Abstract
Cardiac ischemia causes a rapid decline in mechanical performance and, if prolonged, myocardial cell death occurs on reperfusion. The early decline in mechanical performance could, in principle, be caused either by reduced intracellular calcium release or by reduced responsiveness of the myofibrillar proteins to calcium. It is now known that intracellular calcium rises during ischemia and that the early decline in mechanical performance is caused largely by the inhibitory effects of phosphate and protons on the myofibrillar proteins. The rise of intracellular calcium during ischemia is related to the acidosis and is probably caused by calcium influx on the Na/Ca exchanger. This is triggered by a rise in intracellular sodium which enter the cell in exchange for protons on the Na/H exchanger. Intracellular calcium rises still further on reperfusion and the elevation of calcium and the degree of muscle damage are closely correlated.
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References
Cooley DA, Reul J, Wukash DC. Ischemic contracture of the heart: stone heart. Am J Cardiol 1972; 29: 575–577.
Shen AC, Jennings RB. Myocardial calcium and magnesium in acute ischemic injury. Am J Path 1972; 67: 417–440.
Tani M. Mechanisms of Ca2+ overload in reperfused ischemic myocardium. Ann Rev Physiol 1990; 52: 543–559.
Lee JA, Allen DG. Mechanisms of acute ischemic contractile failure of the heart: role of intracellular calcium. J Clin Inves 1991; 88: 361–367.
Kleber AG, Oetliker H. Cellular aspects of early contractile failure in ischemia. In: Fozzard HA, et al (eds) The Heart and Cardiovascular System; 2nd Ed.; Raven Press, New York, 1992.
Kusuoka H, Marban E. Cellular mechanisms of myocardial stunning. Ann Rev Physiol 1992; 54: 243–256.
Janse MJ, Wit AL. Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol Rev 1989; 69: 1049–1169.
Katz AM, Hecht HH. The early “pump” failure of the ischemic heart. Am J Med 1969; 47: 497–502.
Fabiato A, Fabiato F. Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiac and skeletal muscles. J Physiol (Lond) 1978; 276: 233–255.
Jacobus WE, Pores IH, Lucas SK, Kallman CH, Weisfeldt ML, Flaherty IT. The role of intrcellular pH in the control of normal and ischemic myocardial contractility: a 31P nuclear magnetic resonance and mass spectroscopy study. In Nuccitelli R, Deamer DW (eds): Intracellular pH: Its Measurement, Regulation and Utilisation in Cellular Function, New York, Alan R Liss Inc, 1982.
Elliott AC, Smith GL, Eisner DA, Allen DG. Metabolic changes during ischemia and their role in contractile failure in isolated ferret hearts. J Physiol (Lond) 1992; 454: 467–490.
Koretsune Y, Corretti M, Kusuoka H, Marban E. Mechanism of early ischemic contractile failure: inexitability, metabolite accumulation or vascular collapse? Circ Res 1991; 68: 255–262.
Godt RE, Nosek TM. Changes of intracellular milieu with fatigue or hypoxia depress contraction of skinned rabbit skeletal and cardiac muscle. J Physiol (Lond) 1989; 412: 155–180.
Kentish JC. The effects of inorganic phosphate and creatine phosphate on force production in skinned muscles from rat ventricle. J Physiol (Lond) 1986; 370: 585–604.
Kitakaze M, Marban E. Cellular mechanism of the modulation of contractile function by coronary perfusion pressure in ferret hearts. J Physiol (Lond) 1989; 414: 455–472.
Steenbergen C, Murphy E, Levy L, London RE. Elevation in cytosolic free Ca concentration early in myocardial ischemia in perfused rat heart. Circ Res 1987; 60: 700–707.
Lee H-C, Mohabir R, Smith N, Franz MR, Clusin WT. Effect of ischemia on Ca-dependent fluorescence transients in rabbit hearts containing indo-1. Circulation 1988; 78: 1047–1059.
Kihara Y, Grossman W, Morgan JP. Direct measurement of changes in intracellular Ca transients during hypoxia, ischemia and reperfusion of the intact mammalian heart. Circ Res 1989; 65: 1029–1044.
