Does ischemic preconditioning occur in patients?

Heart Institute Research Laboratory, Hospital of the Good Samaritan, University of Southern California, Los Angeles 90017.

Ischemic preconditioning offers powerful protection from ischemic necrosis in a wide range of animal species, but does it occur in humans? Support for preconditioning in humans comes from several sources: studies showing increased tolerance to repetitive balloon inflations during angioplasty, some (but not all) studies suggesting that preinfarction angina confers an early beneficial effect, studies showing that patients can develop sudden tolerance to repetitive exercise- or pacing-induced ischemia, cardiothoracic studies of intermittent aortic cross-clamping showing better preservation of myocardial adenosine triphosphate and in vitro studies of isolated human trabecular muscle and isolated human ventricular myocytes that demonstrate a biology consistent with preconditioning. In the future, preconditioning or "preconditioning mimetic" agents have the potential to be applied to a wide array of cardiovascular disorders and might result in better preservation of the heart in instances of cardiopulmonary bypass, heart transplantation, angina and myocardial infarction.

This article has been cited by other articles:

				E. B. Savage, R. S. Farivar, and E. J. Okum Cardiac Surgical Physiology Card. Surg. Adult, January 1, 2008; 3(2008): 51 - 76. [Full Text]

				R. A. Kloner Moving Preconditioning From Bench to Bedside J. Am. Coll. Cardiol., July 4, 2006; 48(1): 215 - 216. [Full Text] [PDF]

				W. K. Laskey, P. Staat, G. Rioufol, E. Bonnefoy, G. Finet, X. Andre-Fouet, M. Ovize, C. Piot, T. T. Cung, Y. Cottin, et al. Letter Regarding Article by Staat et al, "Postconditioning the Human Heart" Circulation, March 28, 2006; 113(12): e665 - e665. [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]

				R. A. Kloner and B. Z. Simkhovich Benefit of an exercise program before myocardial infarction J. Am. Coll. Cardiol., March 15, 2005; 45(6): 939 - 940. [Full Text] [PDF]

				S. Vogt, I. Portig, B. Kusch, S. Pankuweit, A. S. Sirat, D. Troitzsch, B. Maisch, and R. Moosdorf Detection of anti-hsp70 immunoglobulin G antibodies indicates better outcome in coronary artery bypass grafting patients suffering from severe preoperative angina Ann. Thorac. Surg., September 1, 2004; 78(3): 883 - 889. [Abstract] [Full Text] [PDF]

				W. K. Laskey and D. Beach Frequency and clinical significance of ischemic preconditioning during percutaneous coronary intervention J. Am. Coll. Cardiol., September 17, 2003; 42(6): 998 - 1003. [Abstract] [Full Text] [PDF]

				J. F. Huizar, L. A. Gonzalez, J. Alderman, and H. S. Smith Sulfonylureas attenuate electrocardiographic ST-segment elevation during an acute myocardial infarction in diabetics J. Am. Coll. Cardiol., September 17, 2003; 42(6): 1017 - 1021. [Abstract] [Full Text] [PDF]

				Y Birnbaum and B J Drew The electrocardiogram in ST elevation acute myocardial infarction: correlation with coronary anatomy and prognosis Postgrad. Med. J., September 1, 2003; 79(935): 490 - 504. [Abstract] [Full Text]

				M. C. Riddle Sulfonylureas Differ in Effects on Ischemic Preconditioning--Is it Time to Retire Glyburide? J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 528 - 530. [Full Text] [PDF]

				J. Vinten-Johansen, Z.-Q. Zhao, and R. A. Guyton Cardiac Surgical Physiology Card. Surg. Adult, January 1, 2003; 2(2003): 53 - 84. [Full Text]

				R. Scognamiglio, A. Avogaro, S. Vigili de Kreutzenberg, C. Negut, M. Palisi, E. Bagolin, and A. Tiengo Effects of Treatment With Sulfonylurea Drugs or Insulin on Ischemia-Induced Myocardial Dysfunction in Type 2 Diabetes Diabetes, March 1, 2002; 51(3): 808 - 812. [Abstract] [Full Text] [PDF]

				R. A. Kloner and R. B. Jennings Consequences of Brief Ischemia: Stunning, Preconditioning, and Their Clinical Implications: Part 2 Circulation, December 18, 2001; 104(25): 3158 - 3167. [Abstract] [Full Text] [PDF]

				K. Nandagopal, T. M. Dawson, and V. L. Dawson Critical Role for Nitric Oxide Signaling in Cardiac and Neuronal Ischemic Preconditioning and Tolerance J. Pharmacol. Exp. Ther., April 12, 2001; 297(2): 474 - 478. [Abstract] [Full Text]

