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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.0" specific-use="sps-1.1" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <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>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">x5rYHmpBHJp85Ws6y99kQ9m</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2015002100188</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2015005050041</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20150041</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Review Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Nobel Prizes: Contributions to Cardiology</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Mesquita</surname>
            <given-names>Evandro Tinoco</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Marchese</surname>
            <given-names>Luana de Decco</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Dias</surname>
            <given-names>Danielle Warol</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Barbeito</surname>
            <given-names>Andressa Brasil</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gomes</surname>
            <given-names>Jonathan Costa</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Muradas</surname>
            <given-names>Maria Clara Soares</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lanzieri</surname>
            <given-names>Pedro Gemal</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gismondi</surname>
            <given-names>Ronaldo Altenburg</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
          <xref ref-type="corresp" rid="c01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <label>1</label>
        <institution content-type="orgname">Universidade Federal Fluminense</institution>
        <addr-line>
          <named-content content-type="city">Niter&#243;i</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Federal Fluminense, Niter&#243;i, RJ &#8211; Brazil</institution>
        <institution content-type="normalized">Universidade Federal Fluminense</institution>
      </aff>
      <author-notes>
        <corresp id="c01">Mailing Address: Ronaldo Altenburg Odebrecht Curi Gismondi, Universidade Federal Fluminense. Rua Ministro Ot&#225;vio Kelly, 185/701, Icara&#237;. Postal Code 24220-300, Niter&#243;i, RJ &#8211; Brazil E-mail: <email>ronaldo@floralia.com.br</email>, <email>ronaldogismondi@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research:Mesquita ET, Marchese LD, Gismondi RA. Acquisition of data: Marchese LD, Dias DW, Barbeito AB, Gomes JC, Muradas MCS, Gismondi RA. Analysis and interpretation of the data: Mesquita ET, Marchese LD, Gismondi RA. Writing of the manuscript:Mesquita ET, Marchese LD, Dias DW, Barbeito AB, Gomes JC, Muradas MCS, Lanzieri PG, Gismondi RA. Critical revision of the manuscript for intellectual content: Mesquita ET, Marchese LD, Gismondi RA.</p>
        </fn>
        <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>
      <pub-date pub-type="epub">
        <day>05</day>
        <month>05</month>
        <year>2015</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>08</month>
        <year>2015</year>
      </pub-date>
      <volume>105</volume>
      <issue>2</issue>
      <fpage>188</fpage>
      <lpage>196</lpage>
      <history>
        <date date-type="received">
          <day>22</day>
          <month>11</month>
          <year>2014</year>
        </date>
        <date date-type="rev-recd">
          <day>09</day>
          <month>02</month>
          <year>2015</year>
        </date>
        <date date-type="accepted">
          <day>11</day>
          <month>02</month>
          <year>2015</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/">
          <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>
        <p>The Nobel Prize was created by Alfred Nobel. The first prize was awarded in 1901 and Emil Adolf von Behring was the first laureate in medicine due to his research in diphtheria serum. Regarding cardiology, Nobel Prize&#8217;s history permits a global comprehension of progress in pathophysiology, diagnosis and therapeutics of various cardiac diseases in last 120 years. The objective of this study was to review the major scientific discoveries contemplated by Nobel Prizes that contributed to cardiology. In addition, we also hypothesized why Carlos Chagas, one of our most important scientists, did not win the prize in two occasions. We carried out a non-systematic review of Nobel Prize winners, selecting the main studies relevant to heart diseaseamong the laureates. In the period between 1901 and 2013, 204 researches and 104 prizes were awarded in Nobel Prize, of which 16 (15%) studies were important for cardiovascular area. There were 33 (16%) laureates, and two (6%) were women. Fourteen (42%) were American, 15 (45%) Europeans and four (13%) were from other countries. There was only one winner born in Brazil, Peter Medawar, whose career was all in England. Reviewing the history of the Nobel Prize in physiology or medicine area made possible to identify which researchers and studies had contributed to advances in the diagnosis, prevention and treatment of cardiovascular diseases. Most winners were North Americans and Europeans, and male.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Cardiology</kwd>
        <kwd>Nobel Prize</kwd>
        <kwd>History</kwd>
        <kwd>Cardiovascular Diseases / trends</kwd>
      </kwd-group>
      <counts>
        <fig-count count="6"/>
        <table-count count="2"/>
        <equation-count count="0"/>
        <ref-count count="45"/>
        <page-count count="9"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>The Nobel Prize was created by Alfred Nobel (1833-1896) (<xref ref-type="fig" rid="f01">Figure 1</xref>)<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B02">2</xref>. In his will, the Swedish researcher determined the creation of a foundation that would carry his name, of which main objective would be to reward every year, individuals that provided outstanding contributions to mankind in the areas of Peace/Diplomacy, Literature, Chemistry, Physics and Physiology/Medicine. The first prizes were awarded in 1901 and the first winner in Medicine was Emil Adolf von Behring, for his work with diphtheria serum<xref ref-type="bibr" rid="B01">1</xref>. Since that date, there have been 876 Nobel Prize winners, of which 104 awards and 204 researchers in the area of Medicine or Physiology<xref ref-type="bibr" rid="B01">1</xref>.</p>
      <p>The objective of the present study was to review the major scientific discoveries that received the Nobel Prize and directly or indirectly contributed to advances in physiopathology, diagnosis and treatment of cardiovascular diseases.</p>
      <fig id="f01">
        <label>Figure 1</label>
        <caption>
          <title>Nobel Prize Logo.</title>
        </caption>
        <attrib>Source: <ext-link ext-link-type="uri" xlink:href="http://en.wikipedia.org/wiki/Nobel_Prize">http://en.wikipedia.org/wiki/Nobel_Prize</ext-link>
				</attrib>
        <graphic xlink:href="1678-4170-abc-105-02-0188-50041-gf01.jpg"/></fig>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>We performed a systematic search of the main non Nobel Prize winners from 1901 to 2013. The winners list was obtained from the Nobel Prize site<xref ref-type="bibr" rid="B03">3</xref> and, subsequently, information about the authors and their research were obtained from the Medline/PubMed database. Moreover, due to the specific nature of the research involving historical and bibliographical data, the Google search engine was utilized, using as descriptors the names of the researchers awarded the Nobel Prize. The results are displayed in ascending chronological order.</p>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>A brief history of the Nobel Prize</title>
        <p>For many historians, the interest of Alfred Nobel in medicine derived from a poor health<xref ref-type="bibr" rid="B02">2</xref>. There are reports of dyspepsia, headaches and bouts of depression. In adulthood, he would have suffered from coronary artery disease, with frequent episodes of angina. His doctors recommended the use of nitroglycerin, a substance Nobel manipulated in the explosives industry, but he would have refused. In later life he had a stroke and had to live with motor sequelae. Skeptical and suspicious, Nobel expressed in his will the wish that after his death, his veins were "open" and the signs of death confirmed by "competent doctors," before the body was sent to be cremated<xref ref-type="bibr" rid="B01">1</xref>.</p>
        <p>Nobel&#8217;s choice of the Karolinska Institute in his will surprised many scientists. This institute was created in 1810 from the merging of a Medical School and a small surgical center where barbers were trained to perform amputations. For years it did not have the status of School of Medicine and depended on a contract with the University of Uppsala, in Sweden, for the training of its professionals<xref ref-type="bibr" rid="B01">1</xref>. Currently, the institute is one of the leading Assistance Medicine and Research centers in Europe. Five Nobel Prize winners over the last 120 years, came from this institute<xref ref-type="bibr" rid="B01">1</xref>.</p>
      </sec>
      <sec>
        <title>The Nobel Prize and Cardiology</title>
        <p>In the area of cardiology, specifically regarding heart failure (HF), knowledge of the history of the Nobel Prize helps to understand important diagnostic and therapeutic advances made in the last 120 years (<xref ref-type="table" rid="t01">Chart 1</xref>). The first laureate in this area was Alexis Carrel, for his discoveries related to blood vessel suture, an important step in the further development of cardiac surgery<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B03">3</xref>. Only one Brazilian, who lived in England, was awarded. His name is Peter Medawar and he has carried out researches in the immunosuppression area, with future applicability in renal and cardiac transplant<xref ref-type="bibr" rid="B04">4</xref><sup>,</sup><xref ref-type="bibr" rid="B05">5</xref>.</p>
        <table-wrap id="t01">
          <label>Chart 1</label>
          <caption>
            <title>Main scientific discoveries that received the Nobel Prize in Physiology or Medicine related to the Cardiology area</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>Year</bold>
                </th>
                <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>Author</bold>
                </th>
                <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>Prize</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>1912</td>
                <td align="center">Alexis Carrel</td>
                <td align="center">Work on vascular suture and transplant of blood vessels and organs</td>
              </tr>
              <tr>
                <td>1924</td>
                <td align="center">Willem Einthoven</td>
                <td align="center">Electrocardiogram</td>
              </tr>
              <tr>
                <td>1953</td>
                <td align="center">Hans Adolf Krebs</td>
                <td align="center">Citric acid cycle (Krebs cycle)</td>
              </tr>
              <tr>
                <td>1956</td>
                <td align="center">Werner Forssmann, Andre Cournard and Dickinson W. Richards</td>
                <td align="center">Cardiac catheterization</td>
              </tr>
              <tr>
                <td>1960</td>
                <td align="center">Frank Burnet and Peter Medawar</td>
                <td align="center">Discovery of the immunological tolerance mechanism</td>
              </tr>
              <tr>
                <td>1964</td>
                <td align="center">Konrad Bloch and Feodor Lynen</td>
                <td align="center">Understanding of cholesterol metabolism</td>
              </tr>
              <tr>
                <td>1979</td>
                <td align="center">Allan Cormack and Godfrey Hounsfield</td>
                <td align="center">Computed tomography techniques</td>
              </tr>
              <tr>
                <td>1982</td>
                <td align="center">Bengt Samuelsson, Sune Bergstr&#246;m and John Vane</td>
                <td align="center">"Discovery" of the angiotensin-converting enzyme inhibitors</td>
