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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq. Bras. Cardiol.</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</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">bG7DvmxyqCgBHCCKgwL5qnB</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2014000100007</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2013005000109</article-id>
      <article-id pub-id-type="other">0007</article-id>
      <article-id pub-id-type="publisher-id">S0066-782X2013005000109</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20130230</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="pt">Exerc&#237;cio Aer&#243;bio Intervalado Induz Maior Redu&#231;&#227;o na
               Sobrecarga Card&#237;aca na Recupera&#231;&#227;o em Ratos</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Borges</surname>
            <given-names>Juliana Pereira</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="corresp" rid="c01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Masson</surname>
            <given-names>Gustavo Santos</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Tibiri&#231;&#225;</surname>
            <given-names>Eduardo</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lessa</surname>
            <given-names>Marcos Adriano</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <aff id="aff01">
          <institution content-type="orgname">Instituto Oswaldo Cruz</institution>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country>Brasil</country>
          <institution content-type="original">Instituto Oswaldo Cruz - FIOCRUZ, Rio de
                  Janeiro, RJ - Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c01"><bold>Correspond&#234;ncia: Juliana Pereira Borges</bold>, Av. Brasil 4365, Manguinhos,
               CEP 21040-900, Rio de Janeiro, RJ - Brasil. E-mail:
                  <email>julipborges@gmail.com</email></corresp>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial Conflito de Interesses</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="collection">
        <month>1</month>
        <year>2014</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>26</day>
        <month>11</month>
        <year>2013</year>
      </pub-date>
      <volume>102</volume>
      <issue>1</issue>
      <fpage>47</fpage>
      <lpage>53</lpage>
      <history>
        <date date-type="received">
          <day>19</day>
          <month>06</month>
          <year>2013</year>
        </date>
        <date date-type="rev-recd">
          <day>13</day>
          <month>08</month>
          <year>2013</year>
        </date>
        <date date-type="accepted">
          <day>16</day>
          <month>08</month>
          <year>2013</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">
          <license-p>This is an Open Access article distributed under the terms of the Creative
                  Commons Attribution Non-Commercial License which permits unrestricted
                  non-commercial use, distribution, and reproduction in any medium, provided the
                  original work is properly cited. </license-p>
        </license>
      </permissions>
      <abstract xml:lang="pt">
        <sec>
          <title>Fundamento:</title>
          <p> O treinamento aer&#243;bio intervalado produz maior benef&#237;cio na fun&#231;&#227;o cardiovascular
                  comparado ao treinamento aer&#243;bio cont&#237;nuo. </p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p> O presente estudo teve como objetivo analisar os efeitos de ambas as modalidades
                  nas respostas hemodin&#226;micas de ratos sadios. </p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p> Ratos machos foram distribu&#237;dos aleatoriamente em tr&#234;s grupos: exerc&#237;cio cont&#237;nuo
                  (EC, n = 10); exerc&#237;cio intervalado (EI, n = 10); e controle (C, n = 10). A sess&#227;o
                  do grupo EC consistiu em 30 min &#224; intensidade de 50% da velocidade m&#225;xima (Vel
                  M&#225;x). O grupo EI realizou 30 min, incluindo tr&#234;s per&#237;odos de 4 min a 60% da Vel
                  M&#225;x intercalados com 4 min de recupera&#231;&#227;o a 40% da Vel M&#225;x. Frequ&#234;ncia Card&#237;aca
                  (FC), Press&#227;o Arterial (PA) e Duplo Produto (DP) foram medidos antes, durante e
                  ap&#243;s o exerc&#237;cio. </p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p> Os grupos EC e EI apresentaram aumento da PA sist&#243;lica e DP durante o exerc&#237;cio
                  em compara&#231;&#227;o ao repouso. Ap&#243;s o t&#233;rmino do exerc&#237;cio, o grupo EC mostrou menor
                  resposta da PA sist&#243;lica e do DP em rela&#231;&#227;o ao repouso, enquanto o grupo EI
                  apresentou menor PA sist&#243;lica e PA m&#233;dia. No entanto, somente no grupo EI a FC e o
                  DP apresentaram menor resposta na recupera&#231;&#227;o. </p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p> Uma sess&#227;o de exerc&#237;cio intervalado em ratos sadios induziu respostas
                  hemodin&#226;micas similares durante o exerc&#237;cio &#224;s obtidas em exerc&#237;cio cont&#237;nuo. Na
                  recupera&#231;&#227;o, o exerc&#237;cio intervalado promoveu maiores redu&#231;&#245;es no esfor&#231;o card&#237;aco
                  do que em sess&#245;es cont&#237;nuas de exerc&#237;cio.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <kwd>Press&#227;o arterial</kwd>
        <kwd>Respostas agudas ao exerc&#237;cio</kwd>
        <kwd>Exerc&#237;cio intermitente</kwd>
      </kwd-group>
      <funding-group>
        <award-group>
          <funding-source>CNPq</funding-source>
        </award-group>
        <award-group>
          <funding-source>FAPERJ</funding-source>
        </award-group>
        <award-group>
          <funding-source>FIOCRUZ</funding-source>
        </award-group>
      </funding-group>
      <counts>
        <fig-count count="2"/>
        <table-count count="1"/>
        <equation-count count="0"/>
        <ref-count count="24"/>
        <page-count count="7"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>O treinamento aer&#243;bio intervalado ou intermitente, originalmente usado em treinamento
            desportivo, consiste de est&#237;mulos alternados de alta e baixa intensidade de
               exerc&#237;cio<xref ref-type="bibr" rid="B01">1</xref><sup>-</sup><xref ref-type="bibr" rid="B04">4</xref>. H&#225; um ac&#250;mulo de evid&#234;ncias sugerindo que a magnitude dos
            benef&#237;cios advindos do exerc&#237;cio f&#237;sico aumenta proporcionalmente de acordo com a
            intensidade de cada sess&#227;o de exerc&#237;cio que constitui o programa de treinamento<xref ref-type="bibr" rid="B05">5</xref>. Os efeitos observados na fun&#231;&#227;o
            cardiorrespirat&#243;ria e muscular levaram pesquisadores a considerar a aplica&#231;&#227;o do
            exerc&#237;cio intervalado no campo das doen&#231;as cardiovasculares<xref ref-type="bibr" rid="B01">1</xref>. Gibala e cols.<xref ref-type="bibr" rid="B06">6</xref> mostraram
            que esse treinamento &#233; mais eficiente em induzir r&#225;pidas adapta&#231;&#245;es musculares e na
               <italic>performance</italic> comparado ao treinamento cont&#237;nuo. Em um volume
            marcadamente menor de treinamento, o exerc&#237;cio intervalado promove benef&#237;cios similares
            na capacidade de exerc&#237;cio e express&#227;o de enzimas antioxidantes, aos observados em
            treinamento tradicionais conservativos de exerc&#237;cio cont&#237;nuo<xref ref-type="bibr" rid="B06">6</xref>. Molmen-Hansen e cols.<xref ref-type="bibr" rid="B07">7</xref>
