145 randomly selected male patients of which 45 had ischemic heart disease (IHD), 52 had IHD and diabetes (IHD-DM) and the remaining 48 had IHD and diabetic neuropathy (IHD-DN). HRV was assessed by 5 minute-electrocardiogram using the time domain method. The intervention group was divided into compliant and non-compliant groups and follow-up recording was carried out after three months and one year. RESULTS: Baseline recordings showed a significant decrease in HRV in ischemic heart disease (IHD) patients with or without diabetes (p&lt;0.01). IHD patients had higher HRV than IHD patients with diabetes (p&lt;0.01) or diabetic neuropathy (p&lt;0.01). Increase in HRV was observed in patients who practiced diaphragmatic breathing for three months (IHD-DM: p&lt;0.01; IHD-DN: p&lt;0.05) and for one year (IHD-DM: p&lt;0.01; IHD-DN: p&lt;0.01). The HRV significantly decreased after one year in non-compliant patients. The regular practice of diaphragmatic breathing also improved the glycemic index in these patients. CONCLUSION: The regular practice of diaphragmatic breathing significantly improves heart rate variability with a favorable prognostic picture in ischemic heart disease patients who have diabetes. These effects seem to be potentially beneficial in the management of IHD patients with diabetes.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Respiration</kwd>
        <kwd>heart rate</kwd>
        <kwd>heart failure</kwd>
        <kwd>diabetes mellitus</kwd>
        <kwd>myocardial ischemia</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p>
        <fn id="tx-body2">
          <label>
            <bold>Effect of diaphragmatic breathing on heart rate variability in ischemic heart disease with diabetes</bold>
          </label>
          <p>
            <bold>Anupama Bangra Kulur<sup>I</sup>; Nagaraja Haleagrahara<sup>II</sup>; Prabha Adhikary<sup>III</sup>; Jeganathan P. S.<sup>III</sup></bold>
          </p>
        </fn>
      </p>
      <p><sup>I</sup>Faculty of Medicine, University College of Sedaya International, Kuala Lumpur, Malaysia</p>
      <p><sup>II</sup>School of Medicine, International Medical University, Kuala Lumpur, Malaysia</p>
      <p><sup>III</sup>Faculty of Medicine, Kasturba Medical College, Mangalore - India</p>
      <p>Mailing address</p>
      <p>
        <bold>SUMMARY</bold>
      </p>
      <p><bold>BACKGROUND:</bold> Reduced heart rate variability is associated with an unfavorable prognosis in patients with ischemic heart disease and diabetes. Whether change in breathing pattern can modify the risk factor in these patients has not been definitely proved.</p>
      <p><bold>OBJECTIVE:</bold> To evaluate the effect of diaphragmatic breathing on heart rate variability (HRV) in ischemic heart disease patients with diabetes.</p>
      <p><bold>METHODS:</bold> Study population consisted of 145 randomly selected male patients of which 45 had ischemic heart disease (IHD), 52 had IHD and diabetes (IHD-DM) and the remaining 48 had IHD and diabetic neuropathy (IHD-DN). HRV was assessed by 5 minute-electrocardiogram using the time domain method. The intervention group was divided into compliant and non-compliant groups and follow-up recording was carried out after three months and one year.</p>
      <p><bold>RESULTS:</bold> Baseline recordings showed a significant decrease in HRV in ischemic heart disease (IHD) patients with or without diabetes (p&lt;0.01). IHD patients had higher HRV than IHD patients with diabetes (p&lt;0.01) or diabetic neuropathy (p&lt;0.01). Increase in HRV was observed in patients who practiced diaphragmatic breathing for three months (IHD-DM: p&lt;0.01; IHD-DN: p&lt;0.05) and for one year (IHD-DM: p&lt;0.01; IHD-DN: p&lt;0.01). The HRV significantly decreased after one year in non-compliant patients. The regular practice of diaphragmatic breathing also improved the glycemic index in these patients.</p>
      <p><bold>CONCLUSION:</bold> The regular practice of diaphragmatic breathing significantly improves heart rate variability with a favorable prognostic picture in ischemic heart disease patients who have diabetes. These effects seem to be potentially beneficial in the management of IHD patients with diabetes.</p>
      <p><bold>Key Words:</bold> Respiration; heart rate; heart failure; diabetes mellitus; myocardial ischemia.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>Heart rate variability (HRV) is the natural rise and fall of the heart rate in response to breathing, blood pressure, hormones and emotions<sup>1</sup>. It is seen as reflective and predictive of general health and overall psychological illness. HRV represents one of the most promising markers of autonomic activity<sup>2</sup>. HRV impairment has been observed in many clinical scenarios, including autonomic neuropathy, heart transplantation, congestive heart failure, myocardial infarction and other cardiac and non-cardiac diseases<sup>3</sup>. Several studies have demonstrated reduced heart rate variability in patients with ischemic heart disease<sup>4,5</sup>. The mechanism of HRV reduction in ischemic heart disease is not known<sup>5,6</sup>. Intermittent or chronic ischemia may play an important role, as it has been demonstrated that ischemic episodes are associated with acutely reduced vagal tone<sup>7</sup>.</p>
      <p>Diabetic autonomic neuropathy affects about 40% of all diabetic patients and in its severe form offers a very poor prognosis<sup>8</sup>. As HRV reflects the degree of autonomic control of the heart, it is widely used for the diagnosis of the autonomic dysfunctions in non-cardiac diseases on the assumption that, if such a dysfunction in the heart is identified, it is a sign of a more widespread autonomic neuropathy affecting all organs<sup>9</sup>. It has been observed that cardiovascular autonomic diabetic neuropathy is associated with the loss of heart rate variability. In diabetes mellitus-associated neuropathy, characterized by the alteration of the small nerve fibers, a reduction in time domain parameters of the HRV seems not only to carry a negative prognostic value, but also to precede the clinical expression of autonomic neuropathy<sup>10,11</sup>.</p>
      <p>Because decreased HRV is associated with an adverse outcome, researchers thought that increasing HRV would improve survival rates. Many of the interventions associated with decreased mortality such as exercise practice, cessation of smoking and drug therapy are also associated with increased HRV<sup>10-12</sup>. Respiratory activity is known to influence heart rate through both anatomical and physiological mechanisms<sup>13</sup>. Respiratory restraining using the slow-breathing technique is a useful adjunct therapy for cardiorespiratory control<sup>14</sup>. According to Chacko et al<sup>15</sup>, slow breathing at 6 cycles per minute increases the baroreflex sensitivity in normal subjects and patients with heart failure<sup>15</sup>. Slow abdominal breathing is known to decrease the sympathetic nervous system activity<sup>16</sup>. Abdominal breathing has been shown to reduce the occurrence of coronary events in individuals that have already suffered a heart attack. This type of breathing is known to reduce the tension in the respiratory muscle, to decrease functional symptomatology and to reduce anxiety and promote a feeling of relaxation<sup>17</sup>. Recent evidence suggests that slow breathing lowers blood pressure in patients with mild and moderate hypertension and those with resistant hypertension, without changes in medication<sup>18</sup>.There have been hardly any studies on the effect of diaphragmatic breathing maneuvers on heart rate variability in diabetic patients. Hence, the aim of this study was to determine the HRV in ischemic heart disease patients who have diabetes with or without autonomic neuropathy. Our research hypothesis was that the regular practice of diaphragmatic breathing would improve heart rate variability in ischemic heart disease patients with type 2 diabetes mellitus. </p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>The study group consisted of 145 randomly selected male subjects from Kasturba Medical College Hospital, of Manipal University, India, with an age range of 40 -70 years. The patients' group consisted of 45 ischemic heart disease patients without diabetes, 52 patients with IHD and type 2 diabetes mellitus and the remaining 48 patients with IHD and diabetic autonomic neuropathy. After the inclusion and exclusion criteria were applied, patients were interviewed and general physical examination was carried out and the subjects' data on the clinical profile, pharmacological treatment and epidemiological profile were collected. Height, weight, waist-hip ratio, blood pressure, heart rate, respiratory rate and complete systemic examination were performed. A 12-lead electrocardiogram (ECG) was recorded and the findings were recorded. The glucose dehydrogenase method was used to measured glucose levels in the fasting blood samples. Glycosylated hemoglobin (HbA<sub>1C</sub>) was measured by the immunoturbidimetric method.</p>
