New Horizons in Cardioprotection
2011; Lippincott Williams & Wilkins; Volume: 124; Issue: 10 Linguagem: Inglês
10.1161/circulationaha.111.032698
ISSN1524-4539
AutoresLisa Schwartz Longacre, Robert A. Kloner, Andrew E. Arai, Christopher Baines, Roberto Bolli, Eugene Braunwald, James M. Downey, Raymond J. Gibbons, Roberta A. Gottlieb, Gerd Heusch, Robert B. Jennings, David J. Lefer, Robert M. Mentzer, Elizabeth Murphy, Michel Ovize, Peipei Ping, Karin Przyklenk, Michael N. Sack, Richard S. Vander Heide, Jakob Vinten‐Johansen, Derek M. Yellon,
Tópico(s)Anesthesia and Neurotoxicity Research
ResumoHomeCirculationVol. 124, No. 10New Horizons in Cardioprotection Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBNew Horizons in CardioprotectionRecommendations From the 2010 National Heart, Lung, and Blood Institute Workshop Lisa Schwartz Longacre, PhD, Robert A. Kloner, MD, PhD, Andrew E. Arai, MD, Christopher P. Baines, PhD, Roberto Bolli, MD, Eugene Braunwald, MD, James Downey, PhD, Raymond J. Gibbons, MD, Roberta A. Gottlieb, MD, Gerd Heusch, MD, PhD, Robert B. Jennings, MD, David J. Lefer, PhD, Robert M. Mentzer, MD, Elizabeth Murphy, PhD, Michel Ovize, MD, PhD, Peipei Ping, PhD, Karin Przyklenk, PhD, Michael N. Sack, MD, PhD, Richard S. Vander Heide, MD, PhD, Jakob Vinten-Johansen, PhD and Derek M. Yellon, DSc, PhD Lisa Schwartz LongacreLisa Schwartz Longacre From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Robert A. KlonerRobert A. Kloner From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Andrew E. AraiAndrew E. Arai From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Christopher P. BainesChristopher P. Baines From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Roberto BolliRoberto Bolli From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Eugene BraunwaldEugene Braunwald From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , James DowneyJames Downey From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Raymond J. GibbonsRaymond J. Gibbons From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Roberta A. GottliebRoberta A. Gottlieb From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Gerd HeuschGerd Heusch From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Robert B. JenningsRobert B. Jennings From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , David J. LeferDavid J. Lefer From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Robert M. MentzerRobert M. Mentzer From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Elizabeth MurphyElizabeth Murphy From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Michel OvizeMichel Ovize From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Peipei PingPeipei Ping From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Karin PrzyklenkKarin Przyklenk From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Michael N. SackMichael N. Sack From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Richard S. Vander HeideRichard S. Vander Heide From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). , Jakob Vinten-JohansenJakob Vinten-Johansen From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). and Derek M. YellonDerek M. Yellon From the National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences (L.S.L.) and Division of Intramural Research (A.E.A., E.M., M.N.S.), Bethesda, MD; Good Samaritan Hospital, Los Angeles, CA (R.A.K.); Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.); University of Missouri, Columbia (C.P.B.); University of Louisville, Louisville, KY (R.B.); Harvard University, Boston, MA (E.B.); University of South Alabama, Mobile (J.D.); Mayo Clinic, Rochester, MN (R.J.G.); San Diego State University, San Diego, CA (R.A.G., R.M.M.); University of Essen Medical School, Essen, Germany (G.H.); Duke University, Durham, NC (R.B.J.); Emory University, Atlanta, GA (D.J.L., J.V.-J.); Wayne State University, Detroit, MI (R.M.M., K.P.); University and Hospices Civils of Lyon, Lyon, France (M.O.); University of California, Los Angeles (P.P.); Louisiana State University, New Orleans (R.S.V.H.); and University College London, London, UK (D.M.Y.). Originally published6 Sep 2011https://doi.org/10.1161/CIRCULATIONAHA.111.032698Circulation. 2011;124:1172–1179IntroductionCoronary heart disease is the largest major killer of American men and women and accounted for 1 of every 6 deaths in the United States in 2007.1 The annual incidence of myocardial infarction in the United States is estimated to be 935 000, with 610 000 new cases and 325 000 recurrent attacks. Survivors have a much higher chance of suffering from congestive heart failure, arrhythmias, and sudden cardiac death.Prognosis after an acute myocardial ischemic injury is primarily dependent on the amount of myocardium that undergoes irreversible injury.2–4 Large transmural infarcts yield a higher probability of cardiogenic shock, arrhythmias, adverse remodeling, and development of late chronic heart failure. Although it has been known since the early 1970s that the size of a myocardial infarction can be modified by various therapeutic interventions,5 early coronary artery reperfusion by fibrinolysis or percutaneous coronary intervention, including balloon angioplasty with or without stenting, remains the only established intervention capable of consistently reducing infarct size in humans. Although reperfusion has led to significant advances in patient care and reduction in hospital mortality, delays in seeking medical attention and inherent limitations in initiating fibrinolysis or percutaneous coronary intervention dictate that additional substantive improvements in morbidity and mortality can be achieved only with the development of new adjunctive therapies coupled with reperfusion. In addition, reperfusion therapy itself may induce reperfusion injury, a phenomenon that may encompass stunned myocardium, no-reflow