            recentemente demonstraram que sess&#245;es de exerc&#237;cio intermitente eram capazes de reduzir
            a Press&#227;o Arterial (PA) e melhorar a fun&#231;&#227;o mioc&#225;rdica em paciente hipertensos. Al&#233;m
            disso, v&#225;rios estudos pr&#233;vios indicam que o treinamento intervalado em intensidade
            relativamente mais alta pode ser usado tanto na pr&#225;tica cl&#237;nica quanto
            experimentalmente, e que essa metodologia induz maiores efeitos ben&#233;ficos ao
               cora&#231;&#227;o<xref ref-type="bibr" rid="B08">8</xref><sup>,</sup><xref ref-type="bibr" rid="B09">9</xref>. Essas caracter&#237;sticas sugerem que o treinamento intermitente pode
            ser mais apropriado a indiv&#237;duos com s&#237;ndrome metab&#243;lica, dislipidemia e outros fatores
            de risco cardiovascular<xref ref-type="bibr" rid="B10">10</xref><sup>-</sup><xref ref-type="bibr" rid="B12">12</xref>. No entanto, pouco se sabe sobre as diferen&#231;as
            agudas e subagudas obtidas nessa metodologia de exerc&#237;cio em rela&#231;&#227;o ao treinamento
            cont&#237;nuo tradicional. O efeito agudo se refere &#224; resposta fisiol&#243;gica observada enquanto
            o exerc&#237;cio &#233; realizado (tais como o aumento na Frequ&#234;ncia Card&#237;aca (FC) e PA
            sist&#243;lica). J&#225; os efeitos subagudos ocorrem imediatamente ap&#243;s o t&#233;rmino do exerc&#237;cio, e
            envolvem os mecanismos pelos quais ocorre a transfer&#234;ncia dos sinais agudos em
            adapta&#231;&#245;es desenvolvidas ao longo do per&#237;odo de treinamento<xref ref-type="bibr" rid="B13">13</xref>. Dessa forma, torna-se fundamental estudar tais efeitos nas
            metodologias intervalada e cont&#237;nua. Considerando que o exerc&#237;cio cont&#237;nuo e intervalado
            poderia promover respostas hemodin&#226;micas de diferente cin&#233;tica e magnitude,
            especialmente importantes quando se trata de comprometimento cardiovascular. O presente
            estudo teve por fim investigar as respostas hemodin&#226;micas agudas e subagudas de ambas as
            metodologias de exerc&#237;cio em ratos.</p>
    </sec>
    <sec sec-type="methods">
      <title>M&#233;todos</title>
      <sec>
        <title>Animais</title>
        <p>Todos os procedimentos realizados foram aprovados pelo Comit&#234; de &#201;tica em Pesquisa da
               Funda&#231;&#227;o Oswaldo Cruz (Protocolo n&#250;mero 31/10-3 LW21-10), consoante &#224; Declara&#231;&#227;o de
               Helsinki. N&#227;o houve conflito de interesse relacionado a este estudo. Durante o
               per&#237;odo experimental, os animais permaneceram em ciclo de luz (12:12 h ciclo
               claro-escuro) e temperatura controlados (22 &#177; 1&#186;C), sendo mantido de tr&#234;s a quatro
               animais por caixa. Foi permitido acesso <italic>ad libitum</italic> aos animais a
               ra&#231;&#227;o padr&#227;o e &#225;gua.</p>
        <p>Ratos wistar machos, pesando entre 300 e 350 g, com idade m&#237;nima de 180 dias, foram
               distribu&#237;dos aleatoriamente em tr&#234;s grupos: exerc&#237;cio cont&#237;nuo (EC, n = 10),
               exerc&#237;cio intervalado (EI, n = 10) e controle (C, n = 10).</p>
      </sec>
      <sec>
        <title>Protocolo de exerc&#237;cio</title>
        <p>O protocolo total consistiu em seis dias consecutivos. Todos os animais foram
               adaptados a esteira de exerc&#237;cios (Modelo HT 2.0, Hectron Fitness Equipment, Rio de
               Janeiro, RJ) ao longo de tr&#234;s dias consecutivos (10 min a 10 m/min). No quarto dia,
               foi realizado teste m&#225;ximo de exerc&#237;cio para determinar velocidade m&#225;xima (Vel M&#225;x)
               obtida. O teste consistiu em velocidade inicial de 5 m/min com incremento de
               velocidade de 1,5 m/min a cada 2 min at&#233; a exaust&#227;o do animal, quando o mesmo
               permanecia na grade de choque apesar do est&#237;mulo sonoro. No quinto dia, os ratos
               foram submetidos ao procedimento cir&#250;rgico de canula&#231;&#227;o descrito na sess&#227;o seguinte.
               E finalmente, no sexto dia, os animais realizaram a sess&#227;o de exerc&#237;cio ou controle.
               Ambos os grupos EI e EC realizaram 30 min de exerc&#237;cio, incluindo 3 min de
               aquecimento e 3 min de desacelera&#231;&#227;o a 30% da Vel M&#225;x. A sess&#227;o do grupo EC consistiu
               em corrida cont&#237;nua a 50% da velocidade m&#225;xima (Vel M&#225;x) obtida em teste m&#225;ximo
               pr&#233;vio. Enquanto o grupo EI realizou tr&#234;s per&#237;odos sucessivos de 4 min a 60% da Vel
               M&#225;x, intercalados com 4 min de recupera&#231;&#227;o a 40% da Vel M&#225;x. Essas intensidades foram
               utilizadas para equalizar o volume da sess&#227;o de exerc&#237;cio entre os grupos e permitir
               a compara&#231;&#227;o entre eles. Pois ao manter a intensidade m&#233;dia em 50% da Vel M&#225;x nos
               dois grupos, a &#250;nica diferen&#231;a se daria pela forma de aplica&#231;&#227;o da intensidade, ou
               seja, intervalado ou n&#227;o. Dessa forma, poss&#237;veis diferen&#231;as encontradas entre os dois
               grupos n&#227;o poderiam ser atribu&#237;das a diferentes cargas de exerc&#237;cio.</p>
      </sec>
      <sec>
        <title>Procedimento cir&#250;rgico e medidas hemodin&#226;micas</title>
        <p>Todos os animais foram anestesiados com pentobarbital (50 mg/kg ip) para implanta&#231;&#227;o
               de c&#226;nula de polietileno (PE-50 preenchido com solu&#231;&#227;o heparinizada de salina) na
               art&#233;ria car&#243;tida esquerda, a fim de obter a medida direta da PA e FC. A c&#226;nula era
               ent&#227;o exteriorizada nas costas do animal, para permitir an&#225;lise 24 h ap&#243;s a
               implanta&#231;&#227;o do cateter, durante a sess&#227;o de exerc&#237;cio ou controle. Portanto, a
               an&#225;lise era feita quando eles estavam conscientes e podiam se movimentar livremente
               durante o experimento.</p>
        <p>Para medi&#231;&#227;o da PA e FC, a c&#226;nula era conectada a um transdutor de press&#227;o (Modelo
               TSD104A, BIOPAC Systems, Inc, Goleta, CA) e a um amplificador de sinal (Modelo
               DA100C, BIOPAC Systems, Inc, Goleta, CA). As medidas eram adquiridas a uma taxa
               amostral de 200 amostras/seg atrav&#233;s de um sistema (Modelo MP150 system, BIOPAC
               Systems, Inc, Goleta, CA) e gravadas usando um <italic>software</italic> espec&#237;fico
               (AcqKnowledge 3.7.3 for Windows, BIOPAC Systems, Inc, Goleta, CA). Os sinais eram
               gravados no repouso (10 min), durante o exerc&#237;cio (a cada 8 min excluindo aquecimento
               e desacelera&#231;&#227;o) e at&#233; 90 min ap&#243;s o t&#233;rmino do exerc&#237;cio (1 min a cada 5 min). Os
               sinais eram analisados batimento a batimento para quantificar mudan&#231;as na PA e FC. O
               Duplo Produto (DP), considerado uma estimativa da carga de trabalho do mioc&#225;rdio, foi
               calculado multiplicando a FC pelo PA sist&#243;lica. </p>
      </sec>
      <sec>
        <title>An&#225;lise estat&#237;stica</title>
        <p>Diferen&#231;as entre os grupos foram analisadas usando ANOVA de duas entradas para
               medidas repetidas, seguida de p&#243;s-teste de Bonferroni. Foi fixado o n&#237;vel de
               signific&#226;ncia em 5%. Todos os resultados foram expressos como m&#233;dia &#177; desvio padr&#227;o.