      <p>Patients diagnosed with angina, myocardial infarction or myocardial infarctions with cardiac failure that had diabetes mellitus were included in the study group. Exclusion criteria were the following; patients with valvular heart disease, obstructive lung disease, asthma, cardiomyopathies, atrial fibrillation, and bundle branch block. The diagnosis of ischemic heart disease was documented by; ECG evidence of prior myocardial infarction, ECG evidence of ST-depression, chest pain on a treadmill test within the past six months, coronary angiography showing &gt;60% stenosis of one major coronary artery. Diabetes mellitus patients were classified as having diabetes on the basis of history, regardless of disease duration or need for anti-diabetic agents. Diabetes was defined as fasting glucose <underline>&gt;</underline> 7.0 mmol/L. Diabetic neuropathy was established if two or more standard cardiovascular reflex tests of autonomic function were abnormal<sup>19,20</sup>. The autonomic function tests included </p>
      <p>I) beat-to-beat measurement of heart rate variation during timed ventilation, </p>
      <p>II) postural heart rate response (30:15 ratio), </p>
      <p>III) heart rate variation during a standardized Valsalva maneuver and </p>
      <p>IV) hemodynamic response to assumption of upright posture. Sixty age-matched healthy subjects were used as the control group. They had no symptoms of any disease, were drug-free and had normal electrocardiogram results at rest. All the study groups were well balanced with regard to the demographic data and pharmacological treatment. All the subjects were instructed about the protocol and gave their informed consent to participate in the study. The study was approved by the Institutional Ethical Committee and complies with all the principles postulated in the Declaration of Helsinki in 1983. </p>
      <p>
        <bold>Analysis of heart rate variability (HRV)</bold>
      </p>
      <p>Deep breathing heart rate test<sup>21-23</sup> was conducted with the subject in the supine position during standard electrocardiogram recording. The subjects were taught to breathe at a rate of 6 respiratory cycles per minute; 5s for each inhalation and 5s for each exhalation. The electrocardiogram was recorded continuously at 25mm/second for five minutes while the patients breathed as instructed. Beat-to-beat alterations in heart rate were evaluated by the time-domain method. The R-R interval was measured in each respiratory cycle and an average R-R interval was considered for the measurement of HRV. The variability in the heart rate was calculated as the difference between the shortest and the longest R-R intervals. Deep breathing HRV test was chosen as a short bedside test based on the experience achieved in testing autonomic nervous control of the heart in patients with diabetes mellitus. A test result was pre-specified as normal if there was a difference of ten beats or more per minute between the slowest and the fastest heart rate.</p>
      <p>
        <bold>Diaphragmatic Breathing</bold>
      </p>
      <p>Patients and the control subjects were taught diaphragmatic breathing (abdominal breathing) by a hospital physiotherapist. They were asked to perform abdominal breathing while lying in the supine position. They were asked to inhale slowly and deeply through the nose into the bottom of the lungs, i.e., sending the air, as deep into the lungs as possible. The chest moves slightly while the abdomen expands and the diaphragm moves downwards. After taking a full breath, the patients were asked to hold it for a moment and then to exhale slowly through controlled expiration. </p>
      <p>The breathing exercise intervention group was divided prospectively into those that were willing to do the exercises regularly (compliant group; 80 patients and 32 controls) and those that were not (non-compliant group; 65 patients and 28 controls). Patients and controls in the compliant group were urged to perform ten slow full diaphragmatic breathing exercises at a time while lying supine with a rest interval of 30 s to one minute and then start up again. They were advised to practice the diaphragmatic breathing for 10-15 min, twice daily (in the morning and in the evenings). Subjects were asked to practice this breathing technique for one year and report for observations. Patients and the control subjects were followed on an outpatient basis for a period of 12 months, with visits at one-month intervals. During the visit, the physiotherapist interviewed the subjects and recorded the details about their breathing exercise regimen. They were regularly motivated to continue the breathing exercise. The subjects were instructed at the hospital by a clinician on the management of ischemic heart disease and type 2 diabetes mellitus and the role of breathing exercises in the management of diseases. Each subject received a notebook with instructions and benefits of breathing exercises and illustrations of abdominal breathing. Subjects were advised to note down their drug therapy, diet and other physical activities during the study period. During the entire 12 months of follow up period all the subjects included in the study were closely supervised by a clinician and a physiotherapist. Both compliant and non-compliant group subjects were reported for the follow up recordings. During the follow-up period of three months and twelve months, heart rate variability, fasting blood glucose, body weight and glycated hemoglobin data were recorded. The subjects' physical activities, body weight, drug therapy, diets etc., were checked and any problems observed during the breathing exercises were discussed. </p>
      <p>All the results were expressed as mean &#177; standard error of mean or numbers and percentages. The statistical package for social sciences (SPSS, version 11) was used for the statistical analysis. The Mann-Whitney U test was used to compare various parameters between different groups. The Wilcoxon signed-rank test was employed to compare the results between baseline and follow-up recordings. To study whether the diaphragmatic breathing alone influenced HRV, a stepwise multiple regression test was used. P values less than 0.05 were considered significant in all the statistical analysis. </p>
      <p>
        <bold>Results</bold>
      </p>
      <p>Clinical characteristics of the patients are shown in <xref ref-type="table" rid="tab01-body2">Table 1</xref>. The three study groups and the control group were well-balanced concerning demographic data. The study groups did not significantly differ regarding age, duration of diabetes and medication use. There was a significant decrease in the heart rate variability in IHD patients without diabetes (p&lt;0.01) when compared to the healthy controls. IHD patients with diabetes mellitus (p&lt;0.01) and with neuropathy also had a significantly reduced (p&lt;0.01) heart rate variability compared to controls. Ischemic heart disease patients without diabetes had a significantly higher HRV (p&lt;0.05) than IHD patients with diabetes (DM) or diabetic neuropathy (DN). There was no significant difference in HRV between IHD with DM or with DN groups. HbA<sub>1C</sub> and fasting blood glucose levels were significantly higher in IHD with diabetes (p&lt;0.01) and IHD with diabetic neuropathy (p&lt;0.01) groups when compared to control and IHD groups (<xref ref-type="table" rid="tab02-body2">table 2</xref>).</p>
      <table-wrap id="tab01-body2">
        <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt01-en.jpg"/></table-wrap>
      <table-wrap id="tab02-body2">
        <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt02-en.jpg"/></table-wrap>
