Summary
Ischemic preconditioning renders the myocardium resistant to a subsequent sustained ischemic insult. The aim of this study was to investigate whether the reoxygenation that occurs during the intervening reperfusion of ischemic preconditioning is required for the development of cardioprotection. Isolated perfused rat hearts were either non-preconditioned (CONT) or preconditioned by 5 min ischemia and 5 min normoxic (IPCN) or hypoxic (IPCH) reperfusion before being subjected to 30 min total global normothermic ischemia followed by 30 min normoxic reperfusion. IPCN did not significantly alter the pre-ischemic status of tissue metabolites. However, after IPCH, ATP and glycogen levels were depressed and lactate content increased. As expected, IPCN protected the myocardium in terms of post-ischemic functional recovery (LVDP: IPCN = 53 ± 3% vs CONT = 31 ± 4%; p < 0.01). IPCH also improved contractile recovery (LVDP: 71 ± 5%, p < 0.01 vs CONT) and its cardioprotective effect was higher than that of IPCN (p < 0.05). At the end of reperfusion, tissue metabolite levels were not significantly different between IPCN and CONT groups while in IPCH group ATP level was significantly higher and AMP level was lower (p < 0.05 vs CONT). Our results show that i) during the intervening reperfusion of ischemic preconditioning, reoxygenation is not mandatory to achieve cardioprotection, and ii) a transient hypoxic reperfusion further enhances the beneficial effects of preconditioning against post-ischemic contractile dysfunction. We suggest that this latter phenomenon might be, at least in part, the consequence of glycogen depletion induced by the transient hypoxic reperfusion.
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References
Murry C, Jennings R, Reimer K. 1986. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136.
Liu G, Thornton J, Van Winkle D, Stanley A, Olsson R, Downey JM. 1991. Protection against infarction afforded by preconditioning is mediated by Al adenosine receptors in rabbit heart. Circulation 84:350–356.
Schott R, Rohmann S, Braun E, Schaper W. 1989. Ischemic preconditioning reduces infarct size in swine myocardium. Circ Res 66:1133–1142.
Yellon D, Alkhulaifi A, Browne E, Pugsley W 1992. Ischaemic preconditioning limits infarct size in the rat heart. Cardiovasc Res 26:983–987.
Jennings R, Pugsley W, Yellon D. 1995. Ischemic preconditioning in model of global ischemia: infarct size limitation but no reduction of stunning. J Mol Cell Cardiol 27:1623–1632.
Mei D, Nithipatikom K, Lasley R, Gross G. 1998. Myocardial preconditioning produced by ischemia, hypoxia and a KATP channel opener: effects on interstitial adenosine in dogs. J Mol Cell Cardiol 30:1225–1236.
Simkhovich B, Przyklenk K, Kloner R. 1998. Role of protein kinase C as a cellular mediator of ischemic preconditioning: a critical review. Cardiovasc Res 40:9–22.
Wolfe C, Sievers R, Visseren F, Donnelly T 1993. Loss of myocardial protection after preconditioning correlates with the time course of glycogen recovery within the preconditioning segment. Circulation 87:881–892.
Ambrosio G, Tritto I, Chiariello M. 1995. The role of oxygen free radicals in preconditioning. J Mol Cell Cardiol 27:1035–1039.
Murry C, Richard V, Jennings R, Reimer K. 1988. Preconditioning with ischemia: is the protective effect mediated by free radical-induced myocardial stunning? Circulation 78(II):77 (Abstract).
Bolli R. 1991. Oxygen-derived free radicals and myocardial reperfusion injury: an overview. Cardiovasc Drugs Ther 5(2):249–268.
Osada M, Takeda S, Sato T, Komori S, Tamura K. 1994. The protective effect of preconditioning on reperfusion-induced arrhythmia is lost by treatment with superoxide dismutase. Jpn Circ J 58:259–263.
Gutmann I, Wahlefeld AW 1974. L-(+)-lactate determination with lactate dehydrogenase and NAD. In: Methods of enzymatic analysis. Ed. HU Bergmeyer, 1464–1475. New York: Academic Press.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. 1951. Protein measurement with the Folin reagents. J Biol Chem 193:265–275.
Reimer K, Murry C, Yamasawa I, Hill M, Jennings R. 1986. Four brief periods of ischaemia cause no cumulative ATP loss or necrosis. Am J Physiol 251.H1306–H1315.
Dekker L. 1998. Toward the heart of ischemic preconditioning. Cardiovasc Res 37:14–20.
Ferdinandy P, Szilvassy Z, Baxter G. 1998. Adaptation to myocardial stress in disease states: is preconditioning a healthy heart phenomenon? TIPS 19:223–229.
