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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">fScfgmfZ88dzM4hYD4tv3Jh</article-id>
      <article-id pub-id-type="other">00014</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2007001400014</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(07)08900214</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2007001400014</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Relato de Caso</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Transplante de C&#233;lulas-tronco marcadas para o mioc&#225;rdio de paciente com doen&#231;a de chagas</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Jacob</surname>
            <given-names>Jos&#233; Luiz Balthazar</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Salis</surname>
            <given-names>Fernando Vilela</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ruiz</surname>
            <given-names>Milton A.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Greco</surname>
            <given-names>Oswaldo Tadeu</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">S&#227;o Jos&#233; do Rio Preto</named-content>
          <named-content content-type="state"/>
        </addr-line>
        <institution content-type="orgname">Instituto de Mol&#233;stias Cardiovasculares</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>08</month>
        <year>2007</year>
      </pub-date>
      <volume>89</volume>
      <issue>2</issue>
      <fpage>e10</fpage>
      <lpage>e11</lpage>
      <history>
        <date date-type="received">
          <day>24</day>
          <month>11</month>
          <year>2006</year>
        </date>
        <date date-type="rev-recd">
          <day>01</day>
          <month>03</month>
          <year>2007</year>
        </date>
        <date date-type="accepted">
          <day>03</day>
          <month>04</month>
          <year>2007</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>O transplante de c&#233;lulas-tronco &#233; uma nova terapia com objetivo de produzir regenera&#231;&#227;o card&#237;aca pela diferencia&#231;&#227;o ou aumento dos mi&#243;citos card&#237;acos ou prolifera&#231;&#227;o neovascular em pacientes no est&#225;gio final de insufici&#234;ncia card&#237;aca congestiva secund&#225;ria a cardiomiopatia dilatada&#185;, mas os resultados s&#227;o desconhecidos2,3.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Transplante de c&#233;lulas-tronco</kwd>
        <kwd>cardiomiopatia chag&#225;sica</kwd>
        <kwd>doen&#231;a de Chagas</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>05</day>
        <month>09</month>
        <year>2007</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>RELATO DE CASO</bold>
    </p>
    <p>Transplante de C&#233;lulas-tronco marcadas para o mioc&#225;rdio de paciente com doen&#231;a de chagas</p>
    <p>
      <bold>Jos&#233; Luiz Balthazar Jacob; Fernando Vilela Salis; Milton A. Ruiz; Oswaldo Tadeu Greco</bold>
    </p>
    <p> Instituto de Mol&#233;stias Cardiovasculares (IMC) de S&#227;o Jos&#233; do Rio Preto - S&#227;o Jos&#233; do Rio Preto, SP - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="end">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p>O transplante de c&#233;lulas-tronco &#233; uma nova terapia com objetivo de produzir regenera&#231;&#227;o card&#237;aca pela diferencia&#231;&#227;o ou aumento dos mi&#243;citos card&#237;acos ou prolifera&#231;&#227;o neovascular em pacientes no est&#225;gio final de insufici&#234;ncia card&#237;aca congestiva secund&#225;ria a cardiomiopatia dilatada<sup>1</sup>, mas os resultados s&#227;o desconhecidos<sup>2,3</sup>.</p>
    <p><bold>Palavras-chave:</bold> Transplante de c&#233;lulas-tronco, cardiomiopatia chag&#225;sica, doen&#231;a de Chagas.</p>
    <p>
      <bold>Relato do Caso</bold>
    </p>
    <p>Paciente de 50 anos de idade, do sexo masculino, com insufici&#234;ncia card&#237;aca refrat&#225;ria secund&#225;ria &#224; cardiomiopatia dilatada por doen&#231;a de Chagas, foi encaminhado ao nosso Instituto, que &#233; autorizado pelo Minist&#233;rio da Sa&#250;de do Brasil para terapia com c&#233;lulas-tronco em cardiomiopatia dilatada, doen&#231;a de Chagas e infarto agudo do mioc&#225;rdio.</p>