              </tr>
              <tr>
                <td>1985</td>
                <td align="center">Michael Brown and Joseph Goldstein</td>
                <td align="center">Discovery of LDL-cholesterol receptors</td>
              </tr>
              <tr>
                <td>1988</td>
                <td align="center">James Black, Gertrude Elion and George Hitchings</td>
                <td align="center">Development of beta-blockers</td>
              </tr>
              <tr>
                <td>1990</td>
                <td align="center">Joseph Edward Murray and Edward Thomas</td>
                <td align="center">Development of organ and tissue transplant</td>
              </tr>
              <tr>
                <td>1998</td>
                <td align="center">Robert Furchgott, Ferid Murad and Louis Ignarro</td>
                <td align="center">Discoveries about nitric oxide</td>
              </tr>
              <tr>
                <td>2003</td>
                <td align="center">Paul Lauterbur and Peter Mansfield</td>
                <td align="center">Magnetic Resonance</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn>
              <p>LDL: low-density lipoprotein.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Although Carlos Chagas researched and discovered the etiological agent, the vector, the mode of transmission and clinical forms of trypanosomiasis, a unique feat in the history of world&#8217;s science, he was a candidate for the Nobel a few times, but was unsuccessful. There are hypotheses that attempt to explain why a genuinely Brazilian contribution in the field of cardiology has not been contemplated with the Nobel prize<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref>.</p>
      </sec>
      <sec>
        <title>Major studies important for Cardiology that were awarded the Nobel Prize</title>
        <sec>
          <title>Alexis Carrel &#8211; 1912: blood vessel suture</title>
          <p>Alexis Carrel, was born in Sainte-Foy-l&#232;s-Lyon, France, graduated in Medicine from the School of Medicine of Lyon in 1893 and completed his doctorate in 1900, with a research on blood vessel sutures. He taught Anatomy and Surgery at the University of Lyons and moved to the United States in 1904, where he worked at the University of Chicago. Later, he joined the Rockefeller Institute for Medical Research in New York, where he performed most of the experiments that led to the Nobel Prize in Physiology or Medicine in 1912. He served the medical corps of the French Army during World War I (1914 -1918), where he successfully used the Carrel-Dakin method of constant irrigation of wounds with antiseptic solution, which decreased cases of death and amputations<xref ref-type="bibr" rid="B01">1</xref><sup>-</sup><xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B08">8</xref>.</p>
          <p>His early work was on surgical techniques in blood vessels and arteriovenous anastomoses. After 1908, he developed methods for organ cryopreservation and transplantation<xref ref-type="bibr" rid="B01">1</xref><sup>-</sup><xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B08">8</xref>. In 1935, he created a system for sterile oxygen supply and preservation of organs removed from the body. He also cooperated with other researchers for the development of cardiac valvotomy surgery and sarcoma cell culture. He published the books &#8220;The culture of organs&#8221; and &#8220;Treatment of infected wounds&#8221;<xref ref-type="bibr" rid="B01">1</xref><sup>-</sup><xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B08">8</xref>. The suture of blood vessels was essential for the development of vascular surgery in later years.</p>
        </sec>
        <sec>
          <title>Willem Einthoven &#8211; 1924: The Electrocardiogram</title>
          <p>Willem Einthoven was born on May 21, 1860 on the island of Java, now Indonesia, and moved to the Netherlands in 1870, where he graduated from Medical School at the University of Utrecht, one of the oldest and most traditional medical schools in Europe. He was a physiologist and in the early 20<sup>th</sup> century, he published several papers on the use of the galvanometer in the recording of the human electrocardiogram (ECG), which served as the basis for the current devices. The original equipment weighed more than 270 kg and was operated by several people in his laboratory. He described the P, QRS and T waves, as well as and their alterations in several diseases, especially in valvular heart disease. Showing great wisdom, he wrote after his initial research, &#8220;the electrocardiogram should not be used, at least exclusively, to diagnose valvular alterations, because the ECG is the expression of the heart muscle contraction and changes only to the extent that a valvular function failure has influence on such contraction&#8221;<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B02">2</xref><sup>,</sup><xref ref-type="bibr" rid="B09">9</xref>.</p>
          <p>In addition to the ECG, Einthoven played an important role in the development of the phonocardiogram<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B02">2</xref><sup>,</sup><xref ref-type="bibr" rid="B09">9</xref>. This device, now a museum piece in many medical schools, was crucial in the supplementary examination to medical workup. Before the invention of echocardiography, many valvular heart disease diagnoses were attained by auscultation and the phonocardiogram. The valvular diseases were, until the early 20<sup>th</sup> century, one of the most important causes of heart failure, particularly those of rheumatic origin.</p>
          <p>Hans Adolf Krebs was born on August 25, 1900, in Hildeshiem, northern Germany<xref ref-type="bibr" rid="B10">10</xref>. He served as a military in the German army in World War I. Although he graduated in Medicine, he had to go into exile and left Germany in the 1930s, because of his Jewish descent. He chose to live in England, where he developed his research related to cell physiology. He described, together with other researchers, the urea cycle, the citric acid cycle, and especially, cellular respiration, which produces adenosine triphosphate (ATP) from glucose and oxygen<xref ref-type="bibr" rid="B10">10</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref>. In his honor, this sequence of biochemical reactions is known as "Krebs cycle".</p>
          <p>It has long been known that mitochondrial diseases are a group of diseases related to neuromuscular dysfunction and cardiomyopathy<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref>. Moreover, in cardiology, the study of the mitochondrial function in the myocyte is a new research frontier, which some have called "mitochondrial bioenergetics"<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref>. One of the key areas is HF, due to the role of aerobic metabolism in myocardial performance. Drugs are being developed that act on mitochondrial pathways, correcting occasional dysfunctions, and it is expected that they can improve myocardial function<xref ref-type="bibr" rid="B14">14</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref>.</p>
          <p>The history of cardiac catheterization started in 1711, based on the works of Stephen Hales, who inserted tubes in both ventricles of a horse<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B16">16</xref><sup>-</sup><xref ref-type="bibr" rid="B19">19</xref>. In the 19<sup>th</sup> century, cardiac catheterization continued with the work of Claude Bernard, the father of modern physiology; it became more sophisticated with the skills of Chauveau and Marey; and started to be applied in the human heart thanks to the self&#8209;confidence of Forssmann in 1929, becoming therapeutic in 1966<xref ref-type="bibr" rid="B20">20</xref>. According to Cournnand<xref ref-type="bibr" rid="B17">17</xref>, cardiac catheterization can be considered the "key that opened the lock to reveal the secrets of the heart." Due to the advancement of the technique proposed by the laureates, currently the hemodynamic study has applicability in the diagnosis, treatment and monitoring of cardiovascular disease - including Coronary Artery Disease (CAD) and HF.</p>
          <p>The Nobel Prize in Physiology or Medicine in 1956 was awarded to three researchers, due to their researches on catheterization that revolutionized the studies on heart disease<xref ref-type="bibr" rid="B01">1</xref>. They would not accept with the scarcity of semiotic methods, of which provided diagnoses were rebuffed by autopsies, which served as motivation to initiate their studies<xref ref-type="bibr" rid="B01">1</xref>.</p>
          <p>Werner Forssmann was a German physician, born in Berlin, who developed the hypothesis that a catheter could be inserted through blood vessels to the heart, aiming to injecting medications, perform contrast studies and measure chamber pressures. In order to test his hypothesis, he performed the first human catheterization in himself, guiding a catheter into his left atrium with the aid of a fluoroscopy device<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B16">16</xref><sup>-</sup><xref ref-type="bibr" rid="B19">19</xref>.</p>
          <p>Andre Cournard, born in Paris, France and Dickinson Richards, from Orange, United States, were physicians who worked in the development of the cardiac catheterization technique, with emphasis on pulmonary diseases and patterns of circulatory shock. They described the shock patterns, particularly cardiogenic and hemorrhagic (trauma) and analyzed the hemodynamic changes with treatment, either by fluid replacement or drug infusion<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B16">16</xref><sup>-</sup><xref ref-type="bibr" rid="B19">19</xref>.</p>
        </sec>
        <sec>
          <title>Frank Macfarlane Burnet and Peter Brian Medawar &#8211; 1960: immunological tolerance</title>
          <p>Sir Frank Macfarlane Burnet was born in Australia and was the son of Scottish parents. He obtained a degree in Medicine in his native country and post-graduated in England. He specialized in the virology area, with important research related to influenza virus and herpes simplex. He played a key role in virus isolation from human tissue, and the first attempts to develop a vaccine for influenza. After World War II, he also developed researches related to the immune system, especially autoimmune mechanisms and immunological tolerance<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B02">2</xref><sup>,</sup><xref ref-type="bibr" rid="B21">21</xref><sup>-</sup><xref ref-type="bibr" rid="B23">23</xref>.</p>
          <p>Peter Brian Medawar (<xref ref-type="fig" rid="f02">Figure 2</xref>) was born in Petropolis (RJ), and had an English mother and Lebanese father. The family moved to England when he was only 14, where he developed his studies and career. Differences with the Brazilian government, which required his mandatory military service, made him give up his Brazilian nationality. He majored in zoology at Oxford and began transplantation research during World War II. The main objectives were skin grafts in burned skin areas. His studies led to the theory of acquired immunological tolerance, the basis for the development of solid organ transplants in the future<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B02">2</xref><sup>,</sup><xref ref-type="bibr" rid="B04">4</xref><sup>,</sup><xref ref-type="bibr" rid="B05">5</xref>. The connection made between his research and Cardiology was the applicability of his results on immunological tolerance for the future development of heart transplantation.</p>
          <fig id="f02">
            <label>Figure 2</label>
            <caption>
              <title>Peter Medawar&#8217;s picture.</title>
            </caption>
            <attrib>Source: <ext-link ext-link-type="uri" xlink:href="http://www.nobelprize.org/nobel_prizes/medicine/laureates/1960/medawar-facts.html">http://www.nobelprize.org/nobel_prizes/medicine/laureates/1960/medawar-facts.html</ext-link>
						</attrib>
            <graphic xlink:href="1678-4170-abc-105-02-0188-50041-gf02.jpg"/></fig>
        </sec>
        <sec>
          <title>Konrad Bloch and Feodor Lynen &#8211; 1964: cholesterol metabolism</title>