Murry C, Richard V, Jennings R, Reimer K. 1991. Myocardial protection is lost before contractile function recovers from ischemic preconditioning. Am J Physiol 260:H796–H804.
Yellon D, Baxter G. 1995. A “second window of protection” or delayed preconditioning phenomenon: future horizons for myocardial protection? J Mol Cell Cardiol 27:1023–1034.
Ovize M, Przyklenk K, Kloner R. 1992. Partial coronary stenosis is sufficient and complete reperfusion is mandatory for preconditioning the canine heart. Circ Res 71:1165–1173.
Hoffmeister H, Ströbele M, Bäler A, Kazmaier, Seipel L. 1998. Preconditioning preserves energy metabolism in prolonged low-flow ischemia. Basic Res Cardiol 93:487–493.
Schultz R, Post H, Sakka S, Wallbridge D, Heusch G. 1995. Intraischemic preconditioning. Increased tolerance to sustained low-flow ischemia by a brief no-flow ischemia without intermittent reperfusion. Circ Res 76:942–950.
Tanaka M, Fujiwara H, Yamasaki K, Sasayama S. 1994. Superoxide dismutase and N-2-mercaptopropionyl glycine attenuate infarct size Hmitation effect of ischaemic preconditioning in the rabbit. Cardiovasc Res 28:980–986.
Tritto I, D’Andrea D, Eramo N, Scognamiglio A, De Simone C, Violante A, Esposito A, Chiariello M, Ambrosio G. 1997. Oxygen radicals can induce preconditioning in rabbit hearts. Circ Res 80:743–748.
Baines C, Goto M, Downey J. 1997. Oxygen radicals released during ischemic preconditioning contribute to cardioprotection in the rabbit myocardium. J Mol Cell Cardiol 29:207–216.
Iwamoto T, Miura T, Adashi T, Noto T, Ogawa T, Tsuchida A, Iimura O. 1991. Myocardial infarct size-limiting effect of ischemic preconditioning was not attenuated by free-radical scavengers in the rabbit. Circulation 83:1015–1022.
Richard V, Tron C, Thuillez C. 1993. Ischaemic preconditioning is not mediated by oxygen derived free radicals in rats. Cardiovasc Res 27:2016–2021.
Vanden Hoek T, Becker L, Shao Z, Li C, Schumacker P. 1998. Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes. J Biol Chem 273:1892–1898.
Arad M, de Jong J, de Jonge R, Huizer T, Rabinowitz B. 1996. Preconditioning in globally ischemic isolated rat hearts: effect on function and metabolic indices of myocardial damage. J Mol Cell Cardiol 28:2479–2490.
de Albuquerque C, Gerstenblith G, Weiss R. 1994. Importance of metabolic inhibition and cellular pH in mediating preconditioning contractile and metabolic effects in rat hearts. Circ Res 74:139–150.
Doenst T, Guthrie P, Taegmeyer H. 1998. Ischemic preconditioning in rat heart: no correlation between glycogen content and return of function. Mol Cel Biochem 180:153–161.
Neely J, Grotyohann L. 1984. Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts. Circ Res 55:816–824.
Dobson J, Mayer S. 1975. Mechanisms of activation of cardiac glycogen Phosphorylase in ischemia and anoxia. Circ Res 33:412–420.
King L, Opie L. 1996. Does preconditioning act by glycogen depletion in the isolated rat heart? J Mol Cell Cardiol 28:2305–2321.
Gorman M, He M-X, Sparks H. 1994. Adenosine formation during hypoxia in isolated hearts: effect of adrenergic blockade. J Mol Cell Cardiol 26:1613–1623.
Li Y, Kloner R. 1993. The cardioprotective effects of ischemic “preconditioning” are not mediated by adenosine receptors in rat hearts. Circulation 87:1642–1648.
Bunger R, Soboll S. 1986. Cytosolic adenylates and adenosine release in perfused working heart. Eur J Biochem 159:203–213.
Darvish A, Metting P. 1993. Purification and regulation of an AMP-specific cytosolic 5′-nucleotidase from dog heart. Am J Physiol 264:H1529–H1534.
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Toufektsian, MC., Tanguy, S., Morel, S., Benajiba, N., Boucher, F., de Leiris, J. (2003). Hypoxic Reperfusion after Brief Ischemia Potentiates Ischemic Preconditioning in Isolated Rat Hearts. In: Dhalla, N.S., Takeda, N., Singh, M., Lukas, A. (eds) Myocardial Ischemia and Preconditioning. Progress in Experimental Cardiology, vol 6. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0355-2_16
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DOI: https://doi.org/10.1007/978-1-4615-0355-2_16
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