               As an&#225;lises estat&#237;sticas foram feitas atrav&#233;s do <italic>software</italic> GraphPad
               Prism (Vers&#227;o 5 for Windows, GraphPad Software, Inc, La Jolla, CA).</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Resultados</title>
      <p>Os grupos n&#227;o apresentaram diferen&#231;a estat&#237;stica em rela&#231;&#227;o ao peso corporal (EC: 377,5
            &#177; 16; EI: 374,4 &#177; 18; C: 378,3 &#177; 15 g), e medidas hemodin&#226;micas no repouso. Quanto ao
            teste m&#225;ximo, n&#227;o houve diferen&#231;as estat&#237;sticas entre os grupos para a Vel M&#225;x (EC: 20,5
            &#177; 3; EI: 19,6 &#177; 2; C: 19,2 &#177; 1 m/min), assim como para a dura&#231;&#227;o (EC: 1319,9 &#177; 200; EI:
            1204,5 &#177; 179; C: 1209,4 &#177; 105 seg).</p>
      <p>Os resultados de efeito agudo e subagudo na PA, FC e DP nas diferentes metodologias de
            exerc&#237;cio, est&#227;o demonstrados nas <xref ref-type="fig" rid="f01">figuras 1</xref> e
               <xref ref-type="fig" rid="f02">2</xref>, respectivamente.</p>
      <fig id="f01" fig-type="other">
        <label>Figura 1</label>
        <caption>
          <title>Press&#227;o arterial sist&#243;lica, m&#233;dia e diast&#243;lica durante e ap&#243;s exerc&#237;cio. *p
                  &lt; 0,05 vs. repouso no grupo cont&#237;nuo; #p &lt; 0,05 vs. repouso no grupo
                  intervalado.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-102-01-0047-30230-gf01.jpg"/></fig>
      <fig id="f02" fig-type="other">
        <label>Figura 2</label>
        <caption>
          <title>Frequ&#234;ncia card&#237;aca e duplo produto durante e ap&#243;s exerc&#237;cio. *p &lt; 0,05 vs.
                  repouso no grupo cont&#237;nuo; #p &lt; 0,05 vs. repouso no grupo intervalado.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-102-01-0047-30230-gf02.jpg"/></fig>
      <p>Em rela&#231;&#227;o ao efeito agudo do exerc&#237;cio, o grupo EC apresentou resposta estatisticamente
            maior ap&#243;s 8, 16 e 24 min de exerc&#237;cio para a PA sist&#243;lica, FC e DP quando comparado aos
            valores basais, como observado na <xref ref-type="table" rid="t01">tabela 1</xref>. Al&#233;m
            disso, o grupo EC mostrou PA diast&#243;lica estatisticamente menor ap&#243;s 8, 16 e 24 min de
            exerc&#237;cio em rela&#231;&#227;o ao repouso (<xref ref-type="table" rid="t01">Tabela 1</xref>). J&#225;
            no grupo EI, tamb&#233;m foi encontrada resposta estatisticamente aumentada ap&#243;s 8, 16 e 24
            min de exerc&#237;cio para a PA sist&#243;lica e DP quando comparado ao repouso, enquanto a PA
            diast&#243;lica estava estatisticamente reduzida somente ap&#243;s 8 min de exerc&#237;cio (<xref ref-type="table" rid="t01">Tabela. 1</xref>).</p>
      <table-wrap id="t01">
        <label>Tabela 1</label>
        <caption>
          <title>Respostas hemodin&#226;micas obtidas no basal e durante o exerc&#237;cio f&#237;sico (8, 16 e
                  24 min) para os grupos cont&#237;nuo, intervalado e controle</title>
        </caption>
        <table frame="hsides" rules="rows">
          <tbody>
            <tr>
              <td rowspan="4" align="center">
                <bold>Basal</bold>
              </td>
              <td align="center"> </td>
              <td align="center">
                <bold>PAS</bold>
              </td>
              <td align="center">
                <bold>PAM</bold>
              </td>
              <td align="center">
                <bold>PAD</bold>
              </td>
              <td align="center">
                <bold>FC</bold>
              </td>
              <td align="center">
                <bold>DP</bold>
              </td>
            </tr>
            <tr>
              <td align="center">EC (n = 10)</td>
              <td align="center">132,4 &#177; 11,3</td>
              <td align="center">106,4 &#177; 7,2</td>
              <td align="center">86,2 &#177; 12,3</td>
              <td align="center">378,6 &#177; 28,3</td>
              <td align="center">51136,8 &#177; 5306,3</td>
            </tr>
            <tr>
              <td align="center">EI (n = 10)</td>
              <td align="center">133,5 &#177; 10,8</td>
              <td align="center">109,4 &#177; 7,3</td>
              <td align="center">84,7 &#177; 8,2</td>
              <td align="center">405,6 &#177; 44,7</td>
              <td align="center">54444,0 &#177; 9282,6</td>
            </tr>
            <tr>
              <td align="center">C (n = 10)</td>
              <td align="center">136,7 &#177; 15,9</td>
              <td align="center">110,9 &#177; 12,0</td>
              <td align="center">85,6 &#177; 10,8</td>
              <td align="center">387,4 &#177; 50,4</td>
              <td align="center">53161,5 &#177; 10232,5</td>
            </tr>
            <tr>
              <td rowspan="4" align="center">
                <bold>8 min</bold>
              </td>
              <td align="center"> </td>
              <td align="center">
                <bold>PAS</bold>
              </td>
              <td align="center">
                <bold>PAM</bold>
              </td>
              <td align="center">
                <bold>PAD</bold>
              </td>
              <td align="center">
                <bold>FC</bold>
              </td>
              <td align="center">
                <bold>DP</bold>
              </td>
            </tr>
            <tr>
              <td align="center">EC (n = 10)</td>
              <td align="center">152,2<xref ref-type="table-fn" rid="t01-fn02">#</xref>
                        &#177; 11,4</td>
              <td align="center">109,7 &#177; 7,6</td>
              <td align="center">70,4<xref ref-type="table-fn" rid="t01-fn01">*</xref>
                        &#177; 12,6</td>
              <td align="center">438,5<xref ref-type="table-fn" rid="t01-fn02">#</xref>
                        &#177; 34,7</td>
              <td align="center">66593,9<xref ref-type="table-fn" rid="t01-fn02">#</xref>
                        &#177; 6773,5</td>
            </tr>
            <tr>
              <td align="center">EI (n = 10)</td>
              <td align="center">156,5<xref ref-type="table-fn" rid="t01-fn02">#</xref>
                        &#177; 15,8</td>
              <td align="center">112,4 &#177; 11,1</td>
              <td align="center">74,6<xref ref-type="table-fn" rid="t01-fn01">*</xref>
                        &#177; 11,5</td>
              <td align="center">442,5 &#177; 61,2</td>
              <td align="center">70002,4<xref ref-type="table-fn" rid="t01-fn01">*</xref>
                        &#177; 15835,7</td>
            </tr>
            <tr>
              <td align="center">C (n = 10)</td>
              <td align="center">NA</td>
              <td align="center">NA</td>
              <td align="center">NA</td>
              <td align="center">NA</td>
              <td align="center">NA</td>
            </tr>
            <tr>
              <td rowspan="4" align="center">
                <bold>16 min</bold>
              </td>
              <td align="center"> </td>
              <td align="center">
                <bold>PAS</bold>
              </td>
              <td align="center">
                <bold>PAM</bold>
              </td>
              <td align="center">
                <bold>PAD</bold>
              </td>
              <td align="center">
                <bold>FC</bold>
              </td>
              <td align="center">
                <bold>DP</bold>
              </td>
            </tr>
            <tr>
              <td align="center">EC (n = 10)</td>
              <td align="center">154,8<xref ref-type="table-fn" rid="t01-fn02">#</xref>
                        &#177; 17,0</td>
              <td align="center">110,7 &#177; 8,0</td>
              <td align="center">72,1<xref ref-type="table-fn" rid="t01-fn01">*</xref>
                        &#177; 13,8</td>
              <td align="center">446,9<xref ref-type="table-fn" rid="t01-fn02">#</xref>
                        &#177; 33,8</td>
              <td align="center">68607,2<xref ref-type="table-fn" rid="t01-fn02">#</xref>
                        &#177; 7001,4</td>
            </tr>
            <tr>
              <td align="center">EI (n = 10)</td>
              <td align="center">153,4<xref ref-type="table-fn" rid="t01-fn02">#</xref>