      <p>As shown in <xref ref-type="table" rid="tab03-body2">Table 3</xref>, patients with IHD without diabetes and those with diabetes with or without neuropathy, all showed a significant increase in HRV (p&lt;0.01) at the three -month and one-year follow-up after diaphragmatic breathing exercises. A more statistically significant increase in HRV was recorded (p&lt;0.01- for all groups) after one year of follow-up, when compared to their baseline recordings in all the study groups. Increase in HRV after the follow-up was significantly higher (p&lt;0.01) in IHD with diabetes group than IHD with diabetic neuropathy group. The regular practice of diaphragmatic breathing increased heart rate variability in control subjects also after one year (p&lt;0.01) (<xref ref-type="table" rid="tab03-body2">Table 3</xref>). A significant decrease in HbA<sub>1C</sub> (p&lt;0.01) and blood glucose level (p&lt;0.01) was seen after 3 and 12 month-follow up recording in the compliant group. Even though the levels of HbA<sub>1C</sub> and blood glucose were significantly higher (p&lt;0.01) than in the control and IHD groups, the regular practice of diaphragmatic breathing significantly decreased these metabolic parameters after the 12-month follow-up, when compared to baseline levels (<xref ref-type="table" rid="tab04-body2">Table 4</xref>). </p>
      <table-wrap id="tab03-body2">
        <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt03-en.jpg"/></table-wrap>
      <table-wrap id="tab04-body2">
        <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt04-en.jpg"/></table-wrap>
      <p><xref ref-type="table" rid="tab05-body2">Table 5</xref> shows the heart rate variability recorded in non-compliant controls and IHD patients after three months and twelve months. There was no significant difference in HRV after the three-month follow-up in all non-compliant groups. There was a significant decrease in HRV in IHD patients without diabetes (p&lt;0.01), IHD patients with DM (p&lt;0.01) and IHD patients with diabetic neuropathy (p&lt;0.01) after the one-year follow-up period (<xref ref-type="table" rid="tab05-body2">table 5</xref>). No significant difference in the metabolic parameters (HbA<sub>1C</sub> and blood sugar) was recorded after the first follow up period, but HbA<sub>1C</sub> increased significantly after one year of follow-up in IHD patients with diabetic neuropathy (p&lt;0.01). Blood glucose levels increased significantly in non-compliant IHD patients without DM (p&lt;0.05), IHD with DM (p&lt;0.01) and IHD with DN (p&lt;0.01), indicating that the disease condition worsened without diaphragmatic breathing (<xref ref-type="table" rid="tab06-body2">table 6</xref>).</p>
      <table-wrap id="tab05-body2">
        <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt05-en.jpg"/></table-wrap>
      <table-wrap id="tab06-body2">
        <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt06-en.jpg"/></table-wrap>
      <p>When heart rate variability was compared between the compliant and non-compliant groups after one-year follow-up, a more significant increase was recorded in all the groups including controls (p&lt;0.01) (<xref ref-type="table" rid="tab07-body2">Table 7</xref>). In the non-compliant groups, there was a significant decrease in HRV among IHD patients with DM and DN (p&lt;0.01), when compared to compliant patients. </p>
      <table-wrap id="tab07-body2">
        <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt07-en.jpg"/></table-wrap>
      <p>Multiple regression analysis indicated that breathing alone accounted for a 58.8% (R=0.588) variation in HRV after one year follow-up. When other predictive variables were included, the contribution of breathing increased to 72% (R=0.725). Diaphragmatic breathing alone showed the greater contribution for the observed changes in HRV. The coefficient of diaphragmatic breathing was the highest, showing the maximum contribution when compared to other predictors such as medication, duration of diabetes, age etc.</p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>The present study showed that there was a significant decrease in heart rate variability in ischemic heart disease patients and IHD patients who had diabetes. Few studies have reported the reduction of HRV in diabetes. In diabetic patients without evidence of autonomic neuropathy, the reduction in heart rate variability during controlled conditions has also been reported<sup>11,24,25</sup>. Abnormal heart rate variability in diabetes represents an increased risk for ventricular arrhythmias, as well as total cardiovascular morbidity and mortality<sup>12</sup>. The decrease in HRV in IHD patients with diabetes reflects the reductions in both sympathetic and parasympathetic modulation of the heart. The observed decrease in heart rate variability in IHD patients could be due to the autonomic dysfunction as a result of ischemia. Imbalanced regulation of the cardiac autonomic nervous system is one of the important pathophysiological changes in IHD<sup>26,27</sup>. There was a more significant decrease in HRV in IHD patients with neuropathy than the patients without neuropathy. The heart rate variability may be diminished in patients with diabetes due to cardiovascular autonomic neuropathy. It has been observed that in adult patients with diabetes, there is dysfunction of the autonomic nervous system with the long duration of the disease<sup>26-29</sup>. Diabetic autonomic neuropathy is accompanied at first by disorders of the parasympathetic and later, of the sympathetic system<sup>28</sup>. Our assessment of the HRV changes supports the view that there is a decrease in autonomic function early in the development of diabetes and that diabetes leads to a progressive decline in autonomic function and that heart rate variability may be an efficient method for early detection of diabetic autonomic neuropathy.</p>
      <p>In this study, the practice of abdominal breathing improved the heart rate variability measures. The present study showed that HRV improved in non-DM IHD patients and DM &#150;IHD patients who practiced regular breathing exercises. There was a significant increase in HRV in normal control subjects who practiced diaphragmatic breathing for one year. The observed improvement in HRV with the modified breathing technique could be due to the direct effect of breathing on the autonomic nervous system controlling the heart<sup>30</sup>. In the human body, most parameters of the cardiac function have been shown to be mode-locked to breathing. Proper breathing could influence even subtle cardiac parameters such as ejection fraction, aortic pressure, and pulmonary arterial pressure, preload and afterload and even tissue oxygenation<sup>31,32</sup>. Diaphragmatic breathing may reduce sympathetic activity by enhancing central inhibitory rhythm<sup>33</sup>. Due to increased tidal volume during deep diaphragmatic breathing, there is the activation of the Hering-Breur reflex<sup>34</sup> which reduces the chemoreflex sensitivity and might enhance the baroreflex and reduce the sympathetic activity<sup>34-36</sup>. It seems that deep breathing induces generalized decrease in the excitatory pathways regulating respiratory and cardiovascular system. The respiratory and cardiovascular systems share similar control mechanisms and alterations in one system will modify the functioning of the other<sup>15,35</sup>. In ischemic heart disease, there is increased sympathetic and chemoreflex activation and diaphragmatic breathing induced a reduction in the sympathetic activation, which might have increased the HRV. There was a significant improvement in the metabolic parameters studied after the regular practice of diaphragmatic breathing in the present study. The decrease in HbA<sub>1C</sub> is in agreement with the earlier reports<sup>37,38</sup>. The decrease in glycated hemoglobin and blood glucose recorded in IHD patients with diabetes and diabetic neuropathy indicates that regular prolonged breathing exercises can significantly improve the blood glucose homeostasis and the much-needed glycemic control among these patients. Hyperglycemia and its related metabolic consequences leads to the pathogenesis of autonomic neuropathy in diabetes<sup>11,24</sup>. The observed improvement in metabolic parameters could be attributed to the autonomic changes brought about by diaphragmatic breathing, which decreased the sympathetic activity<sup>15,35,39,40</sup>. </p>