          <p>The Nobel Prize in Physiology or Medicine of 1964 was awarded jointly to two German chemists, Konrad Bloch and Feodor Lynen. Bloch was born on January 21, 1912, in Neisse (now Nysa), formerly part of Germany and currently in Poland. He graduated in chemical engineering in 1934 in Munich. In 1936, due to the persecution of Jews by the Nazis, Bloch immigrated to the United States and joined the Department of Biochemistry at Columbia University, where he developed the research that led him to be awarded the Nobel Prize.</p>
          <p>Feodor Lynen was born on April 6, 1911, in Munich, Germany, where he graduated in chemistry. He developed his entire career in Germany, living there even during the world wars<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref>.</p>
          <p>Even without performing a real joint work, both researchers carried out important discoveries in their universities on the cholesterol regulation mechanism and the fatty acid metabolism<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref>. Starting from the idea that the acetic acid, with slow reaction in the chemical essays, had to show a more rapid and spontaneous reaction in the body, the concept of activated acetic acid was formulated, in which, in addition to adenyl-phosphoric acid as an energy source, also included coenzyme A. They were able to determine not only the structure of cholesterol, as well as the participation of coenzyme A in the oxidation of the fatty acids<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref>. Years later, these discoveries were crucial to demonstrate the importance of cholesterol in atherosclerosis and, more importantly, helped the development of statins, the major class of drugs for treatment of hypercholesterolemia and atherosclerotic disease.</p>
        </sec>
        <sec>
          <title>Allan M. Cormack and Godfrey Hounsfield - 1979: computed tomography</title>
          <p>Allan Cormack was a South African biochemist and nuclear physicist born in Johannesburg (South Africa), who became a naturalized American in 1966. He is considered one of the inventors of computed tomography and shared the Nobel Prize in Physiology or Medicine with British professor Godfrey Hounsfield. Cormack performed his research in radiology initially at the University of Cape Town until he immigrated to the United States, where he worked at Harvard and Tufts University. There, he tested a mathematical model based on the X radiation, essential to the development of computed axial tomography<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B25">25</xref>.</p>
          <p>Sir Godfrey Hounsfield was an electrical engineer who had the position of "inventor" at the Central Research Laboratories in London. He started his career working on a radar project as a weapon of war and designed the first British transistorized computer in 1958, "EMIDEC 1100". Based on the mathematical calculations of radiation developed by Cormack, he developed Computed Tomography (CT) &#8211; so that the first machine to "scan" the brain was marketed by EMI. Three years later, he developed the first CT for the entire body. He continued to make improvements in CT and received numerous awards and honors, in addition to the Nobel prize, with his latest award being the title of Knight of the Queen of England - Sir, in 1981<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B25">25</xref>. CT developed further in the following years and now has several applications in cardiology, for instance, determination of the coronary anatomy and the calcium score, and in the assessment of pulmonary thromboembolism.</p>
        </sec>
        <sec>
          <title>Bengt Samuelsso, Sune Bergstr&#246;m and John Vane &#8211; 1982: prostaglandin function and development of angiotensinconverting enzyme inhibitors</title>
          <p>Bengt Ingemar Samuelsso was a Swedish biochemist born in 1934 in Halmstad, a researcher at the Karolinska Institute in Sweden, and Nobel Prize laureate in Physiology or Medicine with his institute colleague and also Swedish biochemist Sune K. Bergstr&#246;m, and with the English chemist and pharmacologist John Robert Vane <xref ref-type="bibr" rid="B01">1</xref>. His research involved prostaglandin function, purification, determination of their chemical structure and identification of their mechanism of formation from unsaturated fatty acids<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B26">26</xref><sup>,</sup><xref ref-type="bibr" rid="B27">27</xref>. This information allowed the proposition of acetylsalicylic acid mechanism of action, practically indispensable treatment in coronary heart disease.</p>
          <p>In addition to the research on prostaglandins, John Vane is also considered one of the "discoverers" of Angiotensin-Converting Enzyme inhibitors (ACE inhibitors)<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B26">26</xref><sup>,</sup><xref ref-type="bibr" rid="B27">27</xref>. During the 1960s and 1970s, and with the participation of Brazilian Sergio Ferreira, Vane and his colleagues demonstrated key steps in the synthesis of angiotensin and bradykinin, which, in 1982, culminated in the launching of the first ACEI, captopril<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B26">26</xref><sup>,</sup><xref ref-type="bibr" rid="B27">27</xref>. This class of drugs has a vital role in the treatment of hypertension, heart failure and coronary artery disease.</p>
        </sec>
        <sec>
          <title>Michael Brown e Joseph Goldstein &#8211; 1985: LDL-cholesterol receptors</title>
          <p>Joseph L. Goldstein was born on April 18, 1940 in Sumter, South Carolina, in the United States. He initially graduated in chemistry from Washington and Lee University and subsequently, obtained his medical degree at UT Southwestern Medical Center Dallas. He was a resident at Massachusetts General Hospital, where he met Michael S. Brown, who later would become his collaborator and together, they won the Nobel Prize<xref ref-type="bibr" rid="B03">3</xref>. During the two following years, he worked at the National Heart, Lung, and Blood Institute of the United States, which contributed to increase his skills and taste for scientific experimentation from the perspective of molecular biology in human disease<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B28">28</xref><sup>-</sup><xref ref-type="bibr" rid="B30">30</xref>.</p>
          <p>Michael Stuart Brown was born on April 13, 1941, in Brooklyn, New York. Similarly to Goldstein, he first obtained a degree in chemistry and only then in Medicine. He also worked at the National Heart, Lung, and Blood Institute of the US, but in the area of gastroenterology and hereditary diseases. In biochemistry laboratory, he learned enzymatic manipulation techniques, among which, an enzyme that could be related to familial hypercholesterolemia<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B28">28</xref><sup>-</sup><xref ref-type="bibr" rid="B30">30</xref>.</p>
          <p>Goldstein and Brown were awarded the Nobel Prize for scientific research in which they identified receptors on the surface of cells that mediate the uptake of Low-Density Lipoprotein (LDL) circulating in the bloodstream. Furthermore, they found that severe familial hypercholesterolemia is closely related to these receptors, as with the decrease in the number of membrane receptors, there is a lower uptake of circulating cholesterol in the form of LDL, thus increasing levels of the substance in the bloodstream from<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B28">28</xref><sup>-</sup><xref ref-type="bibr" rid="B30">30</xref>. In this example, once again, one can observe the close association between high cholesterol levels, atherosclerosis, and ischemic heart disease.</p>
        </sec>
        <sec>
          <title>James Black, Gertrude Elion and George Hitchings &#8211; 1988: beta-blockers</title>
          <p>James W. Black, from Uddington, Scotland, studied medicine at the University of St. Andrews. In 1948, he started an investigation on cardiac adrenergic alpha and beta receptors, resulting in the synthesis of propranolol, the prototype of beta-blockers, essential medications for the treatment of heart failure and coronary artery disease. Later, in 1976, he concluded the synthesis of cimetidine, histamine H2-receptor antagonist, used in peptic disease treatments. Together with James W. Black, researchers Gertrude B. Elion (New York, United States) and George H. Hitchings (Hoquiam, United States) were also awarded the Nobel Prize of Medicine, for the development of drugs used in chemotherapy, antibiotics and antivirals<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B31">31</xref>.</p>
        </sec>
        <sec>
          <title>Joseph Edward Murray and Edward Thomas &#8211; 1990: organ transplantation</title>
          <p>Joseph Murray was born on April 1<sup>st</sup>, 1919 in the city of Milford, State of Massachusetts (United States) and died in 2012 due to a stroke. He graduated from Harvard medical school and specialized in plastic surgery. He served in the US military and had a very important role in the care of wounded soldiers in World War II. When caring for burned patients, he observed that many patients responded well to donor skin grafts and decided to develop a research related to organ transplantation. On December 23, 1954, he was part of the team that made the first renal transplantation and, some years later, the first transplantation using a cadaveric source. Over the years, he participated in studies on immunosuppressive drugs such as azathioprine, aimed at reducing graft rejection<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B32">32</xref>.</p>
          <p>Edward Donall Thomas was born on March 20, 1920, in the city of Mart, State of Texas (United States), and also died in 2012. He graduated from medical school at Harvard and, early in his career, he devoted himself to laboratory studies related to bone marrow transplantation. Together with Joseph Edward Murray, he received the Nobel Prize in Physiology or Medicine as his studies helped to develop the transplantation of organs and tissues. In the field of HF, heart transplantation was indicated for patients that remained very symptomatic despite optimal medical treatment, which was performed for the first time in history in South Africa by Dr. Christiaan Barnard<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B32">32</xref>.</p>
        </sec>
        <sec>
          <title>Robert F. Furchgott, Ferid Murad and Louis J. Ignarro &#8211; 1998: nitric oxide</title>
          <p>The Nobel Prize in Physiology or Medicine in 1998 was awarded jointly to Robert F. Furchgott (Charleston, United States), Louis J. Ignarro (New York, United States) and Ferid Murad (Whiting, United States) due to their findings on Nitric Oxide (NO) as a signaling molecule in the cardiovascular system<xref ref-type="bibr" rid="B01">1</xref>. NO is a soluble gas naturally found in the human body, which acts on the signaling of several biological processes.</p>
          <p>The synthesis of NO occurs through the action of an enzyme called NO synthase (NOS) from L-arginine and L-citrulline amino acids, requiring for this enzymatic reaction, the presence of two cofactors, oxygen and Nicotinamide Adenine Dinucleotide Phosphate (NADPH). There are three types of NOS, two of them called constitutive and calcium-dependent NOS (cNOS), which are the endothelial and neuronal forms that synthesize NO in normal conditions and the calcium-independent form (iNOS), which is not expressed or is in a much lesser amount under physiological conditions. NO plays an important role in endothelial homeostasis, contributing with its vasodilating and anticoagulant properties. There is evidence that a decreased NO production is an important factor in ischemic events in patients with coronary artery disease and other suggesting that NO can exert antiatherosclerotic actions. Furthermore, the nitrates, the most widely used drugs in coronary artery disease and heart failure, act by indirectly increasing NO bioavailability<xref ref-type="bibr" rid="B33">33</xref><sup>-</sup><xref ref-type="bibr" rid="B36">36</xref>.</p>
        </sec>
        <sec>
          <title>Paul C. Lauterbur and Peter Mansfield &#8211; 2003: magnetic resonance</title>