                        &#177; 15,8</td>
              <td align="center">112,8 &#177; 10,4</td>
              <td align="center">76,9 &#177; 11,5</td>
              <td align="center">441,4 &#177; 49,2</td>
              <td align="center">68342,1<xref ref-type="table-fn" rid="t01-fn01">*</xref>
                        &#177; 13838,3</td>
            </tr>
            <tr>
              <td align="center">C (n = 10)</td>
              <td align="center">NA</td>
              <td align="center">NA</td>
              <td align="center">NA</td>
              <td align="center">NA</td>
              <td align="center">NA</td>
            </tr>
            <tr>
              <td rowspan="4" align="center">
                <bold>24 min</bold>
              </td>
              <td align="center"> </td>
              <td align="center">
                <bold>PAS</bold>
              </td>
              <td align="center">
                <bold>PAM</bold>
              </td>
              <td align="center">
                <bold>PAD</bold>
              </td>
              <td align="center">
                <bold>FC</bold>
              </td>
              <td align="center">
                <bold>DP</bold>
              </td>
            </tr>
            <tr>
              <td align="center">EC (n = 10)</td>
              <td align="center">163<xref ref-type="table-fn" rid="t01-fn02">#</xref>
                        &#177; 15,9</td>
              <td align="center">112,4 &#177; 8,9</td>
              <td align="center">69,5<xref ref-type="table-fn" rid="t01-fn01">*</xref>
                        &#177; 10,4</td>
              <td align="center">446,4<xref ref-type="table-fn" rid="t01-fn02">#</xref>
                        &#177; 41,7</td>
              <td align="center">73343,9<xref ref-type="table-fn" rid="t01-fn02">#</xref>
                        &#177; 10333,4</td>
            </tr>
            <tr>
              <td align="center">EI (n = 10)</td>
              <td align="center">156,2<xref ref-type="table-fn" rid="t01-fn02">#</xref>
                        &#177; 16,1</td>
              <td align="center">114,1 &#177; 11,3</td>
              <td align="center">80,8 &#177; 9,9</td>
              <td align="center">428,3 &#177; 40,1</td>
              <td align="center">67420,6<xref ref-type="table-fn" rid="t01-fn01">*</xref>
                        &#177; 12530,3</td>
            </tr>
            <tr>
              <td align="center">C (n = 10)</td>
              <td align="center">NA</td>
              <td align="center">NA</td>
              <td align="center">NA</td>
              <td align="center">NA</td>
              <td align="center">NA</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn>
            <p>Resultados em m&#233;dia &#177; desvio-padr&#227;o; EC: exerc&#237;cio cont&#237;nuo; EI:
                     exerc&#237;cio intervalado; C: controle; PAS: press&#227;o arterial sist&#243;lica (em mmHg);
                     PAM: press&#227;o arterial m&#233;dia (em mmHg); PAD: press&#227;o arterial diast&#243;lica (em
                     mmHg); FC: frequ&#234;ncia card&#237;aca (em bpm); DP: duplo produto (em bpm.mmHg); NA:
                     n&#227;o avaliado;</p>
          </fn>
          <fn id="t01-fn01">
            <label>*</label>
            <p>p &lt; 0,05 vs basal intragrupo;</p>
          </fn>
          <fn id="t01-fn02">
            <label>#</label>
            <p>p &lt; 0,01 vs basal intragrupo.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>Quanto ao efeito subagudo no grupo EC, a PA sist&#243;lica foi estaticamente menor nos
            minutos 115 (121,2 &#177; 5,9 mmHg, p = 0,04) e 120 (120,3 &#177; 7,5 mmHg, p = 0,03) e o DP nos
            minutos 55 (44875,5 &#177; 4925,4 mmHg.bpm, p &lt; 0,05), 75 (45153,5 &#177; 4937,8 mmHg, p &lt;
            0,05) e 115 (43098,2 &#177; 4318,7 mmHg.bpm, p &lt; 0,01) em compara&#231;&#227;o ao repouso. No grupo
            EI, a PA sist&#243;lica estava estatisticamente reduzida nos minutos 50 (120,2 &#177; 12,2 mmHg, p
            = 0,03), 55 (118,2 &#177; 13,9 mmHg, p = 0,02) e 60 (118,0 &#177; 15,5 mmHg, p = 0,03) enquanto a
            PA m&#233;dia foi estatisticamente reduzida nos minutos 55 (100,1 &#177; 8,3 mmHg, p = 0,03) e 60
            (101,0 &#177; 7,8 mmHg, p = 0,04) em rela&#231;&#227;o ao repouso. Al&#233;m disso, a FC e o DP estavam
            estatisticamente reduzidos nos minutos 55 e 45, respectivamente, at&#233; o final da an&#225;lise,
            ou seja, 120 min.</p>
      <p>Finalmente, o grupo C n&#227;o diferiu estatisticamente em nenhum par&#226;metro hemodin&#226;mico nem
            durante, nem ap&#243;s a sess&#227;o controle, em rela&#231;&#227;o a medida inicial.</p>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>O principal achado do estudo a ser destacado foi o aumento similar obtido durante a
            sess&#227;o intervalada nos par&#226;metros hemodin&#226;micos e maior redu&#231;&#227;o na FC e DP na
            recupera&#231;&#227;o em rela&#231;&#227;o &#224; sess&#227;o cont&#237;nua. H&#225; um ac&#250;mulo de evid&#234;ncias sugerindo que a
            magnitude dos benef&#237;cios advindos do exerc&#237;cio f&#237;sico aumenta proporcionalmente de
            acordo com a intensidade de cada sess&#227;o de exerc&#237;cio que constitui o programa de
               treinamento<xref ref-type="bibr" rid="B05">5</xref>. Dessa forma, o princ&#237;pio do
            exerc&#237;cio intervalado &#233; acumular mais tempo em zonas de intensidade superiores comparado
            ao exerc&#237;cio cont&#237;nuo, sem causar exaust&#227;o devido &#224; altern&#226;ncia de per&#237;odos de
            recupera&#231;&#227;o com intensidades mais baixas<xref ref-type="bibr" rid="B03">3</xref>. V&#225;rios
            estudos pr&#233;vios, indicam que o exerc&#237;cio intermitente induz maior aumento no
               VO<sub>2pico</sub><xref ref-type="bibr" rid="B14">14</xref>, nas adapta&#231;&#245;es
               musculares<xref ref-type="bibr" rid="B06">6</xref>, colesterol-HDL<xref ref-type="bibr" rid="B14">14</xref> e maior redu&#231;&#227;o na PA basal<xref ref-type="bibr" rid="B07">7</xref>, em indiv&#237;duos saud&#225;veis e pacientes, tais como hipertensos e com
            insufici&#234;ncia card&#237;aca. De fato, a prescri&#231;&#227;o de exerc&#237;cio intervalado tem aumentado
            exponencialmente em um per&#237;odo de tempo relativamente curto, especialmente na
            reabilita&#231;&#227;o card&#237;aca<xref ref-type="bibr" rid="B08">8</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref>. No entanto, tal metodologia de exerc&#237;cio, que
            consiste em per&#237;odos de intensidade mais alta, poderia promover aumento na carga de
            trabalho do mioc&#225;rdio, aumentando, portanto, a preocupa&#231;&#227;o acerca da seguran&#231;a do
            exerc&#237;cio.</p>
      <p>De acordo com os nossos resultados, o exerc&#237;cio intervalado n&#227;o promoveu nenhum aumento
            adicional de sobrecarga card&#237;aca comparado a uma sess&#227;o cont&#237;nua, uma vez que ambas as
            metodologias induziram aumentos similares na PA sist&#243;lica e DP. Resultados similares
            foram encontrados por Gayda e cols.<xref ref-type="bibr" rid="B09">9</xref>, ao comparar
            altera&#231;&#245;es hemodin&#226;micas centrais, medidas por bioimped&#226;ncia card&#237;aca, durante exerc&#237;cio
            intermitente e cont&#237;nuo em 13 pacientes com insufici&#234;ncia card&#237;aca. Comparado ao
            exerc&#237;cio cont&#237;nuo, a sess&#227;o intervalada promoveu aumento similar no d&#233;bito card&#237;aco
            m&#233;dio (9,26 &#177; 1,93 <italic>vs</italic> 10,06 &#177; 3,14 L/min) e no volume sist&#243;lico m&#233;dio
            (96 &#177; 22 <italic>vs</italic> 93 &#177; 21 mL).</p>
      <p>Em nosso estudo, tamb&#233;m foram evidenciadas redu&#231;&#245;es significativas na FC e DP ap&#243;s a
            sess&#227;o intermitente. Esse novo achado poderia ser justificado por uma poss&#237;vel melhora
            no equil&#237;brio simpatovagal ap&#243;s a sess&#227;o de exerc&#237;cio intervalado, o que pode
            representar um efeito cardioprotetor. Esse resultado foi corroborado por Labrunee e
               cols.<xref ref-type="bibr" rid="B15">15</xref>, em estudo que realizou Holter de 24 h