      <p>Stress may have negative effects on health and the fact that patients with type 2 diabetes may be at increased risk for the experience of stress is associated with the release of counter-regulatory hormones that will result in elevated blood glucose levels<sup>41</sup>. In addition, stress can disrupt diabetes control indirectly through effects on diet, exercise, and other self-care behaviors. Stress can be managed through the use of behavioral stress management programs or through medication use. Both types of interventions have been reported to improve glycemic control in patients with type 2 diabetes<sup>38,42,43</sup>. Stress management training typically includes progressive muscle relaxation with or without electromyography biofeedback, mental imagery, diaphragmatic breathing, yoga and instructions on how to modify the physiological, cognitive and behavioral responses to stress. Reports from researchers investigating the effect of stress management on glycemic control have been inconsistent<sup>44,45</sup>, but several of these studies were underpowered, and others had design problems. Our study supports the view that that intervention in the form of deep diaphragmatic breathing practice would improve the glycemic control and also decrease the cardiac autonomic impairment in IHD patients with diabetes mellitus.</p>
      <p>Physical activity, as a non-pharmacological intervention, is very important in patients with the metabolic syndromes in whom the simultaneous occurrence of diabetes is accompanied by an increased activity in the sympathetic nervous system. Thus, the effect of diaphragmatic breathing on the heart rate variability is mainly due to the alteration in the balance between the sympathetic and parasympathetic nervous systems activity on the heart. Long-term practice of diaphragmatic breathing lead to stable modifications in the autonomic control of the heart and resulted in increased heart rate variability. Abdominal breathing is known to evoke internal quieting, relaxation and peripheral warming. Diaphragmatic breathing is considered as the healthiest form of breathing and it is one of the simplest, yet most powerful, stress management techniques<sup>16,32</sup>. Diaphragmatic breathing tries to reverse the autonomic balance in favor of the parasympathetic stimulation from the sympathetic stimulation in diabetic patients, reducing the functional symptomatology and promoting a positive impact on individual health<sup>40</sup>. The study clearly indicates a positive improvement in the intervention group. This proves that abdominal breathing is much more beneficial to the patients with ischemic heart disease and IHD patients with diabetes and diabetes autonomic neuropathy. </p>
      <p>
        <bold>Study limitations</bold>
      </p>
      <p>There are several limitations in this study. The absence of metabolic data, lack of accompanying cardiovascular measures, the effect of different meal compositions on HRV, measurement of exercise capacity (peak VO2), and absence of echocardiographic data are the major limitations. One of the difficulties faced by our research group is the lack of frequency-domain HRV analysis. Our laboratory was not specifically equipped for this purpose; hence, we could not conduct the HRV analysis by spectral analysis, which has higher sensitivity and specificity. However, the clinical usefulness of the heart rate variability findings from short-term ECG recordings is well-established<sup>46,48</sup>. The influence of drug treatment and its withdrawal on heart rate variability should be carefully considered. For ethical reasons, we did not discontinue the treatment for an extended period of time.</p>
      <p>In conclusion, the study confirms that heart rate variability decreases in patients with ischemic heart disease who have diabetes and that this decrease is higher in patients with diabetic neuropathy, indicating severe autonomic imbalance. The regular practice of diaphragmatic breathing increases heart rate variability in normal control subjects and in ischemic heart disease patients with diabetes. The observed data should encourage the regular practice of diaphragmatic breathing as a non-pharmacological therapy in patients with ischemic heart disease with or without diabetes and diabetic neuropathy, along with the regular treatment. The aim of the approach would be to maintain an optimal autonomic nervous system balance and physiological heart rate regulation. As the diaphragmatic breathing is an easy, safe and psychologically acceptable physical activity, we consider this as a valuable finding and considering that the socio-demographic profile of the patients in this study were similar to other international studies, we believe the results of the present study can be applied to other populations. Further studies may be required to establish the long-term benefits of diaphragmatic breathing on other established methods of HRV measurements in larger populations.</p>
      <p>
        <bold>Potential Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>Sources of Funding</bold>
      </p>
      <p>There were no external funding sources for this study.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This study is not associated with any post-graduation program.</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
  <sub-article article-type="translation" id="TRes" xml:lang="es">
    <front-stub>
      <article-categories/>
      <title-group>
        <article-title xml:lang="es">Efecto de la respiraci&#243;n diafragm&#225;tica sobre la variabilidad de la frecuencia cardiaca en la enfermedad cardiaca isqu&#233;mica con diabetes</article-title>
      </title-group>
      <abstract xml:lang="es">
        <p>FUNDAMENTO: La disminuci&#243;n de la variabilidad de la frecuencia cardiaca (VFC) est&#225; asociada a un pron&#243;stico desfavorable en pacientes con enfermedades cardiaca isqu&#233;mica (DCI) y diabetes. Todav&#237;a no se aprob&#243; en definitivo si el cambio en el est&#225;ndar respiratorio puede modificar el factor de riesgo en esos pacientes. OBJETIVO: Evaluar el efecto de la respiraci&#243;n diafragm&#225;tica sobre la VFC en pacientes diab&#233;ticos con DCI. M&#201;TODOS: La poblaci&#243;n del estudio consisti&#243; en 145 pacientes del sexo masculino seleccionados al azar, de los cuales 45 presentaban DCI, 52 presentaban DCI y diabetes (DCI-DM) y 48 presentaban DCI y neuropat&#237;a diab&#233;tica (DCI-ND). La VFC se evalu&#243; a trav&#233;s de ECG de 5 minutos con el empleo del m&#233;todo de dominio de tiempo. El grupo de intervenci&#243;n se dividi&#243; en grupo adherente y no-adherente y se registr&#243; el seguimiento tras tres meses y un a&#241;o. RESULTADOS: La evaluaci&#243;n basal revel&#243; una disminuci&#243;n significante en VFC en los pacientes con enfermedades cardiaca isqu&#233;mica con o sin diabetes (p&lt;0,01). Los pacientes con DCI presentaban VFC m&#225;s alta que los pacientes con DCI-DM (p&lt;0,01) y DCI-ND (p&lt;0,01). Un aumento en la VFC se observ&#243; en pacientes que practicaron respiraci&#243;n diafragm&#225;tica por tres meses (DCI-DM: p&lt;0,01; DCI-ND: p&lt;0,05) y por un a&#241;o (DCI-DM: p&lt;0,01; DCI-ND: p&lt;0,01). La VFC disminuy&#243; significantemente tras un a&#241;o en pacientes no-adherentes. La pr&#225;ctica regular de respiraci&#243;n diafragm&#225;tica tambi&#233;n mejor&#243; el &#237;ndice gluc&#233;mico en esos pacientes. CONCLUSI&#211;N: La pr&#225;ctica regular de respiraci&#243;n diafragm&#225;tica mejora de forma significante la VFC en una direcci&#243;n pron&#243;sticamente favorable en pacientes con DCI y diabetes. Esos efectos parecen ser potencialmente ben&#233;ficos en el manejo de esos pacientes.</p>
      </abstract>
      <kwd-group xml:lang="es">
        <kwd>Respiraci&#243;n</kwd>
        <kwd>frecuencia cardiaca</kwd>
        <kwd>insuficiencia cardiaca</kwd>
        <kwd>diabetes mellitus</kwd>
        <kwd>isquemia mioc&#225;rdica</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ART&#205;CULO ORIGINAL</bold>
      </p>
      <p><undefined id="tx-body3"/>Efecto de la respiraci&#243;n diafragm&#225;tica sobre la variabilidad de la frecuencia cardiaca en la enfermedad cardiaca isqu&#233;mica con diabetes</p>
      <p>
        <bold>Anupama Bangra Kulur<sup>I</sup>; Nagaraja Haleagrahara<sup>II</sup>; Prabha Adhikary<sup>III</sup>; Jeganathan P. S.<sup>III</sup></bold>
      </p>
      <p><sup>I</sup>Faculty of Medicine, University College of Sedaya International, Kuala Lumpur, Malaysia</p>