          <p>Paul Lauterbur was born on May 6, 1929 in the United States, having obtained his PhD in Chemistry at the University of Pittsburgh in Pennsylvania (United States). Throughout his career has received numerous awards for his work related to magnetic resonance, including the gold medal of the Society of Magnetic Resonance in Medicine in 1982, the European Prize of Magnetic Resonance in 1986, the International Society for Magnetic Resonance in Medicine Award in 1992, the gold medal of the European Congress of Radiology in 1999, the NAS Award for Chemistry in Service to Society in 2001 and the Nobel Prize in Physiology or Medicine in 2003 together with Englishman Sir Peter Mansfield<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B37">37</xref><sup>-</sup><xref ref-type="bibr" rid="B39">39</xref>.</p>
          <p>Peter Mansfield was born on October 9, 1933 in London and a received his Ph.D. in physics in his hometown in 1962. In the course of his career as an investigator he received several awards, including the Gold Medal of the Society for Magnetic Resonance in Medicine in 1983, the European Prize of Magnetic Resonance in 1988, the title of Sir of the British Crown in 1993, the Gold Medal of the European Congress of Radiology and the European Association of Radiology in 1995 and the Nobel Prize for Physiology and Medicine, for his discoveries related to nuclear magnetic resonance imaging in 2003<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B37">37</xref><sup>-</sup><xref ref-type="bibr" rid="B39">39</xref>.</p>
          <p>Based on the initial findings of Lauterbur and Mansfield, MRI has developed and now has wide application in cardiology. It is considered, for instance, the gold standard in non-invasive myocardial and heart function assessment.</p>
        </sec>
      </sec>
      <sec>
        <title>Special Considerations</title>
        <sec>
          <title>Carlos Chagas &#8211; 1911: an unjustly overlooked scientist in relation to the Nobel Prize</title>
          <p>Carlos Chagas (<xref ref-type="fig" rid="f03">Figure 3</xref>) was the first researcher in the world's scientific history to describe the complete cycle of a disease, currently known as Chagas disease<xref ref-type="bibr" rid="B40">40</xref>. His research with <italic>Trypanosoma cruzi</italic> started between the years 1907 and 1909, when he was sent to the countryside of the state of Minas Gerais to help fight malaria among workers building the Brazilian Central Railway<xref ref-type="bibr" rid="B07">7</xref>. In 1909, he identified the parasite in the blood of a child with "fever, anemia, edema and generalized lymphadenopathy" and later described the life cycle of <italic>T. cruzi</italic><xref ref-type="bibr" rid="B07">7</xref>. Aided by a small team, he changed history as a scientist that inspired a new era of knowledge, as he was able to draw a clinical profile from his own observations.</p>
          <fig id="f03">
            <label>Figure 3</label>
            <caption>
              <title>Carlos Chagas picture. Source: Lagoeiro B, Gemal P. Carlos Chagas. Um homem, uma doen&#231;a, uma hist&#243;ria. Niter&#243;i: Ed. UFF; 2012.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-105-02-0188-50041-gf03.jpg"/></fig>
          <p>Throughout his career, he received honors of national importance, such as public health management positions, as well as international prizes, such as the Schauddinn award in Germany, for the most important discovery of protozoology. For these reasons, he was nominated four times for the Nobel Prize, but none fructified. Researchers and historians have assessed, among other sources, files from Oswaldo Cruz Foundation and the Karolinska Institute to identify the reasons why Carlos Chagas was not awarded the Nobel prize<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref><sup>,</sup><xref ref-type="bibr" rid="B41">41</xref><sup>-</sup><xref ref-type="bibr" rid="B43">43</xref>.</p>
          <p>Bestetti et al.<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref><sup>,</sup><xref ref-type="bibr" rid="B41">41</xref><sup>,</sup><xref ref-type="bibr" rid="B42">42</xref>, in their set of historical publications, solidly based the reasons why Chagas was not a Nobel Prize laureate. These researchers even went to the Swedish institute in person to review the original documents of the time; their research, published in prestigious international journals, are less disseminated than they should be in Brazilian cardiology.</p>
          <p>Gunnar Hedr&#232;n was the board member of the Karolinska Institute who analyzed and issued an opinion on Chagas&#8217; first nomination for the Nobel Prize in 1921<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref>. Although there is no formal written opinion, the analysis of documents from that time suggests that the counselor did not value Chagas&#8217; discovery<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref>. Although now recognized as renowned researcher, Chagas had opponents in South America and Brazil. A group linked to the Bacteriology Institute in Buenos Aires, including a Brazilian member, insisted in the early years of Chagas' discovery, that there was no association between the symptoms reported by Chagas and the presence of <italic>T. cruzi</italic><xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B44">44</xref>. Another group, from the very Oswaldo Cruz Foundation and the School of Medicine of Rio de Janeiro, disagreed with Chagas for political reasons and, on several occasions, questioned the importance of trypanosomiasis<xref ref-type="bibr" rid="B06">6</xref>. Among his opponents were Figueiredo de Vasconcellos, Cardoso Fontes and Plinio Marques<xref ref-type="bibr" rid="B06">6</xref>.</p>
          <p>Chagas also lost prestige among the local population for unpopular measures at the time when he was appointed Director of Public Health, an equivalent post at the time of the "Minister of Health". The mandatory vaccine for smallpox was one of those most criticized measures, being even the reason of a popular revolt<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B42">42</xref>. Finally, the methods used by the then President of the Karolinska Institute, JE Johansson, are criticized. It is suggested that he excessively valued researches related to physiology, rather than those related to clinical medicine<xref ref-type="bibr" rid="B42">42</xref>.</p>
          <p>A new indication and a Nobel award after Chagas&#8217; death are no longer expected. It persists, though, in the light of the centenary of the discovery by Chagas, our pride in a great Brazilian who, with all the honors and merits, made such a contribution to humankind.</p>
        </sec>
        <sec>
          <title>Bernard Lown &#8211; a brilliant clinical cardiologist that received the Peace Nobel Prize of 1985</title>
          <p>Bernard Lown was born on June 7, 1921, in the city of Utena, Lithuania, and moved at age 13 with his family to the USA and settled in the state of Maine, where he became a medical doctor and completed his specialization in cardiology at the current Brigham and Women's hospital in Boston<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B45">45</xref>. Together with engineer Baruch Berkowitz, in 1961, he created the direct current used in the defibrillator, allowing greater safety and efficacy in relation to the then AC defibrillator created by Paul Zoll. Lown also discovered the correct moment of the cardiac cycle in ECG for the electrical discharge in ventricular tachyarrhythmias. This therapy received the name of "cardioversion". The defibrillator designed by Lown and Berkowitz was used as standard therapy in cardiac arrhythmias until the 1980s, when the models with biphasic current were created. He also has researched the use of lidocaine as an antiarrhythmic drug and the importance of serum potassium in digitalis intoxication. Lidocaine, until then, was basically used as a local anesthetic by dentists. In the presence of HF, electrical therapies are essential in preventing sudden death (of which ventricular dysfunction is one of the most important risk factors) and in the treatment of symptomatic arrhythmias, highly prevalent in this group; digoxin is one of the drugs indicated for patients with reduced ejection fraction and symptomatic ones with functional class III or IV<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B45">45</xref>.</p>
          <p>Despite all these contributions to Medicine, his Nobel Prize was won by other merits: a peacekeeper, he created the International Physicians for the Prevention of Nuclear War, in association with the then Soviet citizen Yevgeniy Chazov. His association has also had the participation of Brazilian physicians. He also published two famous books: &#8220;The lost art of healing&#8221; and &#8220;Prescription for survival: a doctor's journey to end nuclear madness&#8221;. He is currently a Professor Emeritus at Harvard University and founder of the Lown Institute, of which mission is described on their website as: &#8220;to help set up a sustainable and compassionate health system, where doctors can serve as healers and lawyers, where patients receive the services they need and are protected from unnecessary treatment and damage, and where financial incentives are removed from clinical decision-making&#8221;<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B45">45</xref>.</p>
        </sec>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>The Nobel Prize aims to reward researchers whose actions and discoveries have contributed exceptionally to the progress and the good of society. Regarding heart failure, the final pathway of several forms of heart disease, 33 researchers in 16 awards performed studies that yielded great contributions to its diagnosis and treatment. Brazil, despite its growing scientific contributions in recent decades, in the fields of Physiology and Medicine, has no "genuinely" Brazilian laureates, despite the contributions of Dr. Peter Medawar and Dr. Carlos Chagas - the latter unjustly not a recipient of this honor.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="supported-by">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>The study is associated with the Post-Graduate Program in Cardiovascular Sciences of Universidade Federal Fluminense.</p>
      </fn>
    </fn-group>
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  <sub-article article-type="translation" id="SA1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo de Revis&#227;o</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Pr&#234;mios Nobel: Contribui&#231;&#245;es para a Cardiologia</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Mesquita</surname>
            <given-names>Evandro Tinoco</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Marchese</surname>
            <given-names>Luana de Decco</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Dias</surname>
            <given-names>Danielle Warol</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Barbeito</surname>
            <given-names>Andressa Brasil</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gomes</surname>
            <given-names>Jonathan Costa</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Muradas</surname>
            <given-names>Maria Clara Soares</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lanzieri</surname>
            <given-names>Pedro Gemal</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gismondi</surname>
            <given-names>Ronaldo Altenburg</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">1</xref>
          <xref ref-type="corresp" rid="c02"/>
        </contrib>
      </contrib-group>
      <aff id="aff02">
        <label>1</label>