            em tr&#234;s dias consecutivos em 12 pacientes com insufici&#234;ncia card&#237;aca: ap&#243;s sess&#227;o de
            exerc&#237;cio intervalado, ap&#243;s cont&#237;nuo moderado e ap&#243;s um per&#237;odo controle sem atividade
            f&#237;sica. Interessantemente, foi encontrada maior redu&#231;&#227;o na FC e melhora nos &#237;ndices de
            variabilidade da FC ap&#243;s a sess&#227;o intervalada em rela&#231;&#227;o a sess&#227;o cont&#237;nua. Os autores
            tamb&#233;m mostraram que o n&#250;mero de contra&#231;&#245;es ventriculares prematuras e epis&#243;dios de
            taquicardia ventricular n&#227;o sustentada foram claramente e significativamente menores
            ap&#243;s o exerc&#237;cio intervalado, comparado ao cont&#237;nuo e sem exerc&#237;cio.</p>
      <p>Tamb&#233;m &#233; digno de nota que a PA sist&#243;lica foi reduzida no per&#237;odo de recupera&#231;&#227;o no
            grupo EI (50, 55 e 60 minutos) e EC (115 e 120 minutos). Ao final do per&#237;odo avaliado,
            em ambas as metodologias, a PA sist&#243;lica ainda n&#227;o apresentava valor est&#225;vel. Parece-nos
            que, se o per&#237;odo de recupera&#231;&#227;o fosse mais longo, talvez a PA sist&#243;lica apresentasse
            valores ainda menores. Poucos estudos demonstraram Hipotens&#227;o P&#243;s-Exerc&#237;cio (HPE) em
            indiv&#237;duos normotensos<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref>, enquanto v&#225;rios mostraram HPE em
               hipertensos<xref ref-type="bibr" rid="B18">18</xref><sup>-</sup><xref ref-type="bibr" rid="B20">20</xref> e ratos espontaneamente hipertensos<xref ref-type="bibr" rid="B21">21</xref><sup>-</sup><xref ref-type="bibr" rid="B24">24</xref>.</p>
      <p>Apesar dos nossos achados, &#233; necess&#225;rio um n&#250;mero maior de estudos, inclusive mais
            extensos para estabelecer de fato, a seguran&#231;a e efic&#225;cia do exerc&#237;cio intervalado,
            principalmente em cardiopatas. Tamb&#233;m deve ser destacado que nosso estudo foi
            desenvolvido em modelo experimental e a aplicabilidade desses resultados na cl&#237;nica deve
            ser feita com extrema cautela. Novos estudos experimentais se fazem necess&#225;rios para que
            sirvam como base de compara&#231;&#227;o aos resultados aqui encontrados. Avalia&#231;&#245;es de sobrecarga
            card&#237;aca, incluindo monitora&#231;&#227;o de FC e PA, durante e ap&#243;s realiza&#231;&#227;o de exerc&#237;cio
            f&#237;sico, podem promover mais seguran&#231;a para a prescri&#231;&#227;o de exerc&#237;cios, especialmente
            quando indiv&#237;duos com riscos cardiovasculares est&#227;o envolvidos. </p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#227;o</title>
      <p>Sess&#245;es de exerc&#237;cio aer&#243;bio intervalado em uma intensidade relativamente mais alta
            sugerem envolver maior redu&#231;&#227;o da FC e DP imediatamente ap&#243;s o t&#233;rmino do exerc&#237;cio
            comparado ao exerc&#237;cio cont&#237;nuo de intensidade moderada em ratos sadios.</p>
    </sec>
    <sec>
      <title>Contribui&#231;&#227;o dos autores</title>
      <p>Concep&#231;&#227;o e desenho da pesquisa: Massan GS, Lessa MAR. Obten&#231;&#227;o de dados: Masson GS.
            An&#225;lise e interpreta&#231;&#227;o dos dados: Borges JP, Masson GS, Lessa MA. An&#225;lise estat&#237;stica:
            Borges JP, Masson GS, Lessa MA. Obten&#231;&#227;o de financiamento: Tibiri&#231;&#225; E, Lessa MA. Reda&#231;&#227;o
            do manuscrito: Borges JP, Tibiri&#231;&#225; E, Lessa MA. Revis&#227;o cr&#237;tica do manuscrito quanto ao
            conte&#250;do intelectual: Borges JP, Tibiri&#231;&#225; EV, Lessa MA.</p>
    </sec>
  </body>
  <back>
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    <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">Aerobic Interval Exercise Training Induces Greater
               Reduction in Cardiac Workload in the Recovery Period in Rats</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Borges</surname>
            <given-names>Juliana Pereira</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
          <xref ref-type="corresp" rid="c02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Masson</surname>
            <given-names>Gustavo Santos</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Tibiri&#231;&#225;</surname>
            <given-names>Eduardo</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lessa</surname>
            <given-names>Marcos Adriano</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <aff id="aff02">
          <institution content-type="orgname">Instituto Oswaldo Cruz</institution>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country>Brazil</country>
          <institution content-type="original">Instituto Oswaldo Cruz - FIOCRUZ, Rio de
                  Janeiro, RJ - Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c02"><bold>Mailing Address: Juliana Pereira Borges</bold>, Av. Brasil 4365, Manguinhos.
               Postal Code 21040-900, Rio de Janeiro, RJ - Brazil. E-mail:
                  <email>julipborges@gmail.com</email></corresp>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <abstract xml:lang="en">
        <sec>
          <title>Background:</title>
          <p> Aerobic interval exercise training has greater benefits on cardiovascular
                  function as compared with aerobic continuous exercise training. </p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p> The present study aimed at analyzing the effects of both exercise modalities on
                  acute and subacute hemodynamic responses of healthy rats. </p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p> Thirty male rats were randomly assigned into three groups as follows: continuous
                  exercise (CE, n = 10); interval exercise (IE, n = 10); and control (C, n = 10).
                  Both IE and CE groups performed a 30-minute exercise session. The IE group session
                  consisted of three successive 4-minute periods at 60% of maximal velocity (Max
                  Vel), with 4-minute recovery intervals at 40% of Max Vel. The CE group ran
                  continuously at 50% of Max Vel. Heart rate (HR), blood pressure(BP), and rate
                  pressure product (RPP) were measured before, during and after the exercise
                  session. </p>
        </sec>
        <sec>
          <title>Results:</title>
          <p> The CE and IE groups showed an increase in systolic BP and RPP during exercise as
                  compared with the baseline values. After the end of exercise, the CE group showed
                  a lower response of systolic BP and RPP as compared with the baseline values,
                  while the IE group showed lower systolic BP and mean BP values. However, only the
                  IE group had a lower response of HR and RPP during recovery. </p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p> In healthy rats, one interval exercise session, as compared with continuous
                  exercise, induced similar hemodynamic responses during exercise. However, during
                  recovery, the interval exercise caused greater reductions in cardiac workload than
                  the continuous exercise.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Blood pressure</kwd>
        <kwd>Exercise acute effects</kwd>
        <kwd>Intermittent exercise</kwd>
      </kwd-group>
      <counts>
        <fig-count count="2"/>
        <table-count count="1"/>
        <equation-count count="0"/>
        <ref-count count="24"/>
        <page-count count="7"/>
      </counts>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Aerobic interval or intermittent training, originally used by athletes, consists of
               alternated bouts of high- and low-intensity exercises<xref ref-type="bibr" rid="B01">1</xref><sup>-</sup><xref ref-type="bibr" rid="B04">4</xref>. There is a body of
               evidence suggesting that the magnitude of the benefits originating from physical
               exercise increases proportionally with the intensity of each exercise session that
               constitutes the exercise training program<xref ref-type="bibr" rid="B05">5</xref>.