      <p><sup>II</sup>School of Medicine, International Medical University, Kuala Lumpur, Malaysia</p>
      <p><sup>III</sup>Faculty of Medicine, Kasturba Medical College, Mangalore, &#205;ndia</p>
      <p>Correspondencia</p>
      <p>
        <bold>RESUMEN</bold>
      </p>
      <p><bold>FUNDAMENTO:</bold> La disminuci&#243;n de la variabilidad de la frecuencia cardiaca (VFC) est&#225; asociada a un pron&#243;stico desfavorable en pacientes con enfermedades cardiaca isqu&#233;mica (DCI) y diabetes. Todav&#237;a no se aprob&#243; en definitivo si el cambio en el est&#225;ndar respiratorio puede modificar el factor de riesgo en esos pacientes.</p>
      <p><bold>OBJETIVO:</bold> Evaluar el efecto de la respiraci&#243;n diafragm&#225;tica sobre la VFC en pacientes diab&#233;ticos con DCI.</p>
      <p><bold>M&#201;TODOS:</bold> La poblaci&#243;n del estudio consisti&#243; en 145 pacientes del sexo masculino seleccionados al azar, de los cuales 45 presentaban DCI, 52 presentaban DCI y diabetes (DCI-DM) y 48 presentaban DCI y neuropat&#237;a diab&#233;tica (DCI-ND). La VFC se evalu&#243; a trav&#233;s de ECG de 5 minutos con el empleo del m&#233;todo de dominio de tiempo. El grupo de intervenci&#243;n se dividi&#243; en grupo adherente y no-adherente y se registr&#243; el seguimiento tras tres meses y un a&#241;o.</p>
      <p><bold>RESULTADOS:</bold> La evaluaci&#243;n basal revel&#243; una disminuci&#243;n significante en VFC en los pacientes con enfermedades cardiaca isqu&#233;mica con o sin diabetes (p&lt;0,01). Los pacientes con DCI presentaban VFC m&#225;s alta que los pacientes con DCI-DM (p&lt;0,01) y DCI-ND (p&lt;0,01). Un aumento en la VFC se observ&#243; en pacientes que practicaron respiraci&#243;n diafragm&#225;tica por tres meses (DCI-DM: p&lt;0,01; DCI-ND: p&lt;0,05) y por un a&#241;o (DCI-DM: p&lt;0,01; DCI-ND: p&lt;0,01). La VFC disminuy&#243; significantemente tras un a&#241;o en pacientes no-adherentes. La pr&#225;ctica regular de respiraci&#243;n diafragm&#225;tica tambi&#233;n mejor&#243; el &#237;ndice gluc&#233;mico en esos pacientes.</p>
      <p><bold>CONCLUSI&#211;N:</bold> La pr&#225;ctica regular de respiraci&#243;n diafragm&#225;tica mejora de forma significante la VFC en una direcci&#243;n pron&#243;sticamente favorable en pacientes con DCI y diabetes. Esos efectos parecen ser potencialmente ben&#233;ficos en el manejo de esos pacientes.</p>
      <p><bold>Palabras clave:</bold> Respiraci&#243;n, frecuencia cardiaca, insuficiencia cardiaca, diabetes mellitus, isquemia mioc&#225;rdica.</p>
      <p>
        <bold>Introducci&#243;n</bold>
      </p>
      <p>La variabilidad de la frecuencia cardiaca (VFC) es la natural elevaci&#243;n y disminuci&#243;n de la frecuencia cardiaca en respuesta a la respiraci&#243;n, presi&#243;n arterial, hormonas y emociones<sup>1</sup>. Se la ve como un indicador reflectivo y predictivo de la salud y de la enfermedad psicol&#243;gica en general. La VFC representa un de los marcadores m&#225;s promisorio de la actividad auton&#243;mica<sup>2</sup>. Se ha observado una VFC deficiente en muchos cuadros cl&#237;nicos, incluyendo la neuropat&#237;a auton&#243;mica, transplante card&#237;aco, insuficiencia cardiaca congestiva, infarto de miocardio y otras enfermedades cardiacas y no-cardiacas<sup>3</sup>. Varios estudios han demostrado reducci&#243;n en la VFC en pacientes con enfermedad cardiaca isqu&#233;mica (DCI)<sup>4,5</sup>. Sin embargo, no se conoce a&#250;n el mecanismo de la reducci&#243;n de la VFC en la enfermedad cardiaca isqu&#233;mica<sup>5,6</sup>. La isquemia cr&#243;nica o intermitente puede tener un rol importante, ya que se evidenci&#243; que episodios isqu&#233;micos est&#225;n asociados al tono vagal reducido de forma aguda<sup>7</sup>.</p>
      <p>La neuropat&#237;a auton&#243;mica diab&#233;tica afecta aproximadamente el 40% de todos los pacientes diab&#233;ticos y en su forma severa, ofrece un pron&#243;stico malo<sup>8</sup>. Como la VFC refleja el grado de control auton&#243;mico del coraz&#243;n, se la utiliza ampliamente para el diagn&#243;stico de las disfunciones auton&#243;micas en enfermedades no-cardiacas, consider&#225;ndose que, si dicha disfunci&#243;n cardiaca fuera identificada, es un signo de una neuropat&#237;a auton&#243;mica m&#225;s generalizada, afectando todos los &#243;rganos<sup>9</sup>. Se ha observado que la neuropat&#237;a auton&#243;mica diab&#233;tica cardiovascular est&#225; asociada a la p&#233;rdida de la variabilidad de la frecuencia cardiaca. En la neuropat&#237;a asociada a la diabetes mellitus, caracterizada por la alteraci&#243;n de las peque&#241;as fibras nerviosas, una reducci&#243;n en los par&#225;metros del dominio de tiempo de la VFC parece no s&#243;lo tener un valor pron&#243;stico negativo, sino tambi&#233;n preceder la expresi&#243;n cl&#237;nica de la neuropat&#237;a auton&#243;mica<sup>10,11</sup>.</p>
      <p>Debido al hecho de la disminuci&#243;n de la VFC estar asociada a un resultado adverso, los investigadores concluyeron que el aumento en la VFC aumentar&#237;a tambi&#233;n las tasas de supervivencia.</p>
      <p>Muchas de las intervenciones asociadas a la disminuci&#243;n de la mortalidad, como pr&#225;ctica de ejercicios, abandono del h&#225;bito de fumar, terapia medicamentosa, tambi&#233;n est&#225;n asociadas al aumento de la VFC<sup>10-12</sup>. Se sabe que la actividad respiratoria influencia la frecuencia cardiaca a trav&#233;s de mecanismos fisiol&#243;gicos y anat&#243;micos<sup>13</sup>. </p>
      <p>Refrenar la respiraci&#243;n por medio de la t&#233;cnica de respiraci&#243;n lenta es una terapia adjunta &#250;til para el control cardiorrespirat&#243;rio<sup>14</sup>. De acuerdo con Chacko et al<sup>15</sup> la respiraci&#243;n lenta a 6 ciclos por minuto aumenta la sensibilidad barorrefleja en individuos normales y en pacientes con insuficiencia cardiaca<sup>15</sup>. Se sabe que la respiraci&#243;n abdominal lenta disminuye la actividad del sistema nervioso simp&#225;tico<sup>16</sup> y se ha evidenciado que la respiraci&#243;n abdominal reduce la recurrencia de eventos coronarios en individuos que ya sufrieron un infarto. Se sabe que ese tipo de respiraci&#243;n reduce la tensi&#243;n en el m&#250;sculo respiratorio, la sintomatolog&#237;a funcional y la ansiedad, adem&#225;s de promover una sensaci&#243;n de relajaci&#243;n<sup>17</sup>. Evidencias recientes sugieren que la respiraci&#243;n lenta disminuye la presi&#243;n arterial en pacientes con hipertensi&#243;n leve y moderada y en pacientes con hipertensi&#243;n resistente, sin cambios en la medicaci&#243;n<sup>18</sup>. </p>
      <p>Hay pocos estudios sobre el efecto de las maniobras de respiraci&#243;n diafragm&#225;tica sobre la VFC en pacientes con diabetes mellitus. De esa manera, el presente estudio se llev&#243; a cabo con el principal objetivo de determinar la VFC en pacientes con DCI y diabetes, con o sin neuropat&#237;a auton&#243;mica. Nuestra hip&#243;tesis de estudio fue que la pr&#225;ctica regular de respiraci&#243;n diafragm&#225;tica mejora la VFC en pacientes con DCI y diabetes. </p>
      <p>
        <bold>M&#233;todos</bold>
      </p>
      <p>El grupo de estudio estaba conformado por 145 individuos del sexo masculino, seleccionados al acaso, en el Kasturba Medical College Hospital, de la Universidad Manipal, &#205;ndia, cuya edad variaba de 40 a 70 a&#241;os. El grupo de pacientes ten&#237;a 45 pacientes con DCI sin diabetes, 52 pacientes con DCI y diabetes mellitus tipo 2 y 48 pacientes remanentes con DCI y neuropat&#237;a auton&#243;mica diab&#233;tica. Tras aplicarse los criterios de inclusi&#243;n y exclusi&#243;n, se entrevistaron a los pacientes y se los sometieron a examen f&#237;sico general. Se recolectaron los datos de los individuos sobre el perfil cl&#237;nico, tratamiento farmacol&#243;gico y perfil epidemiol&#243;gico. Se obtuvieron altura, peso, raz&#243;n cintura-cadera, presi&#243;n arterial, frecuencia cardiaca y frecuencia respiratoria, y se llev&#243; a cabo un estudio sist&#233;mico completo. Un electrocardiograma (ECG) de 12 derivaciones se llev&#243; a cabo y los hallazgos se registraron. Se midi&#243; la glucemia de ayuno en la muestra de sangre por medio del m&#233;todo de glucosa deshidrogenasa. La hemoglobina glicosilada (HbA<sub>1C</sub>) se midi&#243; con el m&#233;todo inmunoturbidim&#233;trico. </p>
