Circulation Research. 2004;95:125-134
doi: 10.1161/01.RES.0000137171.97172.d7
doi: 10.1161/01.RES.0000137171.97172.d7
© 2004 American Heart Association, Inc.
Special Article |
Myocardial Protection at a Crossroads
The Need for Translation Into Clinical Therapy
From the Heart Research Program, Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health & Human Services, Bethesda, Md.
Correspondence to David A. Lathrop, PhD, Leader, Arrhythmia, Ischemia, and Sudden Cardiac Death, Scientific Research Group, Heart Research Program, Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health & Human Services, Bethesda, MD 20892. E-mail LathropD{at}nhlbi.nih.gov
Over the past 30 years, hundreds of experimental interventions (both pharmacologic and nonpharmacologic) have been reported to protect the ischemic myocardium in experimental animals; however, with the exception of early reperfusion, none has been translated into clinical practice. The National Heart, Lung, and Blood Institute convened a working group to discuss the reasons for the failure to translate potential therapies for protecting the heart from ischemia and reperfusion and to recommend new approaches to accomplish this goal. The Working Group concluded that cardioprotection in the setting of acute myocardial infarction, cardiac surgery, and cardiac arrest is at a crossroads. Present basic research approaches to identify cardioprotective therapies are inefficient and counterproductive. For 3 decades, significant resources have been invested in single-center studies that have often yielded inconclusive results. A new paradigm is needed to obviate many of the difficulties associated with translation of basic science findings. The Working Group urged a new focus on translational research that emphasizes efficacy and clinically relevant outcomes, and recommended the establishment of a system for rigorous preclinical testing of promising cardioprotective agents with clinical trial-like approaches (ie, blinded, randomized, multicenter, and adequately powered studies using standardized methods). A national preclinical research consortium would enable rational translation of important basic science findings into clinical use. The Working Group recommended that the National Institutes of Health proactively intervene to remedy current problems that impede translation of cardioprotective therapies. Their specific recommendations include the establishment of a preclinical consortium and the performance of 2 clinical studies that are likely to demonstrate effectiveness (phase III clinical trials of adenosine in acute myocardial infarction and cardiac surgery).
Key Words: basic science • myocardial ischemia • reperfusion injury • ischemic heart disease • cardiac surgery • cardioprotection • research translation
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|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 D. M. Yellon and D. J. Hausenloy Myocardial Reperfusion Injury N. Engl. J. Med., September 13, 2007; 357(11): 1121 - 1135. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
C. B. Granger and M. R. Patel The Search for Myocardial Protection: Is There Still Hope? J. Am. Coll. Cardiol., July 31, 2007; 50(5): 406 - 408. [Full Text] [PDF]
|
|
|
|
|
|
C. Dezfulian, N. Raat, S. Shiva, and M. T. Gladwin Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics Cardiovasc Res, July 15, 2007; 75(2): 327 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. E. Stansfield, N. C. Moss, M. S. Willis, R. Tang, and C. H. Selzman Proteasome Inhibition Attenuates Infarct Size and Preserves Cardiac Function in a Murine Model of Myocardial Ischemia-Reperfusion Injury Ann. Thorac. Surg., July 1, 2007; 84(1): 120 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Dirksen, G. J. Laarman, M. L. Simoons, and D. J.G.M. Duncker Reperfusion injury in humans: A review of clinical trials on reperfusion injury inhibitory strategies Cardiovasc Res, June 1, 2007; 74(3): 343 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lerman, D. R. Holmes, J. Herrmann, and B. J. Gersh Microcirculatory dysfunction in ST-elevation myocardial infarction: cause, consequence, or both? Eur. Heart J., April 1, 2007; 28(7): 788 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Wang, H. Fraser, S. G. Lloyd, J. J. McVeigh, L. Belardinelli, and J. C. Chatham A Comparison between Ranolazine and CVT-4325, a Novel Inhibitor of Fatty Acid Oxidation, on Cardiac Metabolism and Left Ventricular Function in Rat Isolated Perfused Heart during Ischemia and Reperfusion J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 213 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Wang, C. Zaragoza, and W. Holman Sodium-Hydrogen Exchange Inhibition and {beta}-Blockade Additively Decrease Infarct Size Ann. Thorac. Surg., March 1, 2007; 83(3): 1121 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. V. Pierre, C. Yang, Z. Yuan, J. Seminerio, C. Mouas, K. D. Garlid, P. Dos-Santos, and Z. Xie Ouabain triggers preconditioning through activation of the Na+,K+-ATPase signaling cascade in rat hearts Cardiovasc Res, February 1, 2007; 73(3): 488 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bolli Preconditioning: a paradigm shift in the biology of myocardial ischemia Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H19 - H27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Taylor, M. E. Olsen, and