				T. Sato, N. Sasaki, B. O'Rourke, and E. Marban Adenosine Primes the Opening of Mitochondrial ATP-Sensitive Potassium Channels : A Key Step in Ischemic Preconditioning? Circulation, August 15, 2000; 102(7): 800 - 805. [Abstract] [Full Text] [PDF]

				T. Sato, N. Sasaki, B. O'Rourke, and E. Marban Nicorandil, a potent cardioprotective agent, acts by opening mitochondrial ATP-dependent potassium channels J. Am. Coll. Cardiol., February 1, 2000; 35(2): 514 - 518. [Abstract] [Full Text] [PDF]

				D Karila-Cohen, D Czitrom, E Brochet, M Faraggi, P Seknadji, D Himbert, J.-M Juliard, P Assayag, and P.G Steg Decreased no-reflow in patients with anterior myocardial infarction and pre-infarction angina Eur. Heart J., December 1, 1999; 20(23): 1724 - 1730. [Abstract] [PDF]

				C.-H. Chen, M. O. Gray, and D. Mochly-Rosen Cardioprotection from ischemia by a brief exposure to physiological levels of ethanol: Role of epsilon protein kinase C PNAS, October 26, 1999; 96(22): 12784 - 12789. [Abstract] [Full Text] [PDF]

				G. W. Dorn II, M. C. Souroujon, T. Liron, C.-H. Chen, M. O. Gray, H. Z. Zhou, M. Csukai, G. Wu, J. N. Lorenz, and D. Mochly-Rosen Sustained in vivo cardiac protection by a rationally designed peptide that causes varepsilon protein kinase C translocation PNAS, October 26, 1999; 96(22): 12798 - 12803. [Abstract] [Full Text] [PDF]

				M. A. Leesar, M. F. Stoddard, S. Manchikalapudi, and R. Bolli Bradykinin-induced preconditioning in patients undergoing coronary angioplasty J. Am. Coll. Cardiol., September 1, 1999; 34(3): 639 - 650. [Abstract] [Full Text] [PDF]

				W. K. Laskey Beneficial Impact of Preconditioning During PTCA on Creatine Kinase Release Circulation, April 27, 1999; 99(16): 2085 - 2089. [Abstract] [Full Text] [PDF]

				M. Billinger, M. Fleisch, F. R. Eberli, A. Garachemani, B. Meier, and C. Seiler Is the development of myocardial tolerance to repeated ischemia in humans due to preconditioning or to collateral recruitment? J. Am. Coll. Cardiol., March 15, 1999; 33(4): 1027 - 1035. [Abstract] [Full Text] [PDF]

				H. Klepzig, G. Kober, C. Matter, H. Luus, H. Schneider, K.H. Boedeker, W. Kiowski, F.W. Amann, D. Gruber, S. Harris, et al. Sulfonylureas and ischaemic preconditioning; a double-blind, placebo-controlled evaluation of glimepiride and glibenclamide Eur. Heart J., March 2, 1999; 20(6): 439 - 446. [Abstract] [PDF]

				K.F. Fox, M.R. Cowie, D.A. Wood, A.J.S. Coats, P.A. Poole-Wilson, and G.C. Sutton New perspectives on heart failure due to myocardial ischaemia Eur. Heart J., February 2, 1999; 20(4): 256 - 262. [PDF]

				R. H. Christenson and H. M. E. Azzazy Biochemical markers of the acute coronary syndromes Clin. Chem., August 1, 1998; 44(8): 1855 - 1864. [Abstract] [Full Text] [PDF]

				R. A. Kloner, R. Bolli, E. Marban, L. Reinlib, and E. Braunwald Medical and Cellular Implications of Stunning, Hibernation, and Preconditioning : An NHLBI Workshop Circulation, May 19, 1998; 97(18): 1848 - 1867. [Full Text] [PDF]

				R. A. Kloner, T. Shook, E. M. Antman, C. P. Cannon, K. Przyklenk, K. Yoo, C. H. McCabe, and E. Braunwald Prospective Temporal Analysis of the Onset of Preinfarction Angina Versus Outcome : An Ancillary Study in TIMI-9B Circulation, March 24, 1998; 97(11): 1042 - 1045. [Abstract] [Full Text] [PDF]

				E. R. Schwarz, J. Fleischhauer, H. Montino, R. Chakupurakal, M. Foresti, T. Schuetz, S. Sack, M. Mohri, M. Arras, W. Schaper, et al. Infarct Size Reduction by Ischemic Preconditioning is a Monophasic, Short-Lived Phenomenon in Anesthetized Pigs Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1998; 3(1): 63 - 70. [Abstract] [PDF]

