Abstract
Inhibition of fatty acid oxidation is an early event in myocardial ischemia that most likely contributes to tissue injury by the accumulation of potentially toxic intermediates such as acylCoA and acylcarnitine. After reperfusion both myocardial oxygen consumption and fatty acid oxidation may rapidly recover to preischemic levels, even when contractile function remains depressed. The mechanisms underlying the apparent dissociation between contractile function and oxidative metabolism early during reperfusion are still controversial. In isolated rat hearts subjected to 60 min of no-flow ischemia myocardial oxygen consumption and oxidation of palmitate were lowered during reperfusion by 3 mM of NiCl2 and by 6 µM of ruthenium red. The results provide indirect evidence for the hypothesis that intracellular calcium transport may be involved in the mechanisms responsible for the high oxidative metabolic rate early after reperfusion
Similar content being viewed by others
References
Opie LH: Effects of regional ischemia on metabolism of glucose and fatty acids. Relative rates of aerobic and anaerobic energy production during myocardial infarction and comparison with effects of anoxia. Circ Res 38 (suppl I): 152–186, 1976
Liedtke JA: Alterations of carbohydrate and lipid metabolism in the acutely ischemic heart. Progress Cardiovasc Res 23: 321–336, 1981
Corr PB, Gross RW, Sobel BE: Amphopathic metabolites and membrane dysfunction in ischemic myocardium. Circ Res 55: 135–154, 1984
Van der Vusse GJ, Stam H: Lipid and carbohydrate metabolism in the ischaemic heart. Basic Res Cardiol 82 (suppl 1): 149–154, 1987
Liedtke JA, Shrago E: Detrimental effects of fatty acids and their derivatives in ischemic and reperfused myocardium. In: HM Piper (ed) Pathophysiology of severe myocardial injury. Kluwer Academic Publishers, Dordrecht, 1990, pp 149–166
Bourdillon PD, Poole-Wilson PA: The effects of verapamil, quiescence, and cardioplegia on calcium exchange and mechanical function in ischemic rabbit myocardium. Circ Res 50: 360–368, 1982
Garlick PB, Davies MJ, Hearse DJ, Slater TF: Direct determination of free radicals in the reperfused rat heart using electron spin resonance spectroscopy. Circ Res 61: 757–760, 1987
Siegmund B, Klietz T, Schwartz P, Piper HM: Temporary contractile blockade prevents hypercontracture in anoxic-reoxygenated cardiomyocytes. Am J Physiol 260: H426-H435, 1991
Hearse DJ, Humphrey SM, Chain EB: Abrupt reoxygenation of the anoxic potassium-arrested perfused rat heart: A study of myocardial enzyme release. J Mol Cell Cardiol 5: 395–407, 1973
Heyndrickx GR, Millard RW, McRitchie RJ, Maroko PR, Vatner SF: Regional myocardial function and electrophysiological alterations after brief coronary artery occlusion in conscious dogs. J Clin Invest 56: 978–985, 1975
Bergmann SR, Lerch RA, Fox KAA, Ludbrook PA, Welch MJ, Ter-Pogossian MM, Sobel BE: Temporal dependence of beneficial effects of coronary thrombolysis characterized by positron tomography. Am J Med 73: 573–581, 1982
Kanaide H, Taira Y, Nakamura M: Transmural anoxic wave front and regional dysfunction during early ischemia. Am J Physiol 253: H240-H247, 1987
Whitmer JT, Idell-Wenger JA, Rovetto MJ, Neely JR: Control of fatty acid metabolism in ischemic and hypoxic hearts. J Biol Chem 253: 4305–4309, 1978
Healy-Moore K, Radloff JF, Hull FE, Sweeley CC: Incomplete fatty acid oxidation by ischemic heart: β-hydroxy fatty acid production. Am J Physiol 239: H257-H265, 1980
Van Bilsen M, Van der Vusse GJ, Willemsen PHM, Coumans WA, Roemen THM, Reneman RS: Lipid alterations in isolated, working rat hearts during ischemia and reperfusion: Its relation to myocardial damage. Circ Res 64: 304–314, 1989
Allen DG, Orchard CH: Myocardial contractile function during ischemia and hypoxia. Circ Res 60: 153–168, 1987
Reimer KA, Jennings RB, Hill ML: Total ischemia in dog hearts, in vitro. 2. High energy phosphate depletion and associated defects in energy metabolism, cell volume regulation, and sarcolemmal integrity. Circ Res 49: 901–911, 1981
Nishioka K, Jarmakani JM: Effect of ischemia on mechanical function and high-energy phosphates in rabbit myocardium. Am J Physiol 242: H1077-H1083, 1982
Chien KR, Han A, Sen A, Buja M, Willerson JT: Accumulation of unesterified arachidonic acid in ischemic canine myocardium. Relationship to a phosphatidylcholine deacylation-reacylation cycle and the depletion of membrane phospholipids. Circ Res 54: 313–322, 1984
Paulson DJ, Schmidt MJ, Romens J, Shug AL: Metabolic and physiological differences between zero-flow and low-flow myocardial ischemia: effects of L-acetylcarnitine. Basic Res Cardiol 79: 551–561, 1984
Ichihara K, Neely JR: Recovery of ventricular function in reperfused ischemic rat hearts exposed to fatty acids. Am J Physiol 249: 492–497, 1985
Neely JR, Feuvray D: Metabolic products and myocardial ischemia. Am J Pathol 102: 282–291, 1981
Moore KH, Bonema JD, Solomon FJ: Long chain acyl-CoA and acylcarnitine hydrolase activities in normal and ischemic rabbit hearts. J Mol Cell Cardiol 16: 905–913, 1984
Katz AM, Messineo FC: Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium. Circ Res 48: 1–16, 1981
Schoonderwoerd K, van der Kraij T, Hülsmann WC, Stam H: Hormones and triacylglycerol metabolism under normoxic and ischemic conditions. Mol Cell Biochem 88: 129–137, 1989
Bilheimer D, Buja LM, Parkey RW, Bonte FJ, Willerson JT: Fatty acid accumulation and abnormal lipid deposition in peripheral border zones of experimental myocardial infarcts. J Nucl Med 19: 276–283, 1978
Crass MF, Sterrett PR: Distribution of glycogen and lipids in the ischemic canine left ventricle: Biochemical and light and electron microscopic correlates. In: PE Roy and G Rona (eds) Recent advances in studies on cardiac structure and metabolism. University Park Press, Baltimore, 1975, pp 251–263
Van der Vusse GJ, Roemen THM, Prinzen FW, Coumans WA, Reneman RS: Uptake and tissue content of fatty acids in dog myocardium under normoxic and ischemic conditions. Circ Res 50: 538–546, 1982
Trach V, Buschmans-Denkel E, Schaper W: Relation between lipolysis and glycolysis during ischemia in the isolated rat heart. Basic Res Cardiol 81: 454–464, 1986
Schoonderwoerd