Abstract
The effect of preconditioning (PC) on acute ischemic myocardial injury was investigated in an openchest dog model. Preconditioned dogs received four 5-min occlusions of the left anterior descending coronary artery (LAD), each separated by 10 min of reperfusion. Four groups were used to assess the effect: non-PC group (G-1), PC group (G-2), 8-phenyltheophylline-(adenosine receptor blocker) infused PC group (G-3), and nicorandil- (ATP-sensitive K-channel opener) infused PC group (G-4). The LAD was occluded for 60 min, followed by 60 min of reperfusion in all dogs. The rate of ultrastructural myocardial severe injury was 26% in G-1, 0% in G-2, 5% in G-3, and 0% in G-4. Biochemical analayses also indicated higher values of myocardial contractile function in G-2 and G-4 than G-1 and G-3. These data suggest that the adenosine receptor and K channel may play a key role in PC.
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References
Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 75:1124–1136
Li GC, Vasquez JA, Gallagher KP, Lucchesi BR (1990) Myocardial protection with preconditioning. Circulation 82:609–619
Hoffmeister HM, Mauser M, Schaper W (1986) Repeated short periods of regional myocardial ischemia: effect on local function and high energy phosphate levels. Basic Res Cardiol 81:361–372
Gross GJ, Auchampach JA (1992) Blockade of ATP-sensitive potassium channels prevents myocardial preconditioning in dogs. Circ Res 70:223–233
Kitakaze M, Hori M, Takashima S, Sato H, Inoue M, Kamada T (1993) Ischemic preconditioning increases adenosine release and 5′-nucleotidase activity during myocardial ischemia and reperfusion in dogs: implication for myocardial salvage. Circulation 87:208–215
Yellon DM, Alkhulaifi AM, Browne EE, Pugsley WB (1992) Ischemic preconditioning limits infarct size in the rat heart. Cardiovasc Res 26:983–987
Cohen MV, Liu GS, Downey JM (1991) Preconditioning causes improved wall motion as well as smaller infarcts after transient coronary occlusion in rabbits. Circulation 84:341
Liu GS, Thornton J, Van Winkle DM, Stanley AWH, Olsson RA, Downey JM (1991) Protection against infarction afforded by preconditioning is mediated by A1-adenosine receptors in the rabbit heart. Circulation 84:350–356
Schott RJ, Rohmann S, Braun ER, Schaper W (1990) Ischemic preconditioning reduces infarct size in swine myocardium. Circ Res 66:1133–1142
Deutsch E, Berger M, Kussmaul WG, Hirshfeld JW, Herrmann HG, Laskey WK (1990) Adaptation to ischemia during percutaneous transluminal coronary angioplasty: clinical, hemodynamic, and metabolic features. Circulation 82:2044–2051
Yellon, DM, Alkhulaifi AM, Pugsley WB (1993) Preconditioning the human myocardium. Lancet 342:276–277
Kloner RA, Shook T, Przyklenk K, Davis VG, Cannon CP, McCabe CH, Braunwald E (1995) Previous angina alters inhospital outcome in TIMI 4: a Clinical correlate to preconditioning? Circulation 91:37–47
Murry CE, Richard VJ, Reimer KA, Jennings RB (1990) Ischemic preconditioning slows energy metabolism and delays ultrastructural damage during a sustained ischemic episode. Circ Res 66:913–931
Fox KAA, Saffitz JE, Corr PB (1987) Pathogenesis of myocardial reperfusion. Cardiol Clin 5:31–48
Virmani R, Forman MB, Kolodgie FD (1990) Myocardial reperfusion injury: histopathological effects of perfluorochemical. Circulation 81(suppl IV):57–68
Kloner RA, Ganote CE, Whalen DA, Jennings RB (1974) Effect of a transient period of ischemia on myocardial cells. II. Fine structure during the first few minutes of reflow. Am J Pathol 74:399–421
Kloner RA, Braunwald E (1980) Observations on experimental myocardial ischemia. Cardiovasc Res 14:371–395
Jennings RB, Ganote CE (1974) Structural changes in myocardium during acute ischemia. Circ Res 34, 35(suppl III):III-156–III-168
Ozawa K, Takeyama Y, Katagiri T (1982) Electron microscopic studies on the ATPase activity in myocardial infarction. Jpn Circ J 46:725–733
Konno N, Yanagishita T, Geshi E, Katagiri T (1987) Degradation of the cardiac sarcoplasmic reticulum in acute myocardial ischemia. Jpn Circ J 51:411–420
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T. Nature 227:680–685
Toba K, Katagiri T, Takeyama Y (1978) Studies on the cardiac sarcoplasmic reticulum in myocardial infarction. Jpn Circ J 42:447–453
Nakae I, Hashimoto K, Morigami N, Nakagawa M, Nakamura Y, Mitsunami K, Kinoshota M (1992) Mechanisms of action of nicorandil on coronary artery in dogs. Ther Res 13:1766
Nakae I, Quan L, Hashimoto K, Sugimoto Y, Tsutamoto Y, Kinoshota M (1994) Mechanism of the vasodilatory action of nicorandil on coronary circulation in dogs. Cardiovasc Drugs Ther 8:137–145
Hashimoto K, Kinoshota M, Ohbayashi Y (1991) Coronary effect of nicorandil in comparsion with nitroglycerin in chronic conscious dogs. Cardiovasc Drugs Ther 5:131–138
Geshi E, Konno N, Ito S, Mukae S, Suwa Y, Hiroshige J, Hasegawa S, Umetsu K, Mochizuki T, Kitsu T, Yanagishita T, Tanno F, Yaida M, Sekita S, Katagiri T (1989) Pharmacological intervention of acute ischemic myocardial injury. J Mol Cell Cardiol Suppl 21:S139
Hearse DJ (1995) Activation of ATP-sensitive potassium channels: a novel pharmacological approch to myocardial protection? Cardiovasc Res 30:1–17
Nakae I, Quan L, Sugimoto Y, Tsutamoto Y, Kinoshota M (1994) Glibenclamide-induced oscillation of canine coronary artery is independent of myocardial ischemia. J Cardiovasc Pharmacol 23:473–479
George CL, Juan AV, Kim PG, Benedict RL (1995) Myocardial protection with preconditionung. Circulation 82:609–619
Menasche P, Kevelaitis E, Mouas C, Grousset C, Piwnica A, Bloch G (1995) Preconditioning with potassium channel openers. J Cardiovasc Surg 110:1606–1613
Hagar JM, Hale SL, Kloner RA (1991) Effect of preconditioning ischemia on reperfusion arrhythmias after coronary artery occlusion and reperfusion in the rat. Circ Res 68:61–68
Vegh A, Komori S, Szekeres L, Parratt JR (1992) Antiarrhythmic effects of preconditioning in anesthetised dogs and rats. Cardiovasc Res 26:487–495
Tan HL, Mazon P, Verberne HJ, Sleeswijk, ME, Coronel R, Opthof T, Janse MJ (1993) Ischemic preconditioning delays ischema-induced cellular electrical uncoupling in rabbit myocardium by activation of ATP-sensitive potassium channels. Cardiovasc Res 27:644–651
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Nakatani, M., Ishioka, H., Koba, S. et al. Ultrastructural and biochemical studies of ischemic preconditioning using an adenosine receptor blocker and an ATP-sensitive K channel opener. Med Electron Microsc 30, 63–69 (1997). https://doi.org/10.1007/BF01545083
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DOI: https://doi.org/10.1007/BF01545083