      <p>Pacientes diagnosticados con angina, infarto de miocardio o infarto de miocardio con insuficiencia cardiaca y diabetes se incluyeron en el grupo de estudio. Los criterios de exclusi&#243;n fueron los que siguen: pacientes con enfermedad cardiaca valvular, enfermedad pulmonar obstructiva, asma, cardiomiopat&#237;as, fibrilaci&#243;n atrial y bloqueo de rama. El diagn&#243;stico de la DCI fue documentado por evidencia de ECG de infarto del miocardio previo, evidencia de ECG de depresi&#243;n del segmento ST, dolor tor&#225;cico en la prueba de esfuerzo en los &#250;ltimos seis meses, angiograf&#237;a coronaria con &gt; 60% de estenosis en una arteria coronaria principal. Se clasificaron a pacientes con diabetes mellitus (DM) como portadores de diabetes con base en el hist&#243;rico, independientemente de la duraci&#243;n de la enfermedad o necesidad de uso de agentes antidiab&#233;ticos. La DM se defini&#243; como glucemia de ayuno <underline>&gt;</underline> 7,0 mmol/l. La neuropat&#237;a diab&#233;tica se estableci&#243; cuando dos o m&#225;s pruebas reflejas cardiovasculares est&#225;ndar de la funci&#243;n auton&#243;mica estaban anormales<sup>19,20</sup>. Las pruebas de funci&#243;n auton&#243;mica inclu&#237;an (i) medida latido-a-latido de la variaci&#243;n de la frecuencia cardiaca durante ventilaci&#243;n medida, (ii) respuesta postural de la frecuencia cardiaca (raz&#243;n 30:15), (iii) variaci&#243;n de la frecuencia cardiaca durante una maniobra de Valsalva estandarizada y (iv) respuesta hemodin&#225;mica a la postura erecta. A 60 individuos sanos pareados en edad se les utilizaron como grupo control. Ellos no presentaban s&#237;ntomas de ninguna enfermedad, no utilizaban medicamentos y presentaron resultados normales al electrocardiograma de reposo. Los grupos de estudio eran bien balanceados en relaci&#243;n a los datos demogr&#225;ficos y tratamiento farmacol&#243;gico. Todos los individuos fueron informados sobre el protocolo y firmaron el formulario de consentimiento informado para participar del estudio. El Comit&#233; Institucional de &#201;tica aprob&#243; el estudio y est&#225; de acuerdo con los principios postulados en la Declaraci&#243;n de Helsinki de 1983. </p>
      <p>
        <bold>An&#225;lisis de la variabilidad de la frecuencia cardiaca (VFC)</bold>
      </p>
      <p>La prueba de frecuencia cardiaca durante respiraci&#243;n profunda<sup>21-23</sup> se la condujo con el individuo en posici&#243;n supina durante el registro electrocardiogr&#225;fico est&#225;ndar. Se ense&#241;aron a los individuos a respirar a una tasa de 6 ciclos respiratorios por minuto; 5s para cada inhalaci&#243;n y 5s para cada exhalaci&#243;n. Se registr&#243; el ECG de forma continua a 25 mm/segundo por 5 minutos mientras que los pacientes respiraban de acuerdo con las instrucciones recibidas. Las alteraciones latido-a-latido en la frecuencia cardiaca se evaluaron por el m&#233;todo de dominio de tiempo. Se calcul&#243; el intervalo R-R en cada ciclo respiratorio y se tuvo en cuenta un intervalo R-R promedio para el c&#225;lculo de la VFC. La variabilidad de la frecuencia cardiaca se calcul&#243; como la diferencia entre los intervalos R-R m&#225;s corto y m&#225;s largo. La prueba de frecuencia cardiaca durante respiraci&#243;n profunda se eligi&#243; como un test corto a la cabecera del paciente, basado en la experiencia alcanzada en la prueba de control nervioso auton&#243;mico del coraz&#243;n en pacientes con DM. El resultado de la prueba fue preespecificado como normal si hubiera diferencia de 10 latidos o m&#225;s por minuto entre la frecuencia m&#225;s corta y m&#225;s r&#225;pida.</p>
      <p>
        <bold>Respiraci&#243;n diafragm&#225;tica</bold>
      </p>
      <p>Un fisioterapeuta del hospital ense&#241;&#243; la respiraci&#243;n diafragm&#225;tica (respiraci&#243;n abdominal) y controles a los pacientes. Se les solicit&#243; a los individuos que realizaran la respiraci&#243;n diafragm&#225;tica en la posici&#243;n supina. Se les pidi&#243; que inhalaran lenta y profundamente por la nariz hasta el fundo de los pulmones, de modo que enviaran el aire a los pulmones, tan profundamente hacia abajo, lo m&#225;s posible. El t&#243;rax se mueve levemente mientras que el abdomen se expande. El diafragma se mueve hacia abajo. Tras una respiraci&#243;n profunda, se le ped&#237;a al paciente que prendiera la respiraci&#243;n por un momento y tras ello exhalara lentamente por medio de expiraci&#243;n controlada. </p>
      <p>El grupo de intervenci&#243;n de ejercicio respiratorio se dividi&#243; prospectivamente entre aquellos que estaban dispuestos a realizar los ejercicios regularmente (grupo adherente: 80 pacientes y 32 controles) y aquellos que no estaban dispuestos (grupo no-adherente: 65 pacientes y 28 controles). Los pacientes y controles en el grupo adherente fueron incentivados a ejecutar el ejercicio respiratorio diafragm&#225;tico completo 10 veces de cada vez en la posici&#243;n supina con intervalos de 30s a 1 minuto de descanso y entonces, empezar de nuevo. Se les recomendaron a practicar la respiraci&#243;n diafragm&#225;tica por 10 a 15 minutos, dos veces al d&#237;a (por la ma&#241;ana y por la noche), durante un a&#241;o y despu&#233;s volver a la observaci&#243;n. Los pacientes y los controles se siguieron en el ambulatorio por un per&#237;odo de 12 meses, con visitas en intervalos de 30 d&#237;as. Durante la visita, el fisioterapeuta entrevistaba los individuos y registraba los detalles del r&#233;gimen de ejercicios respiratorios. Se les motivaron a continuar con los ejercicios respiratorios de modo regular. En el hospital, un m&#233;dico orient&#243; a los individuos sobre el manejo de la enfermedad isqu&#233;mica cardiaca y DM tipo 2 y el rol de los ejercicios respiratorios en el manejo de las enfermedades. Cada individuo recibi&#243; un cuaderno con instrucciones y beneficios de los ejercicios respiratorios e ilustraciones de la respiraci&#243;n abdominal. Los individuos fueron orientados a tomar nota sobre el tratamiento medicamentoso, dieta y otras actividades f&#237;sicas durante el per&#237;odo del estudio. Durante los 12 meses de seguimiento, un m&#233;dico y un fisioterapeuta hicieron la supervisi&#243;n de todos los individuos incluidos en el estudio. Los resultados de ambos grupos adherente y no-adherente se grabaron para registro del seguimiento. Durante el per&#237;odo de seguimiento de 3 y 12 meses, se registraron la VFC, glucemia de ayuno, peso corporal y niveles de hemoglobina glicosilada. Las actividades f&#237;sicas de los individuos, peso corporal, terapia medicamentosa, dietas, etc., se verificaron y cualesquiera problemas encontrados durante los ejercicios respiratorios se discutieron. </p>
      <p>Todos los resultados fueron expresados como promedio &#177; error est&#225;ndar del promedio o n&#250;meros y porcentajes. Se emple&#243; el paquete estad&#237;stico para ciencias sociales SPSS versi&#243;n 11 para todos los an&#225;lisis estad&#237;sticos. La prueba U de Mann-Whitney se utiliz&#243; para comparar varios par&#225;metros entre diferentes grupos. Se emple&#243; la prueba de rangos con signos (<italic>Wilcoxon Signed Rank Test</italic>) para comparar los resultados entre registros basales y de seguimiento. Para evaluar si la respiraci&#243;n diafragm&#225;tica aislada influenci&#243; la VFC, una prueba de regresi&#243;n m&#250;ltiple <italic>stepwise</italic> se llev&#243; a cabo. Valores de p &lt; 0,05 se consideraron estad&#237;sticamente significantes.</p>
      <p>
        <bold>Resultados</bold>
      </p>
      <p>Las caracter&#237;sticas cl&#237;nicas de los pacientes est&#225;n detalladas en la <xref ref-type="table" rid="tab01-body3">Tabla 1</xref>. Los tres grupos de estudio y el grupo control eran bien equilibrados con relaci&#243;n a los datos demogr&#225;ficos. Los grupos de estudio no difirieron significativamente con relaci&#243;n a la edad, duraci&#243;n de la diabetes y medicaci&#243;n. Hubo una disminuci&#243;n significativa en la VFC en los pacientes con DCI sin diabetes (p&lt;0,01) cuando comparados con los controles sanos. El grupo con DCI y diabetes mellitus (p&lt;0,01) y el grupo con neuropat&#237;a tambi&#233;n ten&#237;an VFC significantemente reducida (p&lt;0,01) cuando comparados a los controles. Los pacientes con DCI sin diabetes presentaban VFC significantemente m&#225;s alta (p&lt;0,05) que aquellos con DCI sin DM y con neuropat&#237;a diab&#233;tica (ND). No hubo diferencia significante con relaci&#243;n a la VFC entre el grupo con DCI y DM y el grupo con DCI y ND. La HbA<sub>1C</sub> y la glucemia de ayuno eran significantemente m&#225;s altas en el grupo con DCI y DM (p&lt;0,01) y en el grupo con DCI y ND (p&lt;0,01), cuando comparados con los grupos control y DCI (<xref ref-type="table" rid="tab02-body3">Tabla 2</xref>).</p>