               The effects observed on the cardiorespiratory and muscular function have led
               researchers to consider the practice of interval exercise in the field of
               cardiovascular diseases<xref ref-type="bibr" rid="B01">1</xref>. Gibala et al<xref ref-type="bibr" rid="B06">6</xref> have shown that interval exercise training is
               more efficient in inducing rapid adaptations in skeletal muscles and exercise
               performance as compared with continuous training. At a markedly smaller training
               volume, interval exercise promotes benefits in the exercise capacity and expression
               of antioxidant enzymes similar to those observed in traditional conservative
               trainings of continuous exercise<xref ref-type="bibr" rid="B06">6</xref>.
               Molmen-Hansen et al<xref ref-type="bibr" rid="B07">7</xref> have recently
               demonstrated that intermittent exercise sessions could reduce blood pressure (BP) and
               improve myocardial function of hypertensive patients. In addition, several previous
               studies had reported that interval training at a relatively higher intensity could be
               used in both clinical practice and experiments, and that such exercise modality had
               greater beneficial effects on the heart<xref ref-type="bibr" rid="B08">8</xref><sup>,</sup><xref ref-type="bibr" rid="B09">9</xref>. Those
               characteristics suggest that intermittent training can be more appropriate to
               individuals with metabolic syndrome, dyslipidemia and other cardiovascular risk
                  factors<xref ref-type="bibr" rid="B10">10</xref><sup>-</sup><xref ref-type="bibr" rid="B12">12</xref>. However, little is known about the acute and subacute
               differences obtained with that exercise modality as compared to traditional
               continuous training. The acute effect refers to the physiological response observed
               when exercise is performed [increase in heart rate (HR) and systolic BP]. However,
               the subacute effects occur immediately after finishing the training, and involve
               chronic physiological adaptations that develop over the training period<xref ref-type="bibr" rid="B13">13</xref>. Thus, such effects of interval and continuous
               exercise trainings should be further studied, considering that continuous and
               interval exercise trainings could promote different hemodynamic responses regarding
               kinetics and magnitude, especially important for cardiovascular impairment. The
               present study aimed at assessing the acute and subacute hemodynamic responses of both
               exercise modalities in rats.</p>
      </sec>
      <sec sec-type="methods">
        <title>Methods</title>
        <sec>
          <title>Animals</title>
          <p>All procedures performed were approved by the Committee on Ethics and Research of
                  the Funda&#231;&#227;o Oswaldo Cruz (protocol 31/10-3 LW21-10), according to the Helsinki
                  Declaration. There was no conflict of interest related to this study.</p>
          <p>During the experimental period, the animals were submitted to 12-hour light/dark
                  cycles under controlled temperature (22 &#177; 1&#186;C), and kept in boxes (three to four
                  animals per box). The animals received water and food preparation <italic>ad
                     libitum.</italic>
               </p>
          <p>Male Wistar rats (weight range, 300 and 350 g; minimum age, 180 days) were
                  randomly distributed into three groups as follows: continuous exercise (CE, n =
                  10); interval exercise (IE, n = 10); and control (C, n = 10).</p>
        </sec>
        <sec>
          <title>Exercise protocol</title>
          <p>The whole protocol comprised six consecutive days. All animals were adapted to
                  exercise treadmill (HT 2.0, Hectron Fitness Equipment, Rio de Janeiro, Brazil)
                  over three consecutive days (10 minutes at 10 m/min). On the fourth day, maximal
                  exercise test was performed to determine maximal velocity (Max Vel). The test
                  consisted of initial velocity of 5 m/min with 1.5-m/min velocity increase every 2
                  minutes up to exhaustion, when the animal remained on the shock grid despite the
                  sound stimulus. On the fifth day, the rats underwent the cannulation procedure
                  described in the following session. Finally, on the sixth day, the animals
                  underwent either exercise or control session. Both IE and CE groups underwent a
                  30-minute exercise training, including 3 minutes of warm-up and 3 minutes of
                  deceleration at 30% of Max Vel. The CE group session consisted of continuous
                  running at 50% of the Max Vel, while the IE group performed three successive
                  4-minute periods at 60% of Max Vel, with 4-minute intervals of recovery at 40% of
                  Max Vel. Such intensities were used to equalize the exercise session volume
                  between the groups, allowing their comparison. By maintaining mean intensity at
                  50% of Max Vel in both groups, the only difference would be the way of applying
                  intensity, that is, with intervals or not. Thus, the possible differences found
                  between the two groups could not be attributed to different exercise loads.</p>
        </sec>
        <sec>
          <title>Surgical procedure and hemodynamic measures</title>
          <p>All animals were anesthetized with pentobarbital (50 mg/kg ip) for polyethylene
                  cannula (PE-50 with saline-heparin solution) implantation in the left carotid
                  artery to directly measure BP and HR. The cannula was then exteriorized on the
                  animal's back, allowing 24-hour analysis for all three groups. Thus, the analysis
                  was performed while the animals were conscious and could move freely during the
                  experiment. </p>
          <p>To measure BP and HR, the cannula was connected to a pressure transducer (TSD104A,
                  BIOPAC Systems Inc, Goleta, CA, USA) and a signal amplifier (DA100C, BIOPAC
                  Systems Inc, Goleta, CA, USA). The measures were acquired at a sample rate of 200
                  samples/second by use of the MP150 system (BIOPAC Systems Inc, Goleta, CA, USA)
                  and recorded using a specific software (AcqKnowledge 3.7.3 for Windows, BIOPAC
                  Systems Inc, Goleta, CA, USA). The signals were recorded at rest (10 minutes),
                  during exercise (every 8 minutes excluding warm-up and deceleration), and up to 90
                  minutes after ending the exercise (1 minute every 5 minutes). The signals were
                  analyzed beat-to-beat to quantify changes in BP and HR. Rate pressure product
                  (RPP), considered an estimation of myocardial workload, was calculated by
                  multiplying HR by systolic BP.</p>
        </sec>
        <sec>
          <title>Statistical analysis</title>
          <p>Differences between the groups were analyzed by using two-way ANOVA for repeated
                  measures, followed by Bonferroni post-test. The significance level of 5% was
                  adopted. All results were expressed as mean &#177; standard deviation. The statistical
                  analyses were performed with the GraphPad Prism software (Version 5 for Windows,
                  GraphPad Software, Inc, La Jolla, CA, USA).</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Results</title>
        <p>The groups had no statistical difference regarding body weight (CE: 377.5 &#177; 16; IE:
               374.4 &#177; 18; C: 378.3 &#177; 15 g) and hemodynamic measures at rest. In the maximal
               exercise test, no statistical difference was observed between the groups regarding
               Max Vel (CE: 20.5 &#177; 3; IE: 19.6 &#177; 2; C: 19.2 &#177; 1 m/min) and duration (CE: 1319.9 &#177;
               200; IE: 1204.5 &#177; 179; C: 1209.4 &#177; 105 sec).</p>
        <p>The acute and subacute effects on BP, HR and RPP in the different exercise modalities
               are shown in <xref ref-type="fig" rid="f03">Figures 1</xref> and <xref ref-type="fig" rid="f04">2</xref>, respectively.</p>
        <fig id="f03" fig-type="other">
          <label>Figure 1</label>
          <caption>
            <title>Systolic, mean and diastolic blood pressure during and after exercise
                     training. *p &lt; 0.05 vs. rest in the continuous group; #p &lt; 0.05 vs. rest
                     in the interval group.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-102-01-0047-30230-gf01-en.jpg"/></fig>
        <fig id="f04" fig-type="other">
          <label>Figure 2</label>
          <caption>
            <title>Heart rate and rate pressure product during and after exercise training. *p
                     &lt; 0.05 vs. rest in the continuous group; #p &lt; 0.05 vs. rest in the
                     interval group.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-102-01-0047-30230-gf02-en.jpg"/></fig>
        <p>Regarding the acute effect of exercise, the CE group had a statistically higher
               response after 8, 16 and 24 minutes of exercise for systolic BP, HR and RPP as
               compared with the baseline values (<xref ref-type="table" rid="t02">Table 1</xref>).