				Y. Birnbaum, S. L. Hale, and R. A. Kloner Ischemic Preconditioning at a Distance : Reduction of Myocardial Infarct Size by Partial Reduction of Blood Supply Combined With Rapid Stimulation of the Gastrocnemius Muscle in the Rabbit Circulation, September 2, 1997; 96(5): 1641 - 1646. [Abstract] [Full Text]

				R. A. Kloner and G. Kay EDITORIAL: INTRAVENOUS CO-INFUSION OF ADENOSINE AND NOREPINEPHRINE J. Thorac. Cardiovasc. Surg., August 1, 1997; 114(2): 234 - 235. [Full Text]

				M. Tani, Y. Suganuma, H. Hasegawa, K. Shinmura, Y. Hayashi, X.-d. Guo, and Y. Nakamura Changes in Ischemic Tolerance and Effects of Ischemic Preconditioning in Middle-aged Rat Hearts Circulation, June 3, 1997; 95(11): 2559 - 2566. [Abstract] [Full Text]

				P. K. Kaukoranta, M. P. K. Lepojarvi, K. V. Ylitalo, K. T. Kiviluoma, and K. J. Peuhkurinen Normothermic Retrograde Blood Cardioplegia With or Without Preceding Ischemic Preconditioning Ann. Thorac. Surg., May 1, 1997; 63(5): 1268 - 1274. [Abstract] [Full Text]

				S. J. Kapadia, J. S. Terlato, and A. S. Most Presence of a Critical Coronary Artery Stenosis Does Not Abolish the Protective Effect of Ischemic Preconditioning Circulation, March 4, 1997; 95(5): 1286 - 1292. [Abstract] [Full Text]

				B. C.G. Gho, R. G. Schoemaker, M. A. van den Doel, D. J. Duncker, and P. D. Verdouw Myocardial Protection by Brief Ischemia in Noncardiac Tissue Circulation, November 1, 1996; 94(9): 2193 - 2200. [Abstract] [Full Text]

				V. Pasceri, G. A. Lanza, G. Patti, P. Pedrotti, F. Crea, and A. Maseri Preconditioning by Transient Myocardial Ischemia Confers Protection Against Ischemia-Induced Ventricular Arrhythmias in Variant Angina Circulation, October 15, 1996; 94(8): 1850 - 1856. [Abstract] [Full Text]

				Y. Birnbaum, K. Przyklenk, and R. A. Kloner Time Frame of Ischemic Preconditioning: Is It Clinically Relevant? Journal of Cardiovascular Pharmacology and Therapeutics, October 1, 1996; 1(4): 339 - 346. [PDF]

				A. K. Ganjoo and W. D. Johnson Cardioprotective effects of ischemic preconditioning J. Thorac. Cardiovasc. Surg., July 1, 1996; 112(1): 208 - 208. [Full Text]

				P. G. Burns, I. B. Krukenkamp, C. A. Caldarone, R. J. Kirvaitis, G. R. Gaudette, and S. Levitsky Is the Preconditioning Response Conserved in Senescent Myocardium? Ann. Thorac. Surg., March 1, 1996; 61(3): 925 - 929. [Abstract] [Full Text]

				K. Hu, D. Duan, G.-R. Li, and S. Nattel Protein Kinase C Activates ATP-Sensitive K+ Current in Human and Rabbit Ventricular Myocytes Circ. Res., March 1, 1996; 78(3): 492 - 498. [Abstract] [Full Text]

				F. Andreotti, V. Pasceri, D. R. Hackett, G. J. Davies, A. W. Haider, and A. Maseri Preinfarction Angina as a Predictor of More Rapid Coronary Thrombolysis in Patients with Acute Myocardial Infarction N. Engl. J. Med., January 4, 1996; 334(1): 7 - 12. [Abstract] [Full Text] [PDF]

				P. G. Burns, I. B. Krukenkamp, C. A. Caldarone, G. R. Gaudette, E. A. Bukhari, and S. Levitsky Does Cardiopulmonary Bypass Alone Elicit Myoprotective Preconditioning? Circulation, November 1, 1995; 92(9): 447 - 451. [Abstract] [Full Text]

				D. K. Arrell, I. Neverova, H. Fraser, E. Marban, and J. E. Van Eyk Proteomic Analysis of Pharmacologically Preconditioned Cardiomyocytes Reveals Novel Phosphorylation of Myosin Light Chain 1 Circ. Res., September 14, 2001; 89(6): 480 - 487. [Abstract] [Full Text] [PDF]