    <p>O estudo de perfus&#227;o mioc&#225;rdica com 99 mTc SESTAMIBI mostrava largas &#225;reas de hipocapta&#231;&#227;o em paredes anterior, apical e septal do ventr&#237;culo esquerdo (<xref ref-type="fig" rid="fig01">fig. 1</xref>). O cateterismo card&#237;aco revelou grave disfun&#231;&#227;o ventricular esquerda (fra&#231;&#227;o de eje&#231;&#227;o = 15,3%) e art&#233;rias coron&#225;rias normais. Apesar da otimiza&#231;&#227;o da terap&#234;utica medicamentosa, houve pobre resposta cl&#237;nica. O paciente foi informado sobre os poss&#237;veis riscos e benef&#237;cios do tratamento com transplante de c&#233;lulas-tronco e assinou o Termo de Consentimento Autorizado.</p>
    <fig id="fig01">
      <graphic xlink:href="1678-4170-abc-89-02-0e10-00014-gf01.jpg"/></fig>
    <p>Ap&#243;s aprova&#231;&#227;o pelo Comit&#234; de &#201;tica em Pesquisa, o paciente foi submetido ao transplante de c&#233;lulas-tronco.</p>
    <p>O paciente recebeu anestesia peridural, e c&#233;lulas da medula &#243;ssea foram obtidas por pun&#231;&#245;es da crista il&#237;aca. Vinte mililitros de suspens&#227;o de c&#233;lulas mononucleares foram obtidos usando a t&#233;cnica descrita na literatura<sup>1</sup>. Tr&#234;s mililitros de suspens&#227;o foram marcados com 99mTc HMPAO. A suspens&#227;o de c&#233;lulas mononucleares foi lentamente injetada (1 ml/minuto) nas art&#233;rias coron&#225;rias. Foram injetados 50% de suspens&#227;o na art&#233;ria descendente anterior, 25% na art&#233;ria circunflexa esquerda e 25% na art&#233;ria coron&#225;ria direita. As c&#233;lulas marcadas com 99 mTc HMPAO foram injetadas apenas na art&#233;ria descendente anterior. Novos estudos cintilogr&#225;ficos foram realizados 2 horas e 6 horas ap&#243;s o procedimento, respectivamente.</p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>Em pacientes em que o transplante de c&#233;lulas-tronco &#233; indicado para tratamento do est&#225;gio final da cardiomiopatia dilatada, se as art&#233;rias coron&#225;rias forem normais, a infus&#227;o seletiva da suspens&#227;o de c&#233;lulas mononucleares nas art&#233;rias descendente anterior, circunflexa esquerda e coron&#225;ria direita &#233; nossa t&#233;cnica preferida. A infus&#227;o da suspens&#227;o &#233; feita sempre na extremidade distal do ter&#231;o proximal das art&#233;rias coron&#225;rias, com comprova&#231;&#227;o de aus&#234;ncia de fluxo retr&#243;grado pela inje&#231;&#227;o pr&#233;via de contraste atrav&#233;s do cateter de infus&#227;o.</p>
    <p>Existiam, entretanto, d&#250;vidas se as c&#233;lulas eram retidas no m&#250;sculo card&#237;aco. Por essa raz&#227;o, foi realizada a infus&#227;o de c&#233;lulas mononucleares marcadas com 99 mTc HMPAO, usando a t&#233;cnica intracoron&#225;ria descrita anteriormente.</p>
    <p>Estudos de perfus&#227;o mioc&#225;rdica foram repetidos para analisar os mesmos eixos, duas horas e seis horas, respectivamente, ap&#243;s o transplante por via intracoron&#225;ria de c&#233;lulas mononucleares marcadas, e revelaram sua capta&#231;&#227;o e reten&#231;&#227;o em &#225;reas que previamente n&#227;o captavam SESTAMIBI (<xref ref-type="fig" rid="fig01">fig. 1</xref>). A imagem cintilogr&#225;fica de corpo inteiro mostrava que o restante das c&#233;lulas mononucleares era captado principalmente pelo f&#237;gado e ba&#231;o (<xref ref-type="fig" rid="fig02">fig. 2</xref>).</p>
    <fig id="fig02">
      <graphic xlink:href="1678-4170-abc-89-02-0e10-00014-gf02.jpg"/></fig>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>O caso relatado mostra que, ap&#243;s infus&#227;o de c&#233;lulas mononucleares pela t&#233;cnica intracoron&#225;ria, significativa quantidade dessas c&#233;lulas &#233; atra&#237;da para &#225;reas previamente n&#227;o-captantes do mioc&#225;rdio e nelas retidas (provavelmente mioc&#225;rdio fibr&#243;tico).</p>
    <p>Em nosso conhecimento, esse &#233; o primeiro relato na literatura desses achados na doen&#231;a de Chagas.</p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflitos 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 desse estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <p>Correspond&#234;ncia:</p>
        <p> Jos&#233; Luiz Balthazar Jacob </p>
        <p> IMC </p>
        <p> Rua Castelo D'Agua, 3030 </p>