               In addition, the CE group had a statistically lower diastolic BP after 8, 16 and 24
               minutes of exercise as compared with rest values (<xref ref-type="table" rid="t02">Table 1</xref>). The IE group also had a statistically higher response after 8,
               16 and 24 minutes of exercise for systolic BP and RPP as compared with rest values,
               while diastolic BP was statistically reduced only after 8 minutes of exercise (<xref ref-type="table" rid="t02">Table 1</xref>).</p>
        <table-wrap id="t02">
          <label>Table 1</label>
          <caption>
            <title>Hemodynamic responses obtained at baseline and during physical exercise (8,
                     16 and 24 minutes) for the continuous, interval and control groups</title>
          </caption>
          <table frame="hsides" rules="rows">
            <tbody>
              <tr>
                <td rowspan="4" align="center">
                  <bold>Baseline</bold>
                </td>
                <td align="center"> </td>
                <td align="center">
                  <bold>SBP</bold>
                </td>
                <td align="center">
                  <bold>MBP</bold>
                </td>
                <td align="center">
                  <bold>DBP</bold>
                </td>
                <td align="center">
                  <bold>HR</bold>
                </td>
                <td align="center">
                  <bold>RPP</bold>
                </td>
              </tr>
              <tr>
                <td align="center">EC (n = 10)</td>
                <td align="center">132.4 &#177; 11.3</td>
                <td align="center">106.4 &#177; 7.2</td>
                <td align="center">86.2 &#177; 12.3</td>
                <td align="center">378.6 &#177; 28.3</td>
                <td align="center">51136.8 &#177; 5306.3</td>
              </tr>
              <tr>
                <td align="center">EI (n = 10)</td>
                <td align="center">133.5 &#177; 10.8</td>
                <td align="center">109.4 &#177; 7.3</td>
                <td align="center">84.7 &#177; 8.2</td>
                <td align="center">405.6 &#177; 44.7</td>
                <td align="center">54444.0 &#177; 9282.6</td>
              </tr>
              <tr>
                <td align="center">C (n = 10)</td>
                <td align="center">136.7 &#177; 15.9</td>
                <td align="center">110.9 &#177; 12.0</td>
                <td align="center">85.6 &#177; 10.8</td>
                <td align="center">387.4 &#177; 50.4</td>
                <td align="center">53161.5 &#177; 10232.5</td>
              </tr>
              <tr>
                <td rowspan="4" align="center">
                  <bold>8 min</bold>
                </td>
                <td align="center"> </td>
                <td align="center">
                  <bold>SBP</bold>
                </td>
                <td align="center">
                  <bold>MBP</bold>
                </td>
                <td align="center">
                  <bold>DBP</bold>
                </td>
                <td align="center">
                  <bold>HR</bold>
                </td>
                <td align="center">
                  <bold>RPP</bold>
                </td>
              </tr>
              <tr>
                <td align="center">EC (n = 10)</td>
                <td align="center">152.2<xref ref-type="table-fn" rid="t02-fn01">#</xref>
                           &#177; 11.4</td>
                <td align="center">109.7 &#177; 7.6</td>
                <td align="center">70.4<xref ref-type="table-fn" rid="t02-fn02">*</xref>
                           &#177; 12.6</td>
                <td align="center">438.5<xref ref-type="table-fn" rid="t02-fn01">#</xref>
                           &#177; 34.7</td>
                <td align="center">66593.9<xref ref-type="table-fn" rid="t02-fn01">#</xref>
                           &#177; 6773.5</td>
              </tr>
              <tr>
                <td align="center">EI (n = 10)</td>
                <td align="center">156.5<xref ref-type="table-fn" rid="t02-fn01">#</xref>
                           &#177; 15.8</td>
                <td align="center">112.4 &#177; 11.1</td>
                <td align="center">74.6<xref ref-type="table-fn" rid="t02-fn02">*</xref>
                           &#177; 11.5</td>
                <td align="center">442.5 &#177; 61.2</td>
                <td align="center">70002.4<xref ref-type="table-fn" rid="t02-fn02">*</xref>
                           &#177; 15835.7</td>
              </tr>
              <tr>
                <td align="center">C (n = 10)</td>
                <td align="center">NA</td>
                <td align="center">NA</td>
                <td align="center">NA</td>
                <td align="center">NA</td>
                <td align="center">NA</td>
              </tr>
              <tr>
                <td rowspan="4" align="center">
                  <bold>16 min</bold>
                </td>
                <td align="center"> </td>
                <td align="center">
                  <bold>SBP</bold>
                </td>
                <td align="center">
                  <bold>MBP</bold>
                </td>
                <td align="center">
                  <bold>DBP</bold>
                </td>
                <td align="center">
                  <bold>HR</bold>
                </td>
                <td align="center">
                  <bold>RPP</bold>
                </td>
              </tr>
              <tr>
                <td align="center">EC (n = 10)</td>
                <td align="center">154.8<xref ref-type="table-fn" rid="t02-fn01">#</xref>
                           &#177; 17.0</td>
                <td align="center">110.7 &#177; 8.0</td>
                <td align="center">72.1<xref ref-type="table-fn" rid="t02-fn02">*</xref>
                           &#177; 13.8</td>
                <td align="center">446.9<xref ref-type="table-fn" rid="t02-fn01">#</xref>
                           &#177; 33.8</td>
                <td align="center">68607.2<xref ref-type="table-fn" rid="t02-fn01">#</xref>
                           &#177; 7001.4</td>
              </tr>
              <tr>
                <td align="center">EI (n = 10)</td>
                <td align="center">153.4<xref ref-type="table-fn" rid="t02-fn01">#</xref>
                           &#177; 15.8</td>
                <td align="center">112.8 &#177; 10.4</td>
                <td align="center">76.9 &#177; 11.5</td>
                <td align="center">441.4 &#177; 49.2</td>
                <td align="center">68342.1<xref ref-type="table-fn" rid="t02-fn02">*</xref>
                           &#177; 13838.3</td>
              </tr>
              <tr>
                <td align="center">C (n = 10)</td>
                <td align="center">NA</td>
                <td align="center">NA</td>
                <td align="center">NA</td>
                <td align="center">NA</td>
                <td align="center">NA</td>
              </tr>
              <tr>
                <td rowspan="4" align="center">
                  <bold>24 min</bold>
                </td>
                <td align="center"> </td>
                <td align="center">
                  <bold>SBP</bold>
                </td>
                <td align="center">
                  <bold>MBP</bold>
                </td>
                <td align="center">
                  <bold>DBP</bold>
                </td>
                <td align="center">
                  <bold>HR</bold>
                </td>
                <td align="center">
                  <bold>RPP</bold>
                </td>
              </tr>
              <tr>
                <td align="center">EC (n = 10)</td>
                <td align="center">163<xref ref-type="table-fn" rid="t02-fn01">#</xref>
                           &#177; 15.9</td>
                <td align="center">112.4 &#177; 8.9</td>
                <td align="center">69.5<xref ref-type="table-fn" rid="t02-fn02">*</xref>
                           &#177; 10.4</td>
                <td align="center">446.4<xref ref-type="table-fn" rid="t02-fn01">#</xref>
                           &#177; 41.7</td>
                <td align="center">73343.9<xref ref-type="table-fn" rid="t02-fn01">#</xref>
                           &#177; 10333.4</td>
              </tr>
              <tr>
                <td align="center">EI (n = 10)</td>
                <td align="center">156.2<xref ref-type="table-fn" rid="t02-fn01">#</xref>
                           &#177; 16.1</td>
                <td align="center">114.1 &#177; 11.3</td>
                <td align="center">80.8 &#177; 9.9</td>
                <td align="center">428.3 &#177; 40.1</td>
                <td align="center">67420.6<xref ref-type="table-fn" rid="t02-fn02">*</xref>
                           &#177; 12530.3</td>
              </tr>
              <tr>
                <td align="center">C (n = 10)</td>
                <td align="center">NA</td>
                <td align="center">NA</td>
                <td align="center">NA</td>