        <institution content-type="original">Universidade Federal Fluminense, Niter&#243;i, RJ &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c02"><bold>Correspond&#234;ncia: Ronaldo Altenburg Odebrecht Curi Gismondi</bold>, Universidade Federal Fluminense. Rua Ministro Ot&#225;vio Kelly, 185/701, Icara&#237;. CEP: 24220-300, Niter&#243;i, RJ &#8211; Brasil E-mail: <email>ronaldo@floralia.com.br</email>, <email>ronaldogismondi@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Mesquita ET, Marchese LD, Gismondi RA. Obten&#231;&#227;o de dados: Marchese LD, Dias DW, Barbeito AB, Gomes JC, Muradas MCS, Gismondi RA. An&#225;lise e interpreta&#231;&#227;o dos dados: Mesquita ET, Marchese LD, Gismondi RA. Reda&#231;&#227;o do manuscrito: Mesquita ET, Marchese LD, Dias DW, Barbeito AB, Gomes JC, Muradas MCS, Lanzieri PG, Gismondi RA. Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante:Mesquita ET, Marchese LD, Gismondi RA.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesse</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <p>O Pr&#234;mio Nobel foi criado por Alfred Nobel. Os primeiros pr&#234;mios foram entregues em 1901, e o primeiro ganhador na &#225;rea da medicina foi Emil Adolf von Behring, por seus trabalhos com soro antidift&#233;rico. Na cardiologia, o conhecimento da hist&#243;ria do Pr&#234;mio Nobel ajuda a entender a import&#226;ncia dos avan&#231;os fisiopatol&#243;gicos, diagn&#243;sticos e terap&#234;uticos realizados ao longo dos &#250;ltimos 120 anos. O objetivo do presente estudo foi revisar as principais descobertas cient&#237;ficas contempladas pelo Pr&#234;mio Nobel, que contribu&#237;ram para avan&#231;os no estudo da cardiologia. Al&#233;m disso, apresentamos a hip&#243;tese pela qual Carlos Chagas, um dos nossos mais importantes cientistas, n&#227;o recebeu o Pr&#234;mio Nobel em duas ocasi&#245;es. A partir de uma revis&#227;o n&#227;o sistem&#225;tica sobre os Pr&#234;mios Nobel, foram selecionados, entre os laureados, os principais estudos com relev&#226;ncia para as doen&#231;as card&#237;acas. No per&#237;odo entre 1901 e 2013, 204 pesquisadores, em 104 pr&#234;mios, foram premiados na categoria Medicina ou Fisiologia, dos quais 16 estudos (15%) tiveram import&#226;ncia na &#225;rea da cardiologia. Foram 33 (16%) premiados, sendo apenas duas (6%) mulheres. Em rela&#231;&#227;o ao local de nascimento, 14 (42%) eram norte-americanos, 15 (45%) europeus e quatro (13%) de outros pa&#237;ses. Apenas um laureado nasceu no Brasil: Peter Medawar, cuja carreira se deu toda na Inglaterra. A revis&#227;o da hist&#243;ria do Pr&#234;mio Nobel na &#225;rea de medicina ou fisiologia possibilitou identificar pesquisadores e estudos que contribu&#237;ram para avan&#231;os no diagn&#243;stico, preven&#231;&#227;o e tratamento das doen&#231;as cardiovasculares. A maioria dos laureados eram norte&#8209;americanos e europeus, e do sexo masculino.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Cardiologia</kwd>
        <kwd>Pr&#234;mio Nobel</kwd>
        <kwd>Hist&#243;ria</kwd>
        <kwd>Doen&#231;as Cardiovasculares / tend&#234;ncias</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>O Pr&#234;mio Nobel foi criado por Alfred Nobel (1833-1896) (<xref ref-type="fig" rid="f04">Figura 1</xref>)<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B02">2</xref>. Em seu testamento, o pesquisador sueco determinou a cria&#231;&#227;o de uma funda&#231;&#227;o com seu nome, cujo objetivo principal seria premiar, a cada ano, pessoas que prestassem grandes servi&#231;os &#224; humanidade nas &#225;reas de paz/diplomacia, literatura, qu&#237;mica, f&#237;sica e fisiologia/medicina. Os primeiros pr&#234;mios foram entregues em 1901 e o primeiro ganhador na &#225;rea de medicina foi Emil Adolf von Behring por seus trabalhos com soro antidift&#233;rico<xref ref-type="bibr" rid="B01">1</xref>. Desde essa data, j&#225; foram 876 laureados, sendo 104 pr&#234;mios e 204 pesquisadores em medicina ou fisiologia<xref ref-type="bibr" rid="B01">1</xref>.</p>
        <fig id="f04">
          <label>Figura 1</label>
          <caption>
            <title>Logomarca do Pr&#234;mio Nobel.</title>
          </caption>
          <attrib>Fonte: <ext-link ext-link-type="uri" xlink:href="http://en.wikipedia.org/wiki/Nobel_Prize">http://en.wikipedia.org/wiki/Nobel_Prize</ext-link>
					</attrib>
          <graphic xlink:href="1678-4170-abc-105-02-0188-50041-gf01-pt.jpg"/></fig>
        <p>O objetivo do presente estudo foi revisar as principais descobertas cient&#237;ficas contempladas pelo Pr&#234;mio Nobel que contribu&#237;ram, direta ou indiretamente, para os avan&#231;os na fisiopatologia, no diagn&#243;stico e no tratamento das doen&#231;as cardiovasculares.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <p>Realizou-se uma busca n&#227;o sistem&#225;tica dos principais ganhadores do Pr&#234;mio Nobel entre 1901 e 2013. A lista de laureados foi delineada a partir do <italic>site</italic> do Pr&#234;mio Nobel<xref ref-type="bibr" rid="B03">3</xref> e, posteriormente, informa&#231;&#245;es sobre os autores e suas pesquisas foram buscadas na base de dados <italic>Medline/ PubMed</italic>. Al&#233;m disso, pela natureza peculiar da pesquisa envolvendo dados hist&#243;ricos e bibliogr&#225;ficos, foi utilizado o buscador <italic>Google</italic>, utilizando como descritores os nomes dos pesquisadores laureados com o Pr&#234;mio Nobel. Os resultados est&#227;o apresentados por ordem cronol&#243;gica crescente.</p>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <sec>
          <title>Uma breve hist&#243;ria do Pr&#234;mio Nobel</title>
          <p>Para muitos historiadores, o interesse de Alfred Nobel pela medicina vinha de uma sa&#250;de debilitada<xref ref-type="bibr" rid="B02">2</xref>. H&#225; relatos de dispepsia, cefaleia e crises de depress&#227;o. Na idade adulta, ele teria sofrido de coronariopatia, com epis&#243;dios frequentes de angina. Seus m&#233;dicos recomendaram que usasse nitroglicerina, subst&#226;ncia que Nobel manipulava na ind&#250;stria de explosivos, mas ele teria recusado. No fim da vida, sofreu um acidente vascular cerebral e teve que conviver com sequelas motoras. C&#233;tico e desconfiado, Nobel expressou em seu testamento o desejo de que, ap&#243;s sua morte, suas veias fossem &#8220;abertas&#8221; e os sinais de morte confirmados por &#8220;m&#233;dicos competentes&#8221;, antes que o corpo fosse enviado &#224; crema&#231;&#227;o<xref ref-type="bibr" rid="B01">1</xref>.</p>
          <p>A escolha de Nobel pelo Instituto Karolinska em seu testamento surpreendeu muitos cientistas. Esse instituto foi criado em 1810 a partir da fus&#227;o de uma escola m&#233;dica e de um pequeno centro de cirurgia, onde barbeiros eram treinados para realizar amputa&#231;&#245;es. Durante anos n&#227;o teve o <italic>status</italic> de faculdade de medicina e dependia de um conv&#234;nio com a Universidade de Uppsala, na Su&#233;cia, para a forma&#231;&#227;o de profissionais<xref ref-type="bibr" rid="B01">1</xref>. Atualmente, o instituto &#233; um dos principais centros de medicina assistencial e de pesquisa em toda Europa. Cinco ganhadores do Pr&#234;mio Nobel, ao longo dos &#250;ltimos 120 anos, s&#227;o oriundos desse instituto<xref ref-type="bibr" rid="B01">1</xref>.</p>
        </sec>
        <sec>
          <title>O Pr&#234;mio Nobel e a cardiologia</title>
          <p>Na &#225;rea da cardiologia, mais especificamente em Insufici&#234;ncia Card&#237;aca (IC), o conhecimento da hist&#243;ria do Pr&#234;mio Nobel ajuda a entender importantes avan&#231;os diagn&#243;sticos e terap&#234;uticos feitos nos &#250;ltimos 120 anos (<xref ref-type="table" rid="t02">Quadro 1</xref>). O primeiro laureado nessa &#225;rea foi Alexis Carrel, por suas descobertas relacionadas a sutura dos vasos sangu&#237;neos, importante etapa no posterior desenvolvimento da cirurgia card&#237;aca<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B03">3</xref>. Apenas um brasileiro, que viveu na Inglaterra, foi laureado. Chama-se Peter Medawar e realizou pesquisas na &#225;rea de imunossupress&#227;o, com futura aplicabilidade no transplante renal e card&#237;aco<xref ref-type="bibr" rid="B04">4</xref><sup>,</sup><xref ref-type="bibr" rid="B05">5</xref>.</p>
          <table-wrap id="t02">
            <label>Quadro 1</label>
            <caption>
              <title>Principais descobertas cient&#237;ficas contempladas pelo Pr&#234;mio Nobel em Fisiologia ou Medicina relacionadas &#224; Cardiologia</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>Ano</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>Autor</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>Pr&#234;mio</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>1912</td>
                  <td align="center">Alexis Carrel</td>
                  <td align="center">Trabalho em sutura vascular e transplante de vasos sangu&#237;neos e &#243;rg&#227;os</td>
                </tr>
                <tr>
                  <td>1924</td>
                  <td align="center">Willem Einthoven</td>
                  <td align="center">Eletrocardiograma</td>
                </tr>
                <tr>
                  <td>1953</td>
                  <td align="center">Hans Adolf Krebs</td>
                  <td align="center">Ciclo do &#225;cido c&#237;trico (e ciclo de Krebs)</td>
                </tr>
                <tr>
                  <td>1956</td>
                  <td align="center">Werner Forssmann, Andre Cournard and Dickinson W. Richards</td>
                  <td align="center">Cateterismo card&#237;aco</td>
                </tr>
                <tr>
                  <td>1960</td>
                  <td align="center">Frank Burnet and Peter Medawar</td>
                  <td align="center">Descoberta do mecanismo de toler&#226;ncia imunol&#243;gica</td>
                </tr>
                <tr>
                  <td>1964</td>
                  <td align="center">Konrad Bloch and Feodor Lynen</td>
                  <td align="center">Entendimento do metabolismo do colesterol</td>
                </tr>
                <tr>
                  <td>1979</td>
                  <td align="center">Allan Cormack and Godfrey Hounsfield</td>
                  <td align="center">T&#233;cnicas de tomografia computadorizada</td>
                </tr>
                <tr>
                  <td>1982</td>
                  <td align="center">Bengt Samuelsson, Sune Bergstr&#246;m and John Vane</td>
                  <td align="center">"Descobridores" dos inibidores da enzima conversora de angiotensina</td>
                </tr>
                <tr>
                  <td>1985</td>
                  <td align="center">Michael Brown and Joseph Goldstein</td>
                  <td align="center">Descobrimento dos receptores do LDL-colesterol</td>
                </tr>
                <tr>
                  <td>1988</td>
                  <td align="center">James Black, Gertrude Elion and George Hitchings</td>
                  <td align="center">Desenvolvimento dos betabloqueadores</td>
                </tr>
                <tr>
                  <td>1990</td>
                  <td align="center">Joseph Edward Murray and Edward Thomas</td>
                  <td align="center">Desenvolvimento do transplante de &#243;rg&#227;os e tecidos</td>
                </tr>
                <tr>
                  <td>1998</td>
                  <td align="center">Robert Furchgott, Ferid Murad and Louis Ignarro</td>
                  <td align="center">Descobertas sobre o &#243;xido n&#237;trico</td>
                </tr>
                <tr>
                  <td>2003</td>
                  <td align="center">Paul Lauterbur and Peter Mansfield</td>
                  <td align="center">Resson&#226;ncia magn&#233;tica</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn>
                <p>LDL: lipoprote&#237;na de baixa densidade.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>A despeito de Carlos Chagas ter pesquisado e descoberto o agente etiol&#243;gico, o vetor, o modo de transmiss&#227;o e as formas cl&#237;nicas da tripanossom&#237;ase, um feito &#250;nico na ci&#234;ncia mundial, algumas vezes ele concorreu ao Nobel e n&#227;o teve &#234;xito. H&#225; hip&#243;teses que tentam explicar o porqu&#234; uma contribui&#231;&#227;o genuinamente brasileira na &#225;rea da cardiologia n&#227;o foi contemplada<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref>.</p>
        </sec>
        <sec>
          <title>Principais estudos com import&#226;ncia para a Cardiologia contemplados com o Pr&#234;mio Nobel</title>
          <sec>
            <title>Alexis Carrel &#8211; 1912: sutura dos vasos sangu&#237;neos</title>
            <p>Alexis Carrel, natural de Sainte-Foy-l&#232;s-Lyon, Fran&#231;a, graduou-se em medicina pela Faculdade de Medicina de Lyon em 1893 e concluiu o doutorado em 1900, com uma pesquisa sobre suturas em vasos sangu&#237;neos. Lecionou Anatomia e Cirurgia na Universidade de Lyons e mudou-se para os Estados Unidos em 1904, onde trabalhou na Universidade de Chicago. Posteriormente, filiou-se ao <italic>Rockefeller Institute for Medical Research</italic>, em Nova Iorque, onde realizou a maior parte dos experimentos que o conduziram ao Pr&#234;mio Nobel em Fisiologia ou Medicina em 1912. Serviu ao corpo m&#233;dico do Ex&#233;rcito franc&#234;s durante a I Guerra Mundial (1914-1918), onde utilizou com sucesso o m&#233;todo <italic>Carrel-Dakin</italic> de irriga&#231;&#227;o constante de feridas com solu&#231;&#227;o antiss&#233;ptica, que diminu&#237;ram mortes e amputa&#231;&#245;es<xref ref-type="bibr" rid="B01">1</xref><sup>-</sup><xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B08">8</xref>.</p>