      <table-wrap id="tab01-body3">
        <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt01-es.jpg"/></table-wrap>
      <table-wrap id="tab02-body3">
        <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt02-es.jpg"/></table-wrap>
      <p>Como se pudo ver en la <xref ref-type="table" rid="tab03-body3">Tabla 3</xref>, los pacientes con DCI sin DM y aquellos con DM con o sin neuropat&#237;a mostraron un aumento significante en la VFC (p&lt;0,01) tras tres meses y un a&#241;o de seguimiento de la respiraci&#243;n diafragm&#225;tica. Un aumento m&#225;s estad&#237;sticamente significante en la VFC se registr&#243; (p&lt;0,01 - para todos los grupos) tras un a&#241;o de seguimiento, en comparaci&#243;n con los registros basales en todos los grupos del estudio. Un aumento en la VFC tras el seguimiento fue significantemente mayor (p&lt;0.01) en el grupo con DCI y DM que en el grupo DCI con ND.</p>
      <table-wrap id="tab03-body3">
        <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt03-es.jpg"/></table-wrap>
      <p>La pr&#225;ctica regular de la respiraci&#243;n diafragm&#225;tica aument&#243; la VFC en los individuos control tambi&#233;n luego de un a&#241;o (p&lt;0,01) (<xref ref-type="table" rid="tab03-body3">Tabla 3</xref>). Una disminuci&#243;n significante en los niveles de HbA<sub>1C</sub> (p&lt;0,01) y glucosa (p&lt;0,01) se observ&#243; tras 3 y 12 meses de seguimiento en el grupo adherente. Aunque los niveles de HbA<sub>1C</sub> y glucosa fueran significantemente m&#225;s altos (p&lt;0,01) que en los controles y en el grupo con DCI, la pr&#225;ctica regular de respiraci&#243;n diafragm&#225;tica significantemente disminuy&#243; esos par&#225;metros metab&#243;licos tras 12 meses de seguimiento, cuando comparados con los niveles basales (<xref ref-type="table" rid="tab04-body3">Tabla 4</xref>). La <xref ref-type="table" rid="tab05-body3">Tabla 5</xref> detalla la VFC registrada en los controles no-adherentes y en los pacientes con DCI tras 3 meses y 12 meses. No hubo diferencia significante en la VFC tras 3 meses de seguimiento en todos los grupos no-adherentes. Hubo una diferencia significante en la VFC en los pacientes con DCI sin DM (p&lt;0,01), DCI con DM (p&lt;0,01) y DCI con ND (p&lt;0,01) tras un a&#241;o de seguimiento del estudio (<xref ref-type="table" rid="tab05-body3">Tabla 5</xref>). No se registr&#243; ninguna diferencia significante en los par&#225;metros metab&#243;licos (HbA<sub>1C</sub> y glucemia) luego del primer per&#237;odo de seguimiento, pero la HbA<sub>1C</sub> aument&#243; significantemente tras un a&#241;o de seguimiento en pacientes con DCI y ND (p&lt;0,01). Los niveles de glucemia aumentaron significantemente en pacientes con DCI no-adherentes sin DM (p&lt;0,05), DCI con DM (p&lt;0,01) y DCI con ND (p&lt;0,01) indicando que la condici&#243;n de la enfermedad empeor&#243; en la ausencia de la respiraci&#243;n diafragm&#225;tica (<xref ref-type="table" rid="tab06-body3">Tabla 6</xref>).</p>
      <table-wrap id="tab04-body3">
        <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt04-es.jpg"/></table-wrap>
      <table-wrap id="tab05-body3">
        <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt05-es.jpg"/></table-wrap>
      <table-wrap id="tab06-body3">
        <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt06-es.jpg"/></table-wrap>
      <p>Cuando se compar&#243; la VFC entre los grupos adherente y no-adherente luego de un a&#241;o de seguimiento, un aumento m&#225;s significante se registr&#243; en todos los grupos, incluyendo los controles (p&lt;0,01) (<xref ref-type="table" rid="tab07-body3">Tabla 7</xref>). En los grupos no-adherentes, hubo una disminuci&#243;n significante en la VFC entre los pacientes con DCI y DM y pacientes con DCI y ND (p&lt;0.01) cuando comparados con los pacientes adherentes.</p>
      <table-wrap id="tab07-body3">
        <graphic xlink:href="1678-4170-abc-92-06-0457-00008-gt07-es.jpg"/></table-wrap>
      <p>El an&#225;lisis de regresi&#243;n m&#250;ltiple indic&#243; que la respiraci&#243;n, aisladamente, fue responsable de un 58,8% (R=0,588) de la variaci&#243;n en la VFC luego de un a&#241;o de seguimiento. Cuando otras variables predictivas se incluyeron, la contribuci&#243;n de la respiraci&#243;n aument&#243; para el 72% (R=0,725). La respiraci&#243;n diafragm&#225;tica, aisladamente, mostr&#243; un aporte para los cambios observados en la VFC. El coeficiente de la respiraci&#243;n diafragm&#225;tica fue el mayor, mostrando el m&#225;ximo de aporte en comparaci&#243;n a otros predictores, tales como medicaci&#243;n, duraci&#243;n de la diabetes, edad, etc.</p>
      <p>
        <bold>Discusi&#243;n</bold>
      </p>
      <p>El presente estudio revel&#243; que hubo una disminuci&#243;n significante en la VFC en pacientes con enfermedad cardiaca isqu&#233;mica y pacientes con enfermedad cardiaca isqu&#233;mica y diabetes mellitus. Pocos estudios relataron la reducci&#243;n de la VFC en pacientes con diabetes. En pacientes diab&#233;ticos sin evidencia de neuropat&#237;a auton&#243;mica, la reducci&#243;n en la VFC durante condiciones controladas tambi&#233;n ha sido relatada<sup>11,24,25</sup>. La VFC anormal en pacientes diab&#233;ticos representa un aumento de riesgo para arritmias ventriculares, as&#237; como morbilidad y mortalidad cardiovascular total<sup>12</sup>. La disminuci&#243;n en la VFC en pacientes con DCI y diabetes refleja las reducciones en las modulaciones simp&#225;tica y parasimp&#225;tica del coraz&#243;n. La disminuci&#243;n observada en la VFC en pacientes con DCI podr&#237;a ser debida a la disfunci&#243;n auton&#243;mica como un resultado de la isquemia. Una regulaci&#243;n desbalanceada del sistema nervoso auton&#243;mico cardiaco es una de las alteraciones patofisiol&#243;gicas importantes en la DCI<sup>26,27</sup>. Hubo una disminuci&#243;n m&#225;s significante en la VFC de pacientes con DCI y neuropat&#237;a que en pacientes sin neuropat&#237;a. La VFC puede estar disminuida en pacientes con diabetes debido a la neuropat&#237;a auton&#243;mica cardiovascular. Se ha observado que en pacientes adultos con diabetes, hay una disfunci&#243;n del sistema nervioso auton&#243;mico con la larga duraci&#243;n de la enfermedad<sup>26-29</sup>. La neuropat&#237;a auton&#243;mica diab&#233;tica es seguida inicialmente por disturbios del sistema parasimp&#225;tico y, posteriormente, del sistema simp&#225;tico<sup>28</sup>. Nuestra evaluaci&#243;n de las alteraciones en la VFC apoya la idea de que hay una disminuci&#243;n en la funci&#243;n auton&#243;mica en el inicio del desarrollo de la diabetes y que la diabetes conlleva un descenso progresivo en la funci&#243;n auton&#243;mica y que la VFC puede ser un m&#233;todo eficiente de detecci&#243;n precoz de la neuropat&#237;a auton&#243;mica diab&#233;tica. </p>
