Abstract
It is hypothesized that intracellular Ca2+ overload is a cause of prolonged post-ischemic ventricular dysfunction. We studied the effects of amiloride and of increasing extracellular Ca2+ concentration on the functional recovery of isolated reperfused imature rabbits.
Isolated working hearts from one-week-old rabbits were subjected to a 40-minute period of global ischemia followed by 30 minutes of aerobic reperfusion. Contractile function was 45% of the preischemic level in hearts reperfused with buffer containing 1.75 mM Ca2+ (group 1). No significant difference in recovery of mechanical function was seen between hearts in which 300 μM amiloride was added five minutes before the onset of ischemia (group 2) and in hearts of group 1. When Ca2+ was increased to 2.5 mM during reperfusion (group 3), mechanical function was significantly recovered to 128% of the preischemic level, There were no significant differences in efflux of both lactate and creatine phosphokinase among the three groups.
Therefore, we conclude that, unlike the adult heart, increasing Ca2+ during reperfusion may be beneficial for reperfused one-week-old rabbit hearts rather than adding amiloride five minutes before ischemia.
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References
Sawa Y, Matsuda M, Shimazaki Y, Hirose M, Kadoba K, Takami H, Nakada T, Kawashima Y. 1987. Ultrastructual assessmant of the infant myocardium receiving crystalloid cardioplegia. Circulation 76(Suppl V):V141–V155.
del Nido PJ, Mickle DAG, Wilson GJ, Benson LN, Weisel RD, Coles JG, Trusler GA, William WG. 1988, Inadequate myocardial protection with cold cardioplegic arrest during repair of tetralogy of Fallot. J Thorac Cardiovasc Surg 95:223–229.
Avrikan M, Hearse DJ. 1989. Protection of the myocardium during global ischemia: is crystalloid cardioplegia effective in the immature myocardium? J Thorac Cardiovasc Surg 97:220–228.
Itoi T, Huang L, Lopaschuk GD. 1993. Glucose use in neonatal rabbit hearts reperfused after global ischemia. Am J Physiol 265 (Heart Circ Physiol 34):H427–H433.
Jarmakani JM, Nakanish T, George BL, Bers D. 1982. Effect of extracellular calcium on myocardial mechanical function in the neonatal rabbit. Dev Pharmacol Ther 5:1–13.
Riva E, Hearse DJ. 1991. Isolated, perfused neonatal rat heart preparation for studies of calcium and functional stability. Ann Thorac Surg 52:987–992.
Kuroda H, Ishiguro S, Mori T. 1986. Optimal calcium concentration in the initial perfusate for post-ischemic myocardial performance (calcium concentration during reperfusion). J Mol Cell Cardiol 18:625–633.
du Toit E, Opie LH. 1992. Modulation of severity of reperfusion stunning in the isolated rat heart by agents altering calcium flux at onset of reperfusion. Circ Res 70:965–967.
Jeremy RW, Koretsune Y, Marban E, Becker LC. 1992. Relation between glycolysis and calcium homeostasis in post-ischemic myocardium. Circ Res 70:1180–1190.
Itoi T, Lopaschuk GD. 1996. Calcium improves mechanical function and carbohydrate metabolism following ischemia in isolated bi-ventricular working hearts from immature rabbits. J Mol Cell Cardiol 28:1501–1514.
Tani M. 1990. Mechanisms of Ca2+ overload in reperfused ischemic myocardium. Annu Rev Physiol 52:543–559.
Crespo LM, Granthan CJ, Cannell MB. 1990. Kinetics, stoichiometry and role of the Na-Ca exchange mechanism in isolated cardiac myocytes. Nature 345:618–621.
Reuter H. 1991. Ins and outs of Ca2+ transport. Nature 349:567–568.
Steenbergen C, Murphy E, Watts JA, London RE. 1990. Correlation between cytosolic free calcium, contracture, ATP, and irreversible ischemic injury in perfused rat heart. Circ Res 66:135–146.
Mochizuki S, Seki S, Ejima M, Onodera T, Taniguchi M, Ishikawa S. 1993. Na+/H+ exchanger and reperfusion-induced ventricular arrhythmias in isolated perfused heart: possible role of amiloride. Mol Cell Biochem 119:151–157.
Murphy E, Perlman M, London RE, Steenbergan C. 1991. Amiloride delays the ischemia-induced rise in cytosolic free calcium. Circ Res 68:1250–1258.
Karmazyn M. 1988. Amiloride enhances postischemic ventricular recovery: possible role of Na+-H+ exchange. Am J Physiol 255 (Heart Circ Physiol 24):H608–H615.
Saddik M, Lopaschuk GD. 1991. Myocardial triglyceride turnover and contribution to energy substrate utilization in isolated working rat hearts. J Biol Chem 266:8162–8170.