            <p>Seus primeiros trabalhos foram sobre t&#233;cnicas de cirurgia em vasos sangu&#237;neos e anastomoses arteriovenosas. A partir de 1908, desenvolveu m&#233;todos para transplantes e criopreserva&#231;&#227;o de &#243;rg&#227;os<xref ref-type="bibr" rid="B01">1</xref><sup>-</sup><xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B08">8</xref>. Em 1935, criou um sistema para suprimento est&#233;ril de oxig&#234;nio e preserva&#231;&#227;o de &#243;rg&#227;os removidos do corpo. Tamb&#233;m colaborou com outros pesquisadores para o desenvolvimento da cirurgia card&#237;aca de valvotomia e cultura de c&#233;lulas de sarcoma. Publicou os livros <italic>The culture of organs</italic> e <italic>Treatment of infected wounds</italic><xref ref-type="bibr" rid="B01">1</xref><sup>-</sup><xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B08">8</xref>. A sutura dos vasos sangu&#237;neos foi fundamental para, anos depois, haver o desenvolvimento das cirurgias vasculares.</p>
          </sec>
          <sec>
            <title>Willem Einthoven &#8211; 1924: o eletrocardiograma</title>
            <p>Willem Einthoven nasceu em 21 de maio de 1860 na ilha de Java, atual Indon&#233;sia, e se mudou para a Holanda, em 1870, onde se formou m&#233;dico na Universidade de Utrecht, uma das mais antigas e tradicionais na Europa. Fisiologista, no in&#237;cio do s&#233;culo 20, publicou diversos trabalhos sobre o uso do galvan&#244;metro no registro do eletrocardiograma (ECG) humano, servindo como base para os aparelhos atuais. O equipamento original pesava mais de 270 kg e era operado por v&#225;rias pessoas em seu laborat&#243;rio. Realizou a descri&#231;&#227;o das ondas P, QRS e T, e de suas altera&#231;&#245;es em diversas doen&#231;as, notadamente nas valvopatias. Mostrando grande sabedoria, escreveu, ap&#243;s suas pesquisas iniciais: &#8220;n&#227;o se deve usar a forma do eletrocardiograma, pelo menos exclusivamente, para diagnosticar altera&#231;&#245;es valvares, porque o ECG &#233; express&#227;o da contra&#231;&#227;o do m&#250;sculo card&#237;aco e s&#243; se altera na medida em que uma falha no funcionamento valvular exer&#231;a influ&#234;ncia sobre tal contra&#231;&#227;o&#8221;<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B02">2</xref><sup>,</sup><xref ref-type="bibr" rid="B09">9</xref>.</p>
            <p>Al&#233;m do ECG, Einthoven teve papel importante no desenvolvimento do fonocardiograma<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B02">2</xref><sup>,</sup><xref ref-type="bibr" rid="B09">9</xref>. Esse aparelho, hoje pe&#231;a de museu em muitas escolas m&#233;dicas, foi fundamental no exame complementar &#224; proped&#234;utica m&#233;dica. Antes da inven&#231;&#227;o do ecocardiograma, era por meio da ausculta e do fonocardiograma que muitos diagn&#243;sticos de valvopatias eram definidos. As doen&#231;as orovalvares foram, at&#233; o in&#237;cio do s&#233;culo 20, uma das mais importantes causas de IC, principalmente aquelas de origem reum&#225;tica.</p>
          </sec>
          <sec>
            <title>Hans Adolf Krebs &#8211; 1953: ciclo de Krebs</title>
            <p>Hans Adolf Krebs foi um m&#233;dico nascido em 25 de agosto de 1900, em Hildeshiem, norte da Alemanha<xref ref-type="bibr" rid="B10">10</xref>. Serviu como militar do ex&#233;rcito alem&#227;o na Primeira Guerra Mundial. Apesar de j&#225; graduado em medicina, precisou se exilar da Alemanha na d&#233;cada de 1930, devido &#224; sua descend&#234;ncia judaica. Escolheu morar na Inglaterra, onde desenvolveu suas pesquisas relacionadas &#224; fisiologia celular. Descreveu, em parceria com outros pesquisadores, o ciclo da ureia, o ciclo do &#225;cido c&#237;trico e, principalmente, a respira&#231;&#227;o celular, com produ&#231;&#227;o de Trifosfato de Adenosina (ATP) a partir de glicose e oxig&#234;nio<xref ref-type="bibr" rid="B10">10</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref>. Em sua homenagem, essa sequ&#234;ncia de rea&#231;&#245;es bioqu&#237;micas ficou conhecida como &#8220;ciclo de Krebs&#8221;.</p>
            <p>H&#225; muito j&#225; se sabe que as mitocondriopatias s&#227;o um grupo de doen&#231;as relacionadas &#224; disfun&#231;&#227;o neuromuscular e &#224; miocardiopatia<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref>. Al&#233;m disso, na cardiologia, o estudo do funcionamento das mitoc&#244;ndrias no mi&#243;cito &#233; uma nova fronteira de pesquisa, chamada por alguns de &#8220;bioenerg&#233;tica mitocondrial&#8221;<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref>. Uma das &#225;reas em destaque &#233; a IC, devido ao papel do metabolismo aer&#243;bico no desempenho mioc&#225;rdico. Est&#227;o em desenvolvimento f&#225;rmacos que atuem nas vias mitocondriais, corrigindo eventuais disfun&#231;&#245;es, e se espera que eles possam melhorar a fun&#231;&#227;o mioc&#225;rdica<xref ref-type="bibr" rid="B14">14</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref>.</p>
          </sec>
          <sec>
            <title>Werner Otto Theodor Forssmann, Andr&#233; Cournard e Dickinson Richards &#8211; 1956: cateterismo card&#237;aco</title>
            <p>A hist&#243;ria do cateterismo card&#237;aco teve seu in&#237;cio em 1711, a partir dos trabalhos de Stephen Hales, que inseriu tubos nos dois ventr&#237;culos de um cavalo<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B16">16</xref><sup>-</sup><xref ref-type="bibr" rid="B19">19</xref>. No s&#233;culo 19, o cateterismo card&#237;aco continuou com os trabalhos de Claude Bernard, pai da fisiologia moderna; sofisticou-se com a habilidade de Chauveau e Marey; e come&#231;ou a ser aplicado no cora&#231;&#227;o humano pelo arrojo de Forssmann em 1929, tornando-se terap&#234;utico em 1966<xref ref-type="bibr" rid="B20">20</xref>. Segundo Cournnand<xref ref-type="bibr" rid="B17">17</xref>, o cateterismo card&#237;aco pode ser considerado a &#8220;chave que abriu a fechadura para desvendar os segredos do cora&#231;&#227;o&#8221;. Devido ao avan&#231;o da t&#233;cnica proposta pelos laureados, atualmente o estudo hemodin&#226;mico possuiu aplicabilidade no diagn&#243;stico, tratamento e acompanhamento das doen&#231;as cardiovasculares &#8722; entre elas, a Doen&#231;a Arterial Coronariana (DAC) e a IC.</p>
            <p>O Pr&#234;mio Nobel de Fisiologia ou Medicina de 1956 foi atribu&#237;do a tr&#234;s pesquisadores, por realizarem pesquisas com cateterismo que revolucionaram os estudos sobre as doen&#231;as card&#237;acas<xref ref-type="bibr" rid="B01">1</xref>. Eles se inconformavam com a precariedade dos m&#233;todos semiol&#243;gicos, cujos diagn&#243;sticos proporcionados eram contrariados pelas necr&#243;psias, o que serviu como motiva&#231;&#227;o para iniciarem seus estudos<xref ref-type="bibr" rid="B01">1</xref>.</p>
            <p>Werner Forssmann foi um m&#233;dico alem&#227;o, nascido em Berlim, que desenvolveu a hip&#243;tese de que um cateter pudesse ser inserido pelos vasos sangu&#237;neos at&#233; o cora&#231;&#227;o, com o objetivo de injetar medica&#231;&#245;es, realizar exames contrastados e aferir as press&#245;es cavit&#225;rias. Com o intuito de testar sua hip&#243;tese, realizou o primeiro cateterismo humano em si pr&#243;prio, guiando um cateter at&#233; seu &#225;trio esquerdo com o aux&#237;lio de um aparelho de radioscopia<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B16">16</xref><sup>-</sup><xref ref-type="bibr" rid="B19">19</xref>.</p>
            <p>Andre Cournard, nascido em Paris, Fran&#231;a, e Dickinson Richards, de Orange, Estados Unidos, foram m&#233;dicos que trabalharam no desenvolvimento da t&#233;cnica do cateterismo card&#237;aco, com &#234;nfase nas doen&#231;as pulmonares e nos padr&#245;es de choque circulat&#243;rio. Descreveram os padr&#245;es de choque, em especial o cardiog&#234;nico e o hemorr&#225;gico (trauma), e analisaram as mudan&#231;as hemodin&#226;micas com o tratamento, seja por reposi&#231;&#227;o vol&#234;mica ou pela infus&#227;o de medicamentos<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B16">16</xref><sup>-</sup><xref ref-type="bibr" rid="B19">19</xref>.</p>
          </sec>
          <sec>
            <title>Frank Macfarlane Burnet e Peter Brian Medawar &#8211; 1960: toler&#226;ncia imunol&#243;gica</title>
            <p><italic>Sir</italic> Burnet nasceu na Austr&#225;lia e era filho de pais escoceses. Realizou a gradua&#231;&#227;o em medicina em seu pa&#237;s natal e a p&#243;s-gradua&#231;&#227;o <italic>strictu sensu</italic> na Inglaterra. Especializou-se na &#225;rea de virologia, com importantes pesquisas relacionadas aos v&#237;rus influenza e ao herpes simples. Teve papel fundamental no isolamento viral a partir de tecido humano e nas primeiras tentativas de desenvolver uma vacina para a gripe. Ap&#243;s a Segunda Guerra Mundial, desenvolveu tamb&#233;m pesquisas relacionadas ao sistema imune, com destaque para os mecanismos de autoimunidade e toler&#226;ncia imunol&#243;gica<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B02">2</xref><sup>,</sup><xref ref-type="bibr" rid="B21">21</xref><sup>-</sup><xref ref-type="bibr" rid="B23">23</xref>.</p>
            <p>Peter Brian Medawar (<xref ref-type="fig" rid="f05">Figura 2</xref>) nasceu em Petrop&#243;lis (RJ), e era filho de m&#227;e inglesa e pai liban&#234;s. A fam&#237;lia mudou&#8209;se quando ele tinha apenas 14 anos para a Inglaterra, onde desenvolveu os estudos e sua carreira profissional. Diverg&#234;ncias com o governo brasileiro, que exigia seu alistamento militar obrigat&#243;rio, fizeram-no abrir m&#227;o da nacionalidade brasileira. Formou-se em zoologia em Oxford e iniciou suas pesquisas com transplante durante a Segunda Guerra Mundial. O objeto principal eram os enxertos cut&#226;neos em &#225;rea de pele queimada. Seus estudos levaram &#224; teoria da toler&#226;ncia imunol&#243;gica adquirida, base para o desenvolvimento dos transplantes de &#243;rg&#227;os s&#243;lidos no futuro<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B02">2</xref><sup>,</sup><xref ref-type="bibr" rid="B04">4</xref><sup>,</sup><xref ref-type="bibr" rid="B05">5</xref>. A liga&#231;&#227;o realizada entre suas pesquisas e a cardiologia foi a aplicabilidade de seus resultados com toler&#226;ncia imunol&#243;gica para o futuro desenvolvimento do transplante card&#237;aco.</p>
            <fig id="f05">
              <label>Figura 2</label>
              <caption>
                <title>Foto de Peter Medawar.</title>
              </caption>
              <attrib>Fonte: <ext-link ext-link-type="uri" xlink:href="http://www.nobelprize.org/nobel_prizes/medicine/laureates/1960/medawar-facts.html">http://www.nobelprize.org/nobel_prizes/medicine/laureates/1960/medawar-facts.html</ext-link>
							</attrib>
              <graphic xlink:href="1678-4170-abc-105-02-0188-50041-gf02-pt.jpg"/></fig>
          </sec>
          <sec>
            <title>Konrad Bloch e Feodor Lynen &#8211; 1964: metabolismo do colesterol</title>
            <p>O Pr&#234;mio Nobel de Fisiologia ou Medicina de 1964 foi atribu&#237;do conjuntamente a dois qu&#237;micos alem&#227;es, Konrad Bloch e Feodor Lynen. Bloch nasceu em 21 de janeiro de 1912, em Neisse (agora Nysa), antigamente parte da Alemanha e atualmente na Pol&#244;nia. Graduou-se em engenharia qu&#237;mica no ano de 1934, em Munique. Em 1936, por persegui&#231;&#245;es dos nazistas aos judeus, Bloch emigrou para os Estados Unidos e ingressou no Departamento de Bioqu&#237;mica da Universidade de Col&#250;mbia, onde desenvolveu as pesquisas que o levaram a ser laureado com o Pr&#234;mio Nobel.</p>
            <p>Feodor Lynen nasceu em 6 de abril de 1911, em Munique, na Alemanha, onde concluiu o curso de qu&#237;mica. Desenvolveu toda sua carreira na Alemanha, l&#225; permanecendo mesmo nas grandes guerras mundiais<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref>.</p>