        <p> 15015-210 - S&#227;o Jos&#233; do Rio Preto, SP - Brasil </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="jljacob@cardiol.br">jljacob@cardiol.br</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 24/11/06; revisado recebido em 01/03/07; aceito em 03/04/07</p>
  </body>
  <back>
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          <fpage>185</fpage>
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            </name>
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              <surname>Feitosa</surname>
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            </name>
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              <surname>Soares</surname>
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            </name>
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              <surname>Pinto</surname>
              <given-names>JA F&#186;</given-names>
            </name>
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              <surname>Mota</surname>
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            </name>
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              <surname>Almeida</surname>
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        <mixed-citation>2. Strauer BE, Brehm M, Zeus T, Bartsch T,    Schannuel C, Antke C, et al. Regeneration of human infarcted heart muscle by    intracoronary autologous bone marrow cell transplantation in chronic coronary    artery disease: The IACT Study. J Am Coll Cardiol.2005;46 (9): 1651-8.</mixed-citation>
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              <surname>Brehm</surname>
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              <surname>Zeus</surname>
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            </name>
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              <surname>Bartsch</surname>
              <given-names>T</given-names>
            </name>
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              <surname>Schannuel</surname>
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            </name>
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              <surname>Antke</surname>
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  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Case Report</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Labeled stem cells transplantation to the myocardium of a patient with chagas' disease</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>Stem cell transplantation is a new therapy applied to produce cardiac regeneration through differentiation or increase of heart myocytes or neovascular proliferation in patients in the end stage of congestive heart failure secondary to dilated cardiomyopathy&#185;, but the results are still unknown2,3.</p>
      </abstract>
    </front-stub>
    <body>
      <p>
        <bold>CASE REPORT</bold>
      </p>
      <p>Labeled stem cells transplantation to the myocardium of a patient with chagas' disease</p>
      <p>
        <bold>Jos&#233; Luiz Balthazar Jacob; Fernando Vilela Salis; Milton A. Ruiz; Oswaldo Tadeu Greco</bold>
      </p>
      <p> Instituto de Mol&#233;stias Cardiovasculares (IMC) de S&#227;o Jos&#233; do Rio Preto - S&#227;o Jos&#233; do Rio Preto, SP - Brazil</p>
      <p>
        <xref ref-type="corresp" rid="end-body2">Mailing Address</xref>
      </p>
      <p>
        <bold>SUMMARY</bold>
      </p>
      <p>Stem cell transplantation is a new therapy applied to produce cardiac regeneration through differentiation or increase of heart myocytes or neovascular proliferation in patients in the end stage of congestive heart failure secondary to dilated cardiomyopathy<sup>1</sup>, but the results are still unknown<sup>2,3</sup>.</p>
      <p><bold>Key words:</bold> Stem cell transplantation; Chagas' cardiomyopathy; Chagas' disease.</p>
      <p>
        <bold>Case Report</bold>
      </p>
      <p>A 50-year old male individual with refractory heart failure secondary to dilated cardiomyopathy due to Chagas' disease was referred to our Institute that is authorized by the Brazilian Health Ministry to employ stem cell therapy for dilated cardiomyopathy, Chagas' disease and acute myocardial infarction. </p>