      <p>En el presente estudio, la pr&#225;ctica de la respiraci&#243;n abdominal mejor&#243; las mediciones de la VFC. El presente estudio evidenci&#243; que la variaci&#243;n de la frecuencia cardiaca mejor&#243; en pacientes con DCI sin diabetes y en pacientes con DCI y diabetes que practicaron regularmente ejercicios de respiraci&#243;n. Hubo un aumento significante en la VFC en controles normales que practicaron la respiraci&#243;n diafragm&#225;tica por un a&#241;o. La mejora observada en la VFC con la t&#233;cnica modificada de respiraci&#243;n puede ser debida al efecto directo de la respiraci&#243;n sobre el sistema nervioso auton&#243;mico controlando el coraz&#243;n<sup>30</sup>. En el cuerpo humano, la mayor&#237;a de los par&#225;metros de funci&#243;n cardiaca parece estar relacionada al modo respiraci&#243;n. La respiraci&#243;n adecuada puede influenciar hasta aun par&#225;metros cardiacos sutiles, como la fracci&#243;n de eyecci&#243;n, presi&#243;n a&#243;rtica y presi&#243;n arterial pulmonar, pre y post-carga, y hasta aun la oxigenaci&#243;n de los tejidos<sup>31,32</sup>. La respiraci&#243;n diafragm&#225;tica puede reducir la actividad simp&#225;tica al aumentar el ritmo inhibitorio central<sup>33</sup>. Debido al aumento del volumen tidal durante la respiraci&#243;n diafragm&#225;tica profunda, hay una activaci&#243;n del reflejo de Hering-Breuer<sup>34</sup>, lo que reduce la sensibilidad quimiorrefleja y puede aumentar el barorreflejo y reducir la actividad simp&#225;tica<sup>34-36</sup>. Parece que la respiraci&#243;n profunda induce a una disminuci&#243;n generalizada en las v&#237;as excitatorias que regulan el sistema respiratorio y cardiovascular. Los sistemas respiratorio y cardiovascular comparten mecanismos de control similares y una alteraci&#243;n en uno de los sistemas modificar&#225; el funcionamiento del otro<sup>15,35</sup>. En la enfermedad cardiaca isqu&#233;mica, hay un aumento en la activaci&#243;n simp&#225;tica y quimiorrefleja y la respiraci&#243;n diafragm&#225;tica indujo a una disminuci&#243;n en la activaci&#243;n simp&#225;tica, lo que puede haber aumentado la VFC. Hubo una mejora importante en los par&#225;metros metab&#243;licos estudiados tras la pr&#225;ctica regular de respiraci&#243;n diafragm&#225;tica en el presente estudio. La disminuci&#243;n en la HbA<sub>1C</sub> est&#225; de acuerdo con los estudios previos<sup>37,38</sup>. La disminuci&#243;n en la hemoglobina glicosilada y la glucosa sangu&#237;nea registrada en pacientes con DCI y diabetes y en pacientes con DCI y neuropat&#237;a diab&#233;tica indica que los ejercicios regulares con respiraci&#243;n prolongada puede significantemente mejorar la homeostasis de la glucosa y el tan necesario control gluc&#233;mico en esos pacientes. La hiperglicemia y sus consecuencias metab&#243;licas relacionadas conllevan la patog&#233;nesis de la neuropat&#237;a auton&#243;mica en la diabetes mellitus<sup>11,24</sup>. La mejora observada en los par&#225;metros metab&#243;licos se podr&#237;a atribuir a los cambios auton&#243;micos causados por la respiraci&#243;n diafragm&#225;tica, la cual disminuy&#243; la actividad simp&#225;tica<sup>15,35,39,40</sup>. </p>
      <p>El estr&#233;s puede tener efectos negativos en la salud y el hecho de que pacientes con DM tipo 2 puedan presentar riesgo aumentado de experimentar estr&#233;s est&#225; asociado a la liberaci&#243;n de hormonas contraregulatorias que resultar&#225;n en la elevaci&#243;n de los niveles de glucem&#237;a<sup>41</sup>. Adem&#225;s de ello, el estr&#233;s puede interferir con el control de la diabetes indirectamente, por medio de efectos en la dieta, ejercicio y otros comportamientos de autocuidado. Se puede gestionar el estr&#233;s por medio del empleo de programas comportamentales de gesti&#243;n de estr&#233;s o con medicamentos. Ambos tipos de intervenci&#243;n se han mostrado eficaces en la mejora del control gluc&#233;mico en pacientes con diabetes mellitus tipo 2<sup>38,42,43</sup>. El entrenamiento de la gesti&#243;n de estr&#233;s incluye t&#237;picamente relajaci&#243;n muscular progresiva con o sin bioretroalimentaci&#243;n de electromiograf&#237;a, im&#225;genes mentales, respiraci&#243;n diafragm&#225;tica, yoga e instrucciones sobre como modificar las respuestas fisiol&#243;gicas, cognitivas y comportamentales al estr&#233;s. Relatos de investigadores al estudiar el efecto de la gesti&#243;n de estr&#233;s sobre el control gluc&#233;mico han sido inconsistentes<sup>44,45</sup>, sin embargo, diversos de esos estudios ten&#237;an un bajo poder y otros ten&#237;an problemas de proyecto. Nuestro estudio apoya la idea de que la intervenci&#243;n en forma de pr&#225;ctica de respiraci&#243;n diafragm&#225;tica profunda conllevar&#237;a una mejora en el control gluc&#233;mico y tambi&#233;n reducir&#237;a la insuficiencia auton&#243;mica cardiaca en pacientes con DCI y diabetes mellitus.</p>
      <p>La actividad f&#237;sica, como una intervenci&#243;n no-farmacol&#243;gica, es muy importante en pacientes con s&#237;ndromes metab&#243;licos en quien la ocurrencia simult&#225;nea de diabetes est&#225; seguida de un aumento en la actividad del sistema nervioso simp&#225;tico. As&#237;, el efecto de la respiraci&#243;n diafragm&#225;tica en la VFC se debe principalmente a la alteraci&#243;n en el equilibrio entre la actividad del sistema nervioso simp&#225;tico y parasimp&#225;tico sobre el coraz&#243;n. La pr&#225;ctica de largo plazo de la respiraci&#243;n diafragm&#225;tica conlleva cambios estables en el control auton&#243;mico del coraz&#243;n y resulta en el aumento de la VFC. Se sabe que la respiraci&#243;n abdominal trae calma interior, relajaci&#243;n y calentamiento perif&#233;rico. Se considera la respiraci&#243;n diafragm&#225;tica como la forma m&#225;s sana de respiraci&#243;n, adem&#225;s de ser ella una de las formas m&#225;s sencillas, aunque la m&#225;s efectiva, de las t&#233;cnicas de gesti&#243;n de estr&#233;s<sup>16,32</sup>. La respiraci&#243;n diafragm&#225;tica intenta revertir el equilibrio auton&#243;mico en favor del est&#237;mulo parasimp&#225;tico desde el est&#237;mulo simp&#225;tico en pacientes diab&#233;ticos, reduciendo la sintomatolog&#237;a funcional y promoviendo un impacto positivo en la salud de los indiv&#237;duos<sup>40</sup>. El estudio claramente indica una mejora en el grupo de intervenci&#243;n. Eso prueba que la respiraci&#243;n abdominal es mucho m&#225;s ben&#233;fica a los pacientes con DCI, DCI con diabetes y DCI con neuropat&#237;a auton&#243;mica diab&#233;tica. </p>
      <p>
        <bold>Limitaciones del estudio</bold>
      </p>
      <p>Hay varias limitaciones en el estudio. La ausencia de datos metab&#243;licos, la falta de medidas cardiovasculares adicionales, el efecto de diferentes composiciones de alimentos sobre la VFC, la medida de la capacidad de ejercicio (VO<sub>2</sub> pico) y la ausencia de datos ecocardiogr&#225;ficos son las mayores limitaciones. Una de las dificultades enfrentadas por nuestro grupo de investigaci&#243;n es la falta de an&#225;lisis de la VFC en el dominio de frecuencia. Nuestro laboratorio no estaba espec&#237;ficamente equipado para ese prop&#243;sito, por tanto, no pudimos conducir el an&#225;lisis de VFC por an&#225;lisis espectral, que tiene mayor sensibilidad y especificidad. Sin embargo, la utilidad cl&#237;nica de los hallazgos de la VFC desde los registros del electrocardiograma de corta duraci&#243;n es bien establecida<sup>46,47</sup>. La influencia del entrenamiento medicamentoso y su discontinuidad sobre la VFC se deber&#237;an tener en cuenta cuidadosamente. Por razones &#233;ticas, no descontinuamos el tratamiento por un per&#237;odo de tiempo extenso. </p>
      <p>En conclusi&#243;n, el estudio confirma que la VFC se reduce en pacientes con DCI que tienen diabetes y que esa disminuci&#243;n de la VFC es mayor en pacientes con neuropat&#237;a diab&#233;tica, indicando un severo desequilibrio auton&#243;mico. La pr&#225;ctica regular de respiraci&#243;n diafragm&#225;tica aumenta la VFC en controles normales y en pacientes con DCI y DM. Los datos observados deber&#237;an incentivar la pr&#225;ctica regular de respiraci&#243;n diafragm&#225;tica como terapia no-farmacol&#243;gica en pacientes con enfermedad cardiaca isqu&#233;mica con o sin diabetes y neuropat&#237;a diab&#233;tica, junto con el tratamiento usual. El objetivo del abordaje ser&#237;a mantener un excelente equilibrio del sistema nervioso auton&#243;mico y regulaci&#243;n fisiol&#243;gica de la frecuencia cardiaca. Ya que la respiraci&#243;n diafragm&#225;tica es una actividad f&#237;sica f&#225;cil, segura y psicol&#243;gicamente aceptable, consideramos este un hallazgo valioso y como los perfiles sociodemogr&#225;ficos de los pacientes en el presente estudio se asemejaron a los de otros estudios internacionales, consideramos que el resultado del presente estudio se puede aplicar a otras poblaciones. Estudios futuros pueden ser necesarios para establecer los beneficios, a largo-plazo, de la respiraci&#243;n diafragm&#225;tica sobre otros m&#233;todos establecidos de medici&#243;n de la VFC en muestras mayores.</p>
      <p>
        <bold>Potencial Conflicto de Intereses</bold>
      </p>
      <p>Declaro no haber conflicto de intereses pertinentes.</p>
      <p>
        <bold>Fuentes de Financiamiento</bold>
      </p>
      <p>El presente estudio no tuvo fuentes de financiamiento externas.</p>
      <p>
        <bold>V&#237;nculo Acad&#233;mico</bold>
      </p>
      <p>No hay v&#237;nculo de este estudio a programas de post grado.</p>
      <p>
        <bold>Referencias</bold>
      </p>
    </body>
  </sub-article>
</article>