            <p>Mesmo sem executar um trabalho conjunto propriamente dito, ambos os pesquisadores realizaram, em suas universidades, importantes descobertas no mecanismo de regula&#231;&#227;o do colesterol e o metabolismo de &#225;cidos graxos<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref>. Partindo da ideia de que o &#225;cido ac&#233;tico, de lenta rea&#231;&#227;o nos ensaios qu&#237;micos, tinha de apresentar uma rea&#231;&#227;o mais r&#225;pida e espont&#226;nea no organismo, formulou&#8209;se o conceito de &#225;cido ac&#233;tico ativado, no qual, al&#233;m do &#225;cido adenilfosf&#243;rico como fonte de energia, entrava tamb&#233;m a coenzima A. Eles conseguiram determinar n&#227;o s&#243; a estrutura do colesterol como tamb&#233;m a participa&#231;&#227;o da coenzima A na oxida&#231;&#227;o dos &#225;cidos graxos<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref>. Anos mais tarde, essas descobertas foram fundamentais para comprovar a import&#226;ncia do colesterol na aterosclerose e, ainda mais importante, ajudaram no desenvolvimento das estatinas, principal classe de drogas no tratamento da hipercolesterolemia e da doen&#231;a ateroscler&#243;tica.</p>
          </sec>
          <sec>
            <title>Allan M. Cormack e Godfrey Hounsfield &#8211; 1979: tomografia computadorizada</title>
            <p>Allan Cormack era um bioqu&#237;mico e f&#237;sico nuclear sul&#8209;africano nascido em Johanesburgo (&#193;frica do Sul), que se naturalizou americano em 1966. &#201; considerado um dos inventores da tomografia axial computadorizada e dividiu do Pr&#234;mio Nobel de Fisiologia ou Medicina com o professor brit&#226;nico Godfrey Hounsfield. Cormack realizou suas pesquisas em radiologia inicialmente na universidade da Cidade do Cabo at&#233; que emigrou para os Estados Unidos, onde trabalhou em Harvard e na <italic>Tufts University</italic>. L&#225; testou um modelo matem&#225;tico com base na radia&#231;&#227;o X, fundamental para o desenvolvimento da tomografia axial computadorizada<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B25">25</xref>.</p>
            <p><italic>Sir</italic> Godfrey Hounsfield era um engenheiro el&#233;trico, que tinha o cargo de &#8220;inventor&#8221; do <italic>Central Research Laboratories</italic> em Londres. Iniciou sua carreira trabalhando no projeto de radares como arma de guerra e projetou o primeiro computador brit&#226;nico transistorizado em 1958, o &#8220;EMIDEC 1100&#8221;. A partir dos c&#225;lculos matem&#225;ticos sobre radia&#231;&#227;o desenvolvidos por Cormack, desenvolveu a Tomografia Computadorizada (TC) &#8722; tanto que a primeira m&#225;quina para &#8220;escanear&#8221; o c&#233;rebro foi comercializada pela EMI. Tr&#234;s anos depois, desenvolveu a primeira TC para o corpo inteiro. Ele continuou a introduzir melhoramentos na TC e recebeu numerosos pr&#234;mios e honrarias, al&#233;m do Nobel, sendo seu &#250;ltimo pr&#234;mio o t&#237;tulo de <italic>Cavaleiro da Rainha da Inglaterra - Sir</italic>, em 1981<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B25">25</xref>. A TC se desenvolveu muito nos anos seguintes e hoje tem diversas aplica&#231;&#245;es na cardiologia, como, por exemplo, determina&#231;&#227;o da anatomia coronariana e do escore de c&#225;lcio, e na avalia&#231;&#227;o de tromboembolismo pulmonar.</p>
          </sec>
          <sec>
            <title>Bengt Samuelsso, Sune Bergstr&#246;m e John Vane &#8211; 1982: fun&#231;&#227;o das prostaglandinas e desenvolvimento dos inibidores da enzima conversora de angiotensina</title>
            <p>Bengt Ingemar Samuelsso foi um bioqu&#237;mico sueco nascido em 1934 em Halmstad, pesquisador do Instituto Karolinska, na Su&#233;cia, e laureado do Pr&#234;mio Nobel de Fisiologia ou Medicina com seu colega de instituto, o tamb&#233;m bioqu&#237;mico sueco Sune K. Bergstr&#246;m, e com o qu&#237;mico e farmacologista ingl&#234;s John Robert Vane<xref ref-type="bibr" rid="B01">1</xref>. Suas pesquisas envolveram as fun&#231;&#245;es das prostaglandinas, sua purifica&#231;&#227;o, determina&#231;&#227;o da estrutura qu&#237;mica e identifica&#231;&#227;o de seu mecanismo de forma&#231;&#227;o a partir de &#225;cidos graxos insaturados<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B26">26</xref><sup>,</sup><xref ref-type="bibr" rid="B27">27</xref>. Essas informa&#231;&#245;es permitiram a proposi&#231;&#227;o do mecanismo de a&#231;&#227;o do &#225;cido acetilsalic&#237;lico, tratamento praticamente indispens&#225;vel nas doen&#231;as coronarianas.</p>
            <p>Al&#233;m das pesquisas com as prostaglandinas, John Vane tamb&#233;m &#233; considerado um dos &#8220;descobridores&#8221; dos Inibidores da Enzima Conversora de Angiotensina (iECA)<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B26">26</xref><sup>,</sup><xref ref-type="bibr" rid="B27">27</xref>. Ao longo das d&#233;cadas de 1960 e 1970, e com a participa&#231;&#227;o do brasileiro S&#233;rgio Ferreira, Vane e seus colaboradores demonstraram etapas-chave na s&#237;ntese da angiotensina e da bradicinina, que, em 1982, culminaram no lan&#231;amento do primeiro iECA, o captopril<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B26">26</xref><sup>,</sup><xref ref-type="bibr" rid="B27">27</xref>. Essa classe de medicamentos tem papel fundamental na hipertens&#227;o, na IC e na doen&#231;a coronariana.</p>
          </sec>
          <sec>
            <title>Michael Brown e Joseph Goldstein &#8211; 1985: receptores do LDL-colesterol</title>
            <p>Joseph L. Goldstein nasceu em 18 de abril de 1940 em Sumter, na Carolina do Sul, nos Estados Unidos. Inicialmente, graduou-se em qu&#237;mica pela <italic>Washington and Lee University</italic> e, posteriormente, m&#233;dico pela <italic>University of Texas Southwestern Medical Center Dallas</italic>. Foi residente do Hospital Geral de Massachusetts, onde conheceu Michael S. Brown, que, mais tarde, seria seu colaborador e ganharia com ele o Pr&#234;mio Nobel<xref ref-type="bibr" rid="B03">3</xref>. Nos 2 anos seguintes, trabalhou no National Heart, Lung, and Blood Institute dos Estados Unidos, o que teria contribu&#237;do para a aumentar suas habilidades e seu gosto pela experimenta&#231;&#227;o cient&#237;fica na perspectiva da biologia molecular para a doen&#231;a humana<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B28">28</xref><sup>-</sup><xref ref-type="bibr" rid="B30">30</xref>.</p>
            <p>Michael Stuart Brown nasceu em 13 de abril de 1941, no Brooklyn, Nova Iorque. Assim como Goldstein, formou-se primeiro em qu&#237;mica e somente depois em medicina. Tamb&#233;m trabalhou no National Heart, Lung, and Blood Institute dos Estados Unidos, mas na &#225;rea de gastrenterologia e doen&#231;as heredit&#225;rias. No laborat&#243;rio de bioqu&#237;mica, aprendeu t&#233;cnicas de manipula&#231;&#227;o enzim&#225;tica, dentre as quais uma enzima que poderia estar relacionada &#224; hipercolesterolemia familiar<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B28">28</xref><sup>-</sup><xref ref-type="bibr" rid="B30">30</xref>.</p>
            <p>Goldstein e Brown foram laureados pelo Pr&#234;mio Nobel por pesquisas cient&#237;ficas nas quais identificaram receptores na superf&#237;cie das c&#233;lulas que mediam a capta&#231;&#227;o de Lipoprote&#237;na de Baixa Densidade (LDL) circulante no sangue. Al&#233;m disso, descobriram que a hipercolesterolemia heredit&#225;ria familiar grave est&#225; intimamente ligada a esses receptores, pois, com a diminui&#231;&#227;o do n&#250;mero de receptores na membrana, h&#225; uma menor capta&#231;&#227;o do colesterol circulante em forma de LDL, aumentando, assim, os n&#237;veis da subst&#226;ncia na corrente sangu&#237;nea<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B28">28</xref><sup>-</sup><xref ref-type="bibr" rid="B30">30</xref>. Nesse exemplo, mais uma vez, pode-se observar a &#237;ntima rela&#231;&#227;o entre n&#237;vel elevados de colesterol, aterosclerose e cardiopatia isqu&#234;mica.</p>
          </sec>
          <sec>
            <title>James Black, Gertrude Elion e George Hitchings &#8211; 1988: betabloqueadores</title>
            <p>James W. Black, natural de Uddington, Esc&#243;cia, estudou medicina na Universidade de Saint Andrews. Em 1948, iniciou uma investiga&#231;&#227;o sobre receptores adren&#233;rgicos card&#237;acos alfa e beta, que resultou na s&#237;ntese do propranolol, prot&#243;tipo dos betabloqueadores, medica&#231;&#245;es fundamentais para os tratamentos da IC e da doen&#231;a coronariana. Mais tarde, em 1976, concluiu a s&#237;ntese da cimetidina, antagonista de receptor de histamina H2, usada em tratamentos de doen&#231;a p&#233;ptica. Juntamente de James W. Black, os pesquisadores Gertrude B. Elion (Nova Iorque, Estados Unidos) e George H. Hitchings (Hoquiam, Estados Unidos) tamb&#233;m foram laureados com o Nobel de Medicina, pelo desenvolvimento de f&#225;rmacos usados em quimioterapia, antibi&#243;ticos e antivirais<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B31">31</xref>.</p>
          </sec>
          <sec>
            <title>Joseph Edward Murray e Edward Thomas &#8211; 1990: transplante de &#243;rg&#227;os</title>
            <p>Joseph Murray nasceu em 1&#176; de abril de 1919, na cidade de Milford, Estado de Massachusets (Estados Unidos) e faleceu em 2012, devido a um acidente vascular cerebral. Formou-se m&#233;dico na faculdade de medicina de Harvard e especializou-se em cirurgia pl&#225;stica. Serviu nas for&#231;as armadas americanas e teve grande papel no atendimento aos militares feridos na Segunda Guerra Mundial. Durante o atendimento a queimados, observou que muitos pacientes reagiam bem a enxertos de pele de doadores e resolveu desenvolver uma pesquisa relacionada a transplante de &#243;rg&#227;os. Em 23 de dezembro de 1954, participou da equipe que fez o primeiro transplante renal intervivos e, alguns anos ap&#243;s, o primeiro de fonte cadav&#233;rica. Ao longo dos anos, participou de estudos sobre drogas imunossupressoras, como a azatioprina, objetivando reduzir a rejei&#231;&#227;o aos enxertos<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B32">32</xref>.</p>
            <p>Edward Donall Thomas nasceu em 20 de mar&#231;o de 1920, na cidade de Mart, Estado do Texas (Estados Unidos), e faleceu tamb&#233;m em 2012. Formou-se m&#233;dico na faculdade de Harvard e, desde cedo, dedicou-se a estudos laboratoriais relacionados ao transplante de medula &#243;ssea. Em conjunto com Joseph Edward Murray, recebeu o Nobel de Fisiologia ou Medicina, pois seus estudos ajudaram a desenvolver o transplante de &#243;rg&#227;os e tecidos. No campo da IC, o transplante card&#237;aco foi indicado para os pacientes que permanecem muito sintom&#225;ticos apesar do tratamento cl&#237;nico otimizado, tendo sido realizado pela primeira vez na hist&#243;ria na &#193;frica do Sul pelo m&#233;dico Christiaan Barnard<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B32">32</xref>.</p>
          </sec>
          <sec>
            <title>Robert F. Furchgott, Ferid Murad e Louis J. Ignarro &#8211; 1998: &#243;xido n&#237;trico</title>
            <p>O Pr&#234;mio Nobel de Fisiologia ou Medicina 1998 foi atribu&#237;do conjuntamente a Robert F. Furchgott (Charleston, Estados Unidos), Louis J. Ignarro (Nova Iorque, Estados Unidos) e Ferid Murad (Whiting, Estados Unidos) pelas descobertas sobre o &#211;xido N&#237;trico (NO) como uma mol&#233;cula sinalizadora no sistema cardiovascular<xref ref-type="bibr" rid="B01">1</xref>. O NO &#233; um g&#225;s sol&#250;vel presente naturalmente em nosso organismo, que atua na sinaliza&#231;&#227;o de v&#225;rios processos biol&#243;gicos. A s&#237;ntese de NO se realiza por a&#231;&#227;o de uma enzima, a NO Sintetase (NOS), a partir dos amino&#225;cidos L-arginina e L-citrulina, necessitando, para essa rea&#231;&#227;o enzim&#225;tica, da presen&#231;a de dois cofatores, o oxig&#234;nio e o Fosfato Dinucleot&#237;deo Adenina Nicotinamida (NADPH). Existem tr&#234;s formas de NOS, duas delas denominadas constitutivas e dependentes do c&#225;lcio (cNOS), que s&#227;o a endotelial e a neuronal, as quais sintetizam NO em condi&#231;&#245;es normais, e forma a independente do c&#225;lcio (iNOS), que n&#227;o se expressa ou o faz em muita pouca quantidade em condi&#231;&#245;es fisiol&#243;gicas. O NO tem papel importante na homeostase endotelial, contribuindo com suas propriedades vasodilatadoras e anticoagulantes. H&#225; evid&#234;ncias de que a diminui&#231;&#227;o da produ&#231;&#227;o de NO &#233; um fator importante nos epis&#243;dios isqu&#234;micos em pacientes com coronariopatia e outras sugerindo que o NO possa exercer a&#231;&#245;es antiateroscler&#243;ticas. Al&#233;m disso, os nitratos, um dos f&#225;rmacos mais utilizados em doen&#231;a coronariana e na IC, atuam aumentando, indiretamente, a biodisponibilidade de NO<xref ref-type="bibr" rid="B33">33</xref><sup>-</sup><xref ref-type="bibr" rid="B36">36</xref>.</p>