J. W. Starnes Improved postischemic function following acute exercise is not mediated by nitric oxide synthase in the rat heart Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H601 - H607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Doukas, W. Wrasidlo, G. Noronha, E. Dneprovskaia, R. Fine, S. Weis, J. Hood, A. DeMaria, R. Soll, and D. Cheresh Phosphoinositide 3-kinase {gamma}/{delta} inhibition limits infarct size after myocardial ischemia/reperfusion injury PNAS, December 26, 2006; 103(52): 19866 - 19871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E K Iliodromitis, S Kyrzopoulos, I A Paraskevaidis, K G Kolocassides, S Adamopoulos, G Karavolias, and D T Kremastinos Increased C reactive protein and cardiac enzyme levels after coronary stent implantation. Is there protection by remote ischaemic preconditioning? Heart, December 1, 2006; 92(12): 1821 - 1826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. W. Bar, D. Tzivoni, M. T. Dirksen, A. Fernandez-Ortiz, G. R. Heyndrickx, J. Brachmann, J. H.C. Reiber, N. Avasthy, J. Tatsuno, M. Davies, et al. Results of the first clinical study of adjunctive CAldaret (MCC-135) in patients undergoing primary percutaneous coronary intervention for ST-Elevation Myocardial Infarction: the randomized multicentre CASTEMI study Eur. Heart J., November 1, 2006; 27(21): 2516 - 2523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Theilmeier, C. Schmidt, J. Herrmann, P. Keul, M. Schafers, I. Herrgott, J. Mersmann, J. Larmann, S. Hermann, J. Stypmann, et al. High-Density Lipoproteins and Their Constituent, Sphingosine-1-Phosphate, Directly Protect the Heart Against Ischemia/Reperfusion Injury In Vivo via the S1P3 Lysophospholipid Receptor Circulation, September 26, 2006; 114(13): 1403 - 1409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. George, G.-H. Yi, A. R. Schulman, B. T. Morrow, Y. Cheng, A. Gu, G. Zhang, M. C. Oz, D. Burkhoff, and J. Wang A polymerized bovine hemoglobin oxygen carrier preserves regional myocardial function and reduces infarct size after acute myocardial ischemia Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1126 - H1137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Thuerauf, M. Marcinko, N. Gude, M. Rubio, M. A. Sussman, and C. C. Glembotski Activation of the Unfolded Protein Response in Infarcted Mouse Heart and Hypoxic Cultured Cardiac Myocytes Circ. Res., August 4, 2006; 99(3): 275 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Butler, L. C. Huffman, S. E. Koch, H. S. Hahn, and J. K. Gwathmey STAT-3 activation is necessary for ischemic preconditioning in hypertrophied myocardium Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H797 - H803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Takeda, M. Akao, M. Matsumoto-Ida, M. Kato, H. Takenaka, Y. Kihara, T. Kume, A. Akaike, and T. Kita Serofendic Acid, a Novel Substance Extracted From Fetal Calf Serum, Protects Against Oxidative Stress in Neonatal Rat Cardiac Myocytes J. Am. Coll. Cardiol., May 2, 2006; 47(9): 1882 - 1890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Zweier and M.A. H. Talukder The role of oxidants and free radicals in reperfusion injury Cardiovasc Res, May 1, 2006; 70(2): 181 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Li, Y. Guo, W. Tan, A. B. Stein, B. Dawn, W.-J. Wu, X. Zhu, X. Lu, X. Xu, T. Siddiqui, et al. Gene therapy with iNOS provides long-term protection against myocardial infarction without adverse functional consequences Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H584 - H589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bolli and A. Abdel-Latif No Pain, No Gain: The Useful Function of Angina Circulation, December 6, 2005; 112(23): 3541 - 3543. [Full Text] [PDF]
|
|
|
|
|
|
J. Tan, Z. Ma, L. Han, R. Du, L. Zhao, X. Wei, D. Hou, B. H. Johnstone, M. R. Farlow, and Y. Du Caffeic acid phenethyl ester possesses potent cardioprotective effects in a rabbit model of acute myocardial ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2265 - H2271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Davies, S. B. Digerness, C. R. Killingsworth, C. Zaragoza, C. R. Katholi, R. K. Justice, S. P. Goldberg, and W. L. Holman Multiple Treatment Approach to Limit Cardiac Ischemia-Reperfusion Injury Ann. Thorac. Surg., October 1, 2005; 80(4): 1408 - 1416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Juhaszova, C. Rabuel, D. B. Zorov, E. G. Lakatta, and S. J. Sollott Protection in the aged heart: preventing the heart-break of old age? Cardiovasc Res, May 1, 2005; 66(2): 233 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-C. Fan, X. Ren, J. Qian, Q. Yuan, P. Nicolaou, Y. Wang, W. K. Jones, G. Chu, and E. G. Kranias Novel Cardioprotective Role of a Small Heat-Shock Protein, Hsp20, Against Ischemia/Reperfusion Injury Circulation, April 12, 2005; 111(14): 1792 - 1799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Dawn, A. B. Stein, K. Urbanek, M. Rota, B. Whang, R. Rastaldo, D. Torella, X.-L. Tang, A. Rezazadeh, J. Kajstura, et al. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function PNAS, March 8, 2005; 102(10): 3766 - 3771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Karliner Symbols within words: Have we neglected the AdeNOsine A2 receptor? Cardiovasc Res, March 1, 2005; 65(4): 763 - 765. [Full Text] [PDF]
|
|