Does reperfusion injury exist in humans?

Heart Institute, Hospital of the Good Samaritan, Los Angeles, California 90017-2395.

Timely coronary reperfusion as treatment for acute myocardial infarction reduces myocardial infarct size, improves left ventricular function and survival. There is still concern that at the time of reperfusion, a further injury occurs to the myocardium. Theoretically, if this "reperfusion injury" could be treated and eliminated, the outcome for patients with myocardial infarction might further improve. The concept of reperfusion injury is closely tied to the concept that oxygen radicals generated at the time of reperfusion cause tissue damage. There are four basic forms of reperfusion injury. Lethal reperfusion injury is described as myocyte cell death due to reperfusion itself rather than to the preceding ischemia. This concept continues to be controversial in both experimental animal and clinical studies. Vascular reperfusion injury refers to progressive damage to the vasculature over time during the phase of reperfusion. Manifestations of vascular reperfusion injury include an expanding zone of no reflow and a deterioration of coronary flow reserve. This form of reperfusion injury has been documented in animal models and probably occurs in humans. Stunned myocardium refers to postischemic ventricular dysfunction of viable myocytes and probably represents a form of "functional reperfusion injury." This phenomenon is well documented in both animal models and humans. Reperfusion arrhythmias represent the fourth form of reperfusion injury. They include ventricular tachycardia and fibrillation that occur within seconds to minutes of restoration of coronary flow after brief (5 to 15 min) episodes of myocardial ischemia. True reperfusion arrhythmias occur in only a small percentage of patients receiving thrombolytic therapy for acute myocardial infarction and are not a sensitive indicator for successful reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

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				H.M. Piper, D. Garcna-Dorado, and M. Ovize A fresh look at reperfusion injury Cardiovasc Res, May 1, 1998; 38(2): 291 - 300. [Full Text] [PDF]

				C. P. Murrah, E. R. Ferguson, R. D. Spruell, and W. L. Holman Arrest Duration Influences Postcardioplegia Electrophysiologic Recovery and Reperfusion Arrhythmias Ann. Thorac. Surg., April 1, 1998; 65(4): 1003 - 1008. [Abstract] [Full Text] [PDF]

				N. Delanty, M.P. Reilly, D. Pratico, J.A. Lawson, J.F. McCarthy, A.E. Wood, S.T. Ohnishi, D.J. Fitzgerald, and G.A. FitzGerald 8-Epi PGF2{alpha} Generation During Coronary Reperfusion: A Potential Quantitative Marker of Oxidant Stress In Vivo Circulation, June 3, 1997; 95(11): 2492 - 2499. [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]

				A. Saraste, K. Pulkki, M. Kallajoki, K. Henriksen, M. Parvinen, and L.-M. Voipio-Pulkki Apoptosis in Human Acute Myocardial Infarction Circulation, January 21, 1997; 95(2): 320 - 323. [Abstract] [Full Text]

				G. Ambrosio, S. Betocchi, L. Pace, M. A. Losi, P. Perrone-Filardi, A. Soricelli, F. Piscione, J. Taube, F. Squame, M. Salvatore, et al. Prolonged Impairment of Regional Contractile Function After Resolution of Exercise-Induced Angina: Evidence of Myocardial Stunning in Patients With Coronary Artery Disease Circulation, November 15, 1996; 94(10): 2455 - 2464. [Abstract] [Full Text]

				R. H. Chen The Scientific Basis for Hypocalcemic Cardioplegia and Reperfusion in Cardiac Surgery Ann. Thorac. Surg., September 1, 1996; 62(3): 910 - 914. [Abstract] [Full Text]

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				E. M. Antman Magnesium in Acute MI : Timing Is Critical Circulation, November 1, 1995; 92(9): 2367 - 2372. [Full Text]

				F.-J. Neumann, I. Ott, M. Gawaz, G. Richardt, H. Holzapfel, M. Jochum, and A. Schomig Cardiac Release of Cytokines and Inflammatory Responses in Acute Myocardial Infarction Circulation, August 15, 1995; 92(4): 748 - 755. [Abstract] [Full Text]

				Y. Ohnishi, M. C. Butterfield, J. E. Saffitz, B. E. Sobel, P. B. Corr, and J. A. Goldstein Deleterious Effects of a Systemic Lytic State on Reperfused Myocardium : Minimization of Reperfusion Injury and Enhanced Recovery of Myocardial Function by Direct Angioplasty Circulation, August 1, 1995; 92(3): 500 - 510. [Abstract] [Full Text]

				D. Zahger, J. Yano, A. Chaux, M. C. Fishbein, and W. Ganz Absence of Lethal Reperfusion Injury After 3 Hours of Reperfusion : A Study in a Single-Canine-Heart Model of Ischemia-Reperfusion Circulation, June 15, 1995; 91(12): 2989 - 2994. [Abstract] [Full Text]