          </sec>
          <sec>
            <title>Paul C. Lauterbur e Peter Mansfield &#8211; 2003: resson&#226;ncia magn&#233;tica</title>
            <p>Paul Lauterbur nasceu em 6 de maio de 1929 nos Estados Unidos, tendo feito seu doutoramento em Qu&#237;mica na Universidade de Pittsburgh, na Pensilv&#226;nia (Estados Unidos). Ao longo da sua carreira recebeu v&#225;rios pr&#234;mios pelo seu trabalho relacionado com a resson&#226;ncia magn&#233;tica, entre eles a medalha de ouro da <italic>Society of Magnetic Resonance in Medicine</italic> em 1982, o Pr&#234;mio Europeu de Resson&#226;ncia Magn&#233;tica em 1986, o <italic>Internacional Society for Magnetic Resonance in Medicine Award</italic> em 1992, a medalha de ouro do Congresso Europeu de Radiologia em 1999, o <italic>NAS Award for Chemistry in Service to Society</italic> em 2001 e o Pr&#234;mio Nobel da Fisiologia ou Medicina em 2003, juntamente do ingl&#234;s Sir Peter Mansfield<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B37">37</xref><sup>-</sup><xref ref-type="bibr" rid="B39">39</xref>.</p>
            <p>Peter Mansfield nasceu em 9 de outubro de 1933 em Londres e fez doutorado em F&#237;sica em sua cidade natal em 1962. No percurso da sua carreira como investigador recebeu v&#225;rios pr&#234;mios, entre eles, a medalha de ouro da Sociedade de Resson&#226;ncia Magn&#233;tica em Medicina no ano de 1983, o Pr&#234;mio Europeu de Resson&#226;ncia Magn&#233;tica em 1988, o t&#237;tulo de <italic>Sir</italic> da Coroa Brit&#226;nica em 1993, a medalha de ouro do Congresso Europeu de Radiologia e da Associa&#231;&#227;o Europeia de Radiologia em 1995, e o Pr&#234;mio Nobel da Fisiologia e da Medicina, pelas suas descobertas relacionadas com imagens de resson&#226;ncia magn&#233;tica nuclear, em 2003<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B37">37</xref><sup>-</sup><xref ref-type="bibr" rid="B39">39</xref>.</p>
            <p>A partir das descobertas iniciais de Lauterbur e Mansfield, a resson&#226;ncia magn&#233;tica se desenvolveu e hoje tem vasta aplica&#231;&#227;o na cardiologia. &#201; considerada, por exemplo, o exame padr&#227;o-ouro na avalia&#231;&#227;o n&#227;o invasiva do mioc&#225;rdio e da fun&#231;&#227;o card&#237;aca.</p>
          </sec>
        </sec>
        <sec>
          <title>Considera&#231;&#245;es Especiais</title>
          <sec>
            <title>Carlos Chagas &#8211; 1911: um grande injusti&#231;ado em rela&#231;&#227;o ao Pr&#234;mio Nobel</title>
            <p>Carlos Chagas (<xref ref-type="fig" rid="f06">Figura 3</xref>) foi o primeiro pesquisador da hist&#243;ria cient&#237;fica mundial a descrever o ciclo completo de uma doen&#231;a, hoje conhecida como doen&#231;a de Chagas<xref ref-type="bibr" rid="B40">40</xref>. Suas pesquisas com <italic>Trypanosoma cruzi</italic> se iniciaram entre os anos de 1907 e 1909, quando foi enviado ao interior de Minas Gerais para auxiliar no combate &#224; mal&#225;ria entre os trabalhadores da Estrada de Ferro Central do Brasil<xref ref-type="bibr" rid="B07">7</xref>. Em 1909, ele identificou o parasita no sangue de uma crian&#231;a com &#8220;febre, anemia, edema e linfadenopatia generalizada&#8221; e, posteriormente, descreveu o ciclo de vida do <italic>T. cruzi</italic><xref ref-type="bibr" rid="B07">7</xref>. Auxiliado por uma pequena equipe, modificou a hist&#243;ria como um cientista inspirador para a era do conhecimento, pois foi capaz de tra&#231;ar um perfil cl&#237;nico a partir de suas pr&#243;prias observa&#231;&#245;es.</p>
            <fig id="f06">
              <label>Figura 3</label>
              <caption>
                <title>Foto de Carlos Chagas. Fonte: Lagoeiro B, Gemal P. Carlos Chagas. Um homem, uma doen&#231;a, uma hist&#243;ria. Niter&#243;i: Ed. UFF; 2012.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-105-02-0188-50041-gf03-pt.jpg"/></fig>
            <p>Ao longo de sua carreira, recebeu homenagens de relev&#226;ncia nacional, como cargos de gest&#227;o sanit&#225;ria p&#250;blica, e tamb&#233;m internacional, como o pr&#234;mio Schaudinn, na Alemanha, contemplado pela descoberta mais importante de protozoologia. Por esses motivos, por quatro vezes recebeu indica&#231;&#227;o ao Pr&#234;mio Nobel, mas nenhuma delas se concretizou. Pesquisadores e historiadores buscaram, entre outras fontes, arquivos da Fun&#231;&#227;o Oswaldo Cruz e do Instituto Karolinska para identificar os motivos da n&#227;o premia&#231;&#227;o de Chagas<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref><sup>,</sup><xref ref-type="bibr" rid="B41">41</xref><sup>-</sup><xref ref-type="bibr" rid="B43">43</xref>. Bestetti e cols.<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref><sup>,</sup><xref ref-type="bibr" rid="B41">41</xref><sup>,</sup><xref ref-type="bibr" rid="B42">42</xref>, em seu conjunto de publica&#231;&#245;es hist&#243;ricas, embasaram solidamente os motivos pelos quais Chagas n&#227;o foi laureado pelo Pr&#234;mio Nobel. Estes pesquisadores foram, inclusive, ao instituto sueco avaliar pessoalmente os documentos originais da &#233;poca; suas pesquisas, em prestigiados peri&#243;dicos internacionais, est&#227;o menos divulgadas do que deveriam na cardiologia brasileira.</p>
            <p>Gunnar Hedr&#232;n foi o membro do conselho do Instituto Karolinska que analisou e emitiu um parecer na primeira indica&#231;&#227;o de Chagas ao Pr&#234;mio Nobel, em 1921<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref>. Apesar de n&#227;o haver um parecer formal por escrito, a an&#225;lise de documentos da &#233;poca sugere que o conselheiro n&#227;o valorizou a descoberta de Chagas<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref>. Apesar de hoje reconhecido como not&#243;rio pesquisador, Chagas tinha opositores na Am&#233;rica do Sul e no Brasil. Um grupo ligado ao Instituto de Bacteriologia de Buenos Aires, incluindo um brasileiro, insistia, nos primeiros anos da descoberta de Chagas, que n&#227;o haveria liga&#231;&#227;o entre os sintomas relatados por Chagas e a presen&#231;a de <italic>T. cruzi</italic><xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B44">44</xref>. Outro grupo, ligado &#224; pr&#243;pria Funda&#231;&#227;o Oswaldo Cruz e &#224; Faculdade de Medicina do Rio de Janeiro, discordava de Chagas por raz&#245;es pol&#237;ticas e, em diversas oportunidades, questionaram a import&#226;ncia da tripanossom&#237;ase<xref ref-type="bibr" rid="B06">6</xref>. Entre os opositores, estavam Figueiredo de Vasconcellos, Cardoso Fontes e Pl&#237;nio Marques<xref ref-type="bibr" rid="B06">6</xref>. Chagas tamb&#233;m perdeu prest&#237;gio entre a popula&#231;&#227;o local por medidas impopulares na &#233;poca em que foi Diretor de Sa&#250;de P&#250;blica, um cargo equivalente na &#233;poca ao &#8220;Ministro da Sa&#250;de&#8221;. A obrigatoriedade da vacina para var&#237;ola foi uma dessas medidas mais criticadas, sendo, inclusive, motivo de uma revolta popular<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B42">42</xref>. Por fim, criticam-se os m&#233;todos utilizados pelo ent&#227;o presidente do Instituto Karolinska, J. E. Johansson. Sugere-se que ele valorizou excessivamente pesquisas ligadas &#224; fisiologia em detrimento &#224;quelas relacionadas &#224; medicina cl&#237;nica<xref ref-type="bibr" rid="B42">42</xref>.</p>
            <p>Uma nova indica&#231;&#227;o e uma eventual premia&#231;&#227;o com o Nobel, ap&#243;s a morte, n&#227;o s&#227;o mais esperados. Resta, somente, &#224; luz do centen&#225;rio da descoberta de Chagas, o orgulho pelo grande brasileiro que, com todas as honras e os m&#233;ritos, fez tamanha contribui&#231;&#227;o &#224; humanidade.</p>
          </sec>
          <sec>
            <title>Bernard Lown &#8211; um brilhante cardiologista cl&#237;nico ganhador do Nobel da Paz de 1985</title>
            <p>Bernard Lown nasceu em 7 de junho de 1921, na cidade de Utena, na Litu&#226;nia, e mudou-se aos 13 anos com a fam&#237;lia para o Estado de Maine, nos Estados Unidos, onde se formou m&#233;dico e concluiu especializa&#231;&#227;o em cardiologia no atual <italic>Brigham and Women&#8217;s Hospital</italic>, em Boston<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B45">45</xref>. Em conjunto com o engenheiro Baruch Berkowitz, em 1961, criou a corrente direta no uso do desfibrilador, permitindo maior seguran&#231;a e efic&#225;cia em rela&#231;&#227;o ao ent&#227;o desfibrilador de corrente alternada criado por Paul Zoll. Foi de Lown tamb&#233;m a descoberta do per&#237;odo correto do ciclo card&#237;aco no ECG para a descarga el&#233;trica nas taquiarritmias ventriculares. A essa terapia ele deu o nome de &#8220;cardiovers&#227;o&#8221;. O desfibrilador idealizado por Lown e Berkowitz foi utilizado como terapia padr&#227;o nas arritmias card&#237;acas at&#233; a d&#233;cada de 1980, quando surgiram os modelos com corrente bif&#225;sica. Ele tamb&#233;m tem pesquisas no uso da lidoca&#237;na como antiarr&#237;tmico e na import&#226;ncia do n&#237;vel s&#233;rico de pot&#225;ssio na intoxica&#231;&#227;o digit&#225;lica. A lidoca&#237;na, at&#233; ent&#227;o, era utilizada basicamente como anest&#233;sico local por dentistas. No &#226;mbito da IC, as terapias el&#233;tricas s&#227;o fundamentais na preven&#231;&#227;o da morte s&#250;bita (cuja disfun&#231;&#227;o ventricular &#233; um dos fatores de risco mais importantes) e no tratamento de arritmias sintom&#225;ticas, altamente prevalentes nesse grupo; a digoxina &#233; uma das medica&#231;&#245;es indicadas nos pacientes com fra&#231;&#227;o de eje&#231;&#227;o reduzida e sintom&#225;ticos em classe funcional III ou IV<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B45">45</xref>.</p>
            <p>Apesar de todas essas contribui&#231;&#245;es &#224; medicina, seu Pr&#234;mio Nobel foi conquistado por outros m&#233;ritos: defensor da paz, criou a Associa&#231;&#227;o Internacional de M&#233;dicos contra a Guerra Nuclear, em associa&#231;&#227;o com o ent&#227;o sovi&#233;tico Yevgeniy Chazov. Sua associa&#231;&#227;o de M&#233;dicos para a Paz contou, inclusive, com a participa&#231;&#227;o de brasileiros. Publicou ainda dois famosos livros: <italic>The lost art of healing</italic> (<italic>A perdida arte de curar</italic>) e <italic>Prescription for survival: a doctor's journey to end nuclear madness</italic>. Atualmente &#233; professor em&#233;rito da Universidade de Harvard e fundador do Instituto Lown, cuja miss&#227;o descrita em seu site &#233;: &#8220;ajudar a montar um sistema de sa&#250;de com compaix&#227;o e sustent&#225;vel, onde os m&#233;dicos possam servir como curadores e advogados, onde os pacientes recebem os servi&#231;os de que precisam e protegidos de tratamento desnecess&#225;rio e dano, e em que os incentivos financeiros s&#227;o retirados da tomada de decis&#227;o cl&#237;nica&#8221;<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B45">45</xref>.</p>
          </sec>
        </sec>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>O Pr&#234;mio Nobel tem por objetivo homenagear pesquisadores cujas a&#231;&#245;es e descobertas tenham contribu&#237;do de modo destacado para o progresso e o bem da sociedade. Para a insufici&#234;ncia card&#237;aca, via final de diversas formas de agress&#227;o card&#237;aca, 33 pesquisadores em 16 pr&#234;mios realizaram trabalhos com grande contribui&#231;&#227;o ao seu diagn&#243;stico e tratamento. O Brasil, mesmo com crescente contribui&#231;&#227;o cient&#237;fica nas &#250;ltimas d&#233;cadas, para a fisiologia e a medicina, n&#227;o tem vencedores &#8220;genuinamente&#8221; brasileiros, apesar das as contribui&#231;&#245;es do Dr. Peter Medawar e do Dr. Carlos Chagas &#8722; esse &#250;ltimo injustamente n&#227;o laureado com essa honraria.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="financial-disclosure">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
          </p>
          <p>O estudo est&#225; vinculado ao Programa de P&#243;s-Gradua&#231;&#227;o Stricto Sensu em Ci&#234;ncias Cardiovasculares da Universidade Federal Fluminense.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