Lopaschuk CD, Collins-Nakai R, Olley PM, Montague TJ, McNeil G, Gayle M, Penkoske P, Finegan BA. 1994. Plasma fatty acid levels in infants and adults following myocardial ischemia. Am Heart J 128:61–67.
McVeigh JJ, Lopaschuk GD. 1990. Dichloroacetate stimulation of glucose oxidation improves recovery of ischemic rat hearts. Am J Physiol 259 (Heart Circ Physiol 28):H1079–H1015.
Broderick TL, Quinney HA, Lopaschuk GD. 1993. Beneficial effect of carnitine on mechanical recovery of rat hearts reperfused after a transient period of global ischemia is accompanied by a stimulation of glucose oxidation. Circulation 87:972–981.
Kusuoka H, Marban E. 1992. Cellular mechanisms of myocardial stunning. Annu Rev Physiol 54:243–256.
Braunwald E, Kloner RA. 1982. The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulation 66:1146–1149.
Bolli R. 1990. Mechanism of myocardial “stunning”. Circulation 82:723–738.
Fliegel L, Dyck JRB. 1995. Molecular biology of the cardiac sodium/hydrogen exchanger. Cardiovasc Res 29:155–159.
Vandenberg JI, Metcalfe JC, Grace AA. 1993. Mechanism of pHi recovery after global ischemia in the perfused heart. Circ Res 72:993–1003.
Nakanishi T, Gu W, Seguchi M, Cragoe Jr EJ, Momma K. 1992. HCO3 −-dependent intracellular pH regulation in the premature myocardium. Circ Res 71:1314–1323.
Pridjian AK, Levitsky S, Krukenkamp I, Silverman NA, Feinberg H. 1987. Developmental change in reperfusion injury. A comparison of intracellular cation accumulation in the newborn, neonatal, and adult heart. J Thorac Cardiovasc Surg 93:428–433.
Maylie JG. 1984. Excitation-contraction coupling in neonatal and adult myocardium of cat. Am J Physiol 242 (Heart Circ Physiol 11):H834–H843.
Nakanishi T, Jarmakani JM. 1984. Developmental changes in myocardial mechanical function and subcellular organelles. Am J Physiol 246 (Heart Circ Physiol 15):H615–H625.
Mahony L, Jones LR. 1986. Developmental changes in cardiac sarcoplasmic reticulum in sheep. J Biol Chem 261:15257–15265.
Pegg W, Michalak M. 1987. Differentiation of sarcoplasmic reticulum during cardiac myogenesis. Am J Physiol 252 (Heart Circ Physiol 21):H22–H31.
Arai M, Otsu K, MacLennan DH, Periasamy M. 1992. Regulation of sarcoplasmic reticulum gene expression during cardiac and skeletal muscle development. Am J Physiol 262 (Cell Physiol 31):C614–C620.
Boucek RJ Jr, Shelton ME, Artman M, London E, Pettus R. 1985. Myocellular calcium regulation by the sarcolemmal membrane in the adult and immature rabbit heart. Basic Res Cardiol 80:316–325.
Artman M. 1992. Sarcolemmal Na+-Ca2+ exchange activity and exchanger immunoreactivity in developing rabbit hearts. Am J Physiol 263 (Heart Circ Physiol 32):H1506–1513.
Wetzel GT, Chen F, Klitzner TS. 1993. Ca2+ channel kinetics in acutely isolated fetal, neonatal, and adult rabbit cardiac myocytes. Circ Res 72:1065–1074.
Pearl JM, Laks H, Drinkwater DC, Meneshian A, Sun B, Gates RM, Chang P. 1993. Normocalcemic blood or crystalloid cardioplegia provide better neonatal myocardial protection than does low-calcium cardioplegia. J Thorac Cardiovasc Surg 105:201–206.
Aoki M, Nomura F, Kawata H, Mayer E. 1993. Effect of calcium and preischemic hypothermia on recovery of myocardial function after cardioplegic ischemia in neonatal lambs. J Thorac Cardiovasc Surg 105:207–213.
Caspi J, Herman SL, Coles JG, Benson LN, Radde I, Augustine J, Hamilton F, Caltellarin S, Kumar R, Wilson GJ. 1990. Effect of low perfusate Ca2+ concentration on newborn myocardial function after ischemia. Circulation 82(Suppl IV):IV371–IV379.
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Teramachi, S., Itoi, T., Onouchi, Z. (1998). Calcium but not Amiloride Improves the Mechanical Function of Reperfused One-Week-Old Rabbit Hearts. In: Mochizuki, S., Takeda, N., Nagano, M., Dhalla, N.S. (eds) The Ischemic Heart. Progress in Experimental Cardiology, vol 1. Springer, Boston, MA. https://doi.org/10.1007/978-0-585-39844-0_32
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DOI: https://doi.org/10.1007/978-0-585-39844-0_32
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