Allen DG, Lee JA, Smith GL. The consequences of simulated ischemia on intracellular Ca2+ and tension in isolated ferret ventricular muscle. J Physiol (Lond) 1989; 410: 297–323.
Lee JA, Allen DG. Changes in intracellular free calcium concentration during long exposures to simulated ischemia in isolated mammalian ventricular muscle. Circ Res 1992; 71: 58–69.
Smith GL, Allen DG. The effects of metabolic blockade on intracellular calcium concentration in isolated ferret ventricular muscle. Circ Res 1988; 62: 1223–1236.
Tani M, Neely JR. Role of intracellular Na+ in Ca2+ overload and depressed recovery of ventricular function of reperfused ischemic rat hearts. Possible involvement of H+-Ca2+ and Na+-Ca2+ exchange. Circ Res 1990; 65: 1045–1056.
Thandroyen FT, McCarthy J, Burton KP, Opie LH. Ryanodine and caffeine prevent ventricular arrhythmias during acute myocardial ischemia and reperfusion in rat heart. Circ Res 1988; 62: 306–314.
Deitmer JW, Ellis D. Interactions between the regulation of the intracellular pH and sodium activity of sheep cardiac Purkinje fibres. J Physiol (Lond) 1980; 304: 471–488.
Allen DG, Eisner DA, Orchard CH. Factors influencing free intracellular calcium concentration in quiescent ferret ventricular muscle. J Physiol (Lond) 1984; 350: 615–630.
Cairns SP, Westerblad H, Allen DG. Changes of myoplasmic pH and calcium concentration during exposure to lactate in isolated rat ventricular myocytes. J Physiol (Lond) 1993 (in press).
De Hemptine A, Marrannes R, Vanheel B. Influence of organic acids on intracellular pH. Am J Physiol 1983; 245: C178–C183.
Kleyman TR, Cragoe EJ Jr. Amiloride and its analogs as tools in the study of ion transport. J Memb Biol 1988; 105: 1–21.
Minta A, Tsien RY. Fluorescent indicators for cytosolic sodium. J Biol Chem 1989; 264: 19449–19457.
Murphy E, Perlman M, London RE, Steenbergen C. Amiloride delays the ischemia-induced rise in cytosolic free calcium. Circ Res 1991; 68: 1250–1258.
Pike MM, Kitakaze M, Marban E. 23Na-NMR measurements of intracellular sodium in intact perfused ferret hearts during ischemia and reperfusion. Am J Physiol 1990; 259: H1767–H1773.
Wilde AAM, Kleber AG. the combined effects of hypoxia, high K+, and acidosis on the intracellular sodium activity and resting potential in guinea pig papillary muscle. Circ Res 1986; 58: 249–256.
Vanheel B, De Hemptine A, Leusen I. Acidification and intracellular sodium ion activity during simulated myocardial ischemia. Am J Physiol 1990; 259: C169–C179.
Lazdunski M, Frelin C, Vigne P. The sodium/hydrogen exchange system in cardiac cells: its biochemical and pharmacological properties and its role in regulating internal concentrations of sodium and internal pH. J Mol Cell Cardiol 1985; 17: 1029–1042.
Vaughan-Jones RD, Wu M-L. Extracellular H+ inactivation of Na+-H+ exchange in the sheep cardiac Purkinje fibre. J Physiol (Lond) 428: 441–466.
Kaila K, Vaughan-Jones RD. Influence of sodium-hydrogen exchange on intracellular pH, sodium and tension in sheep cardiac Purkinje fibres. J Physiol (Lond) 1987; 390: 93–118.
Turvey SE, Allen DG. The use of SBFI to measure intracellular sodium in Langendorff perfused rat hearts. Proc Australian Physiol Pharmacol Soc 1992; 23: 143P.
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Allen, D.G., Cairns, S.P., Turvey, S.E., Lee, J.A. (1993). Intracellular Calcium and Myocardial Function During Ischemia. In: Sideman, S., Beyar, R. (eds) Interactive Phenomena in the Cardiac System. Advances in Experimental Medicine and Biology, vol 346. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2946-0_3
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DOI: https://doi.org/10.1007/978-1-4615-2946-0_3
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