                <td align="center">NA</td>
                <td align="center">NA</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn>
              <p>Results shown as mean &#177; standard deviation; CE: continuous exercise; IE:
                        interval exercise; C: control; SBP: systolic blood pressure (mm Hg); MBP:
                        mean blood pressure (mm Hg); DBP: diastolic blood pressure (mm Hg); HR:
                        heart rate (bpm); RPP: rate pressure product (bpm.mm Hg); NA: not assessed;
                     </p>
            </fn>
            <fn id="t02-fn01">
              <label>*</label>
              <p>p &lt; 0.05 vs intragroup baseline;</p>
            </fn>
            <fn id="t02-fn02">
              <label>#</label>
              <p>p &lt; 0.01 vs intragroup baseline.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Regarding the subacute effect of exercise in the CE group, statically lower values
               were observed as follows: of systolic BP, at minutes 115 (121.2 &#177; 5.9 mmHg, p = 0.04)
               and 120 (120.3 &#177; 7.5 mmHg, p = 0.03); of RPP, at minutes 55 (44875.5 &#177; 4925.4
               mmHg.bpm, p &lt; 0.05), 75 (45153.5 &#177; 4937.8 mm Hg, p &lt; 0.05) and 115 (43098.2 &#177;
               4318.7 mmHg.bpm, p &lt; 0.01) as compared to rest values. In the IE group, systolic
               BP was statistically reduced at minutes 50 (120.2 &#177; 12.2 mmHg, p = 0.03), 55 (118.2 &#177;
               13.9 mm Hg, p = 0.02) and 60 (118.0 &#177; 15.5 mmHg, p = 0.03), while mean BP was
               statistically reduced at minutes 55 (100.1 &#177; 8.3 mmHg, p = 0.03) and 60 (101.0 &#177; 7.8
               mmHg, p = 0.04) as compared to rest values. In addition, HR and RPP were
               statistically reduced at minutes 55 and 45, respectively, until the end of the
               analysis (120 minutes).</p>
        <p>Finally, the C group showed no statistic difference in any hemodynamic parameter
               neither during, nor after the control session, as compared to the initial measure.
            </p>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>The major finding of this study was as follows: similarity of the increase in the
               hemodynamic parameters obtained during the interval exercise session and greater
               reduction in HR and RPP in the recovery period as compared with those of the
               continuous exercise session. There is a body of evidence suggesting that the
               magnitude of the benefits originating from physical exercise increases proportionally
               with the intensity of each exercise session that constitutes the exercise training
                  program<xref ref-type="bibr" rid="B05">5</xref>. Thus, the principle of the
               interval exercise is to spend more time in higher intensity zones as compared with
               continuous exercise, without causing exhaustion due to alternation of lower-intensity
               recovery periods<xref ref-type="bibr" rid="B03">3</xref>. Several previous studies
               have reported that intermittent exercise induces greater increase in
                  VO<sub>2peak</sub>
               <xref ref-type="bibr" rid="B14">14</xref>, in muscular adaptations<xref ref-type="bibr" rid="B06">6</xref>, HDL-cholesterol<xref ref-type="bibr" rid="B14">14</xref> and greater reduction in baseline BP<xref ref-type="bibr" rid="B07">7</xref>, in healthy individuals and patients, such as those with hypertension
               and heart failure. In fact, the prescription of interval exercise has exponentially
               increased over a relatively short period of time, especially in cardiac
                  rehabilitation<xref ref-type="bibr" rid="B08">8</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref>. However, that exercise modality, consisting
               of higher-intensity periods, could promote an increase in myocardial workload,
               therefore increasing concern with exercise safety.</p>
        <p>According to our results, the interval exercise promoted no additional increase in
               cardiac workload as compared with continuous exercise, since both modalities induced
               similar increases in systolic BP and RPP. Similar results have been found by Gayda et
                  al<xref ref-type="bibr" rid="B09">9</xref>, when comparing central hemodynamic
               changes, measured by use of cardiac bioimpedance, during intermittent and continuous
               exercise in 13 patients with heart failure. Compared with continuous exercise,
               interval exercise promoted a similar increase in mean cardiac output (9.26 &#177; 1.93
                  <italic>vs</italic> 10.06 &#177; 3.14 L/min) and mean systolic volume (96 &#177; 22
                  <italic>vs</italic> 93 &#177; 21 mL).</p>
        <p>In our study, significant reductions have also been evidenced in HR and RPP after the
               intermittent session. That new finding could be justified by a possible improvement
               in the sympathovagal balance after the interval exercise session, which might
               represent a cardioprotective effect. That result has been corroborated by Labrunee et
                  al<xref ref-type="bibr" rid="B15">15</xref> performing 24-hour Holter on three
               consecutive days in 12 patients with heart failure: after the interval exercise
               session; after moderate continuous exercise; and after a control period with no
               physical activity. Interestingly, a greater reduction in HR and an improvement in HR
               variability indices were found after the interval exercise session as compared with
               the continuous exercise session. The authors have also reported that the numbers of
               premature ventricular contractions and non-sustained ventricular tachycardia episodes
               were clearly and significantly lower after interval exercise as compared with
               continuous exercise or no exercise.</p>
        <p>It is also worth noting that systolic BP was reduced in the recovery period in the IE
               group (50, 55 and 60 minutes) and CE (115 and 120 minutes). At the end of the period
               assessed, for both exercise modalities, systolic BP was not yet stable. It seems
               that, if the recovery period were longer, systolic BP might even show lower values. A
               few studies have demonstrated post-exercise hypotension (PEH) in normotensive
                  individuals<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref>, while others have shown PEH in hypertensive
                  individuals<xref ref-type="bibr" rid="B18">18</xref><sup>-</sup><xref ref-type="bibr" rid="B20">20</xref> and spontaneously hypertensive rats<xref ref-type="bibr" rid="B21">21</xref><sup>-</sup><xref ref-type="bibr" rid="B24">24</xref>.</p>
        <p>A larger number of studies, in addition to more extensive ones, are required to
               establish the real safety and efficacy of interval exercise, mainly in patients with
               heart disease. It is worth noting that our study was performed in an experimental
               model, and the application of its results in clinical practice should be extremely
               cautious. New experimental studies are necessary to serve as comparison base with our
               results. Assessments on cardiac workload, including HR and BP monitoring, during and
               after physical exercise practice, can increase the safety of exercise prescription,
               especially when involving individuals at cardiovascular risk.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusion</title>
        <p>Aerobic interval exercise sessions of a relatively higher intensity suggest a higher
               reduction in HR and RPP immediately after finishing exercise as compared with
               continuous exercise of moderate intensity in healthy rats.</p>
      </sec>
      <sec>
        <title>Author contributions</title>
        <p>Conception and design of the research: Masson GS, Lessa MA. Acquisition of data:
               Masson GS. Analysis and interpretation of the data: Borges JP, Masson GS, Lessa MA.
               Statistical analysis: Borges JP, Masson GS, Lessa MA. Obtaining funding: Tibiri&#231;&#225; E,
               Lessa MA. Writing of the manuscript: Borges JP, Tibiri&#231;&#225; E, Lessa MA. Critical
               revision of the manuscript for intellectual content: Borges JP, Tibiri&#231;&#225; E, Lessa
               MA.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <p>
            <bold>Study Association</bold>
          </p>
          <p>This study is not associated with any post-graduation program.</p>
        </fn>
        <fn fn-type="financial-disclosure">
          <p>
            <bold>Sources of Funding</bold>
          </p>
          <p>This study was funded by CNPq, FAPERJ e FIOCRUZ.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