      <p>The myocardial perfusion study with 99 mTc SESTAMIBI showed large areas with low uptake in the anterior, apical and septal walls of the left ventricle (<xref ref-type="fig" rid="fig01-body2">Fig. 1</xref>). Cardiac catheterization revealed severe left ventricular dysfunction (ejection fraction = 15.3%) and normal coronary arteries. Despite the optimization of medication, the clinical response remained poor. The patient was informed about the potential risks and benefits of the treatment with stem cell transplantation and signed the Term of Authorized Consent.</p>
      <fig id="fig01-body2">
        <graphic xlink:href="1678-4170-abc-89-02-0e10-00014-gf01-en.jpg"/></fig>
      <p>After the approval of the Research Ethics Committee, the patient underwent stem cell transplantation. </p>
      <p>The patient received epidural anesthesia, and bone marrow cells were obtained by means of punctures in the iliac crest. Twenty milliliters of suspension of mononuclear cells were obtained employing the technique described in the literature<sup>1</sup>. Three milliliters of the suspension were labeled with 99mTc HMPAO. The mononuclear cell suspension was slowly injected (1 ml/minute) into the coronary arteries. Fifty per cent of the suspension was injected into the anterior descending artery, 25% into the left circumflex artery and 25% into the right coronary artery. The 99 mTc HMPAO-labeled cells were injected only into the anterior descending artery. New scintigraphic studies were performed 2 hours and 6 hours after the procedure, respectively.</p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>In patients for whom stem cell transplantation is indicated for the treatment of end stage dilated cardiomyopathy, if the coronary arteries are normal, the selective infusion of the mononuclear cell suspension into the anterior descending artery, the left circumflex artery and the right coronary artery will be our preferred technique. The infusion of the suspension is always made in the distal end of the proximal third of coronary arteries, after proof of absence of retrograde flow is obtained by making a previous injection of contrast medium through the infusion catheter. </p>
      <p>There were doubts, however, whether the cells were retained by the cardiac muscle. This is the reason why the infusion of 99 mTc HMPAO-labeled mononuclear cells was performed using the intracoronary technique previously described.</p>
      <p>Myocardial perfusion studies were repeated to analyze the same axes, 2 and 6 hours, respectively, after the transplantation of labeled mononuclear cells through the intracoronary route and revealed their uptake and retention in areas that had not uptaken SESTAMIBI before (<xref ref-type="fig" rid="fig01-body2">Fig. 1</xref>). The whole-body scintigraphic image showed that the remaining mononuclear cells were uptaken mainly by the liver and spleen (<xref ref-type="fig" rid="fig02-body2">Fig. 2</xref>).</p>
      <fig id="fig02-body2">
        <graphic xlink:href="1678-4170-abc-89-02-0e10-00014-gf02-en.jpg"/></fig>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p>The case reported shows that after the infusion of mononuclear cells through the intracoronary technique, a significant amount of these cells is attracted to areas of the myocardium that had no uptake previously and is retained by these areas (probably in the fibrotic myocardium).</p>
      <p>To our knowledge, this is the first report on these findings in Chagas'disease in the literature.</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 graduation program.</p>
      <p>
        <bold>References</bold>
      </p>
      <p>
        <fn id="end-body2" fn-type="corresp">
          <p>Mailing Address:</p>
          <p> Jos&#233; Luiz Balthazar Jacob</p>
          <p> Rua Castelo D'Agua, 3030 - 15015-210 - S&#227;o Jos&#233; do Rio Preto, SP, Brazil</p>
          <p> E-mail: </p>
          <p>
            <email xlink:href="jljacob@cardiol.br">jljacob@cardiol.br</email>
          </p>
        </fn>
      </p>
      <p> Manuscript received November 24, 2006; revised manuscript received March 1st, 2007; accepted April 3, 2007</p>
    </body>
  </sub-article>
</article>