phenomenon, and lethal myocardial cell death. If this injury could be prevented or minimized by administration of adjunctive therapy, then the net benefit of reperfusion could be enhanced.The problem of acute ischemic injury and myocardial infarction is not limited to patients with acute coronary artery syndrome. It remains a major problem in cardiac surgery as well. It is well documented that the incidence of myocardial necrosis after surgery, as determined by creatine kinase MB enzyme release and troponin levels, ranges somewhere between 40% and 60%, and, depending on its clinical definition, the incidence of myocardial infarction after coronary artery bypass graft surgery may be as high as 19%. The intermediate and long-term implications are considerable. In a recent retrospective analysis of 18 908 patients who underwent coronary artery bypass graft surgery and in whom long-term follow-up was available, it was shown that myocardial enzyme elevation within the first 24 hours of surgery was associated with increasing mortality over the course of months to years. This study confirms earlier reports that even small enzyme elevations after surgery are associated with worse long-term outcomes.4Goals of the WorkshopTo expedite progress in cardioprotection against ischemia/reperfusion injury and facilitate translation of promising therapies from preclinical to clinical use, the National Heart, Lung, and Blood Institute (NHLBI) within the National Institutes of Health convened an invitational workshop of leading national and international experts in fundamental, translational, and clinical science on September 20 to 21, 2010, in Rockville, MD. The objectives of the workshop were to (1) identify the highest-priority knowledge gaps and barriers that have prevented the implementation of effective clinical studies on promising cardioprotective technologies; (2) consider approaches that capitalize on current scientific opportunities; (3) focus on areas that require unique NHLBI leadership to promote progress toward translation; and (4) develop recommendations that would provide a strategy to facilitate the translation of experimentally successful cardioprotective therapies developed in basic science studies to patients at risk for acute ischemic myocardial damage. The recommendations generated would be used to guide informed decisions on research priorities and directions in the field of myocardial protection against ischemia/reperfusion injury. Detailed summaries of individual presentations will be published in a focused issue of the Journal of Cardiovascular Pharmacology and Therapeutics. The present article focuses on the gaps in knowledge identified at the workshop and presents the recommendations for clinical and basic studies provided by the workshop participants.Progress Since the 2003 National Heart, Lung, and Blood Institute Working GroupThe workshop was focused on progress made since the 2003 NHLBI Working Group convened on this topic entitled, "Translation of Therapies for Protecting the Heart From Ischemia."6 Consistent with the recommendations of the 2003 Working Group was the recent NHBLI support of a multicenter Consortium for Preclinical Assessment of Cardioprotective Therapies (CAESAR) to perform systematic preclinical testing of cardioprotective therapies with the use of standardized and randomized protocols in multiple species, performed by blinded investigators, and analyzed by blinded data analysis cores and a single statistical core, as is done for randomized, multicenter clinical trials. Furthermore, the consortium offers unique opportunities for productive collaborations with industrial partners who, along with investigators in academia, will have the opportunity to propose therapies for testing in the consortium. The workshop participants expressed enthusiasm for the potential of this consortium as a means to move the field of cardioprotection forward and identify therapies that are truly efficacious in more than 1 animal model of human disease and more than 1 laboratory.Another key recommendation from the 2003 Working Group was a need for further studies to test the clinical benefit of adenosine. Since 2003, the final results of the Acute Myocardial Infarction Study of Adenosine (AMISTAD) 2 have been reported.7 In this study, >2100 ST-segment elevation myocardial infarction patients receiving reperfusion therapy were randomized to a 3-hour infusion of either intravenous adenosine (50 or 70 μg/kg per minute) or placebo. There was no difference in the primary end point (congestive heart failure or death within 6 months) between placebo and adenosine. In a prospective substudy, the median infarct size assessed by single photon emission computed tomography (SPECT) was 27% of the left ventricle for the placebo group; it was 11% in the 70-μg/kg per minute adenosine group (P=0.023) and 23% in the 50-μg/kg per minute (P=NS) group. The reduction of infarct size at the higher dose of adenosine confirmed the previous AMISTAD 1 study.8 The authors of AMISTAD 2 stated that "a likely explanation for failure for the trial to demonstrate a clinical benefit was that it was underpowered, since sample size calculation was based on a reduction of events in the pooled adenosine group by 25%. The reduction observed was only 11%."7 In a subsequent analysis of patients reperfused in a timely fashion, adenosine therapy was associated with lower rates of death compared with placebo.9The participants acknowledged promising small clinical trials that suggested the benefit of certain agents and mechanical interventions, sometimes within specific subpopulations, including postconditioning,10 cyclosporine,11 remote conditioning,12 hypothermia,13 hyperoxemia,14 and others. The present workshop participants strongly supported clinical trials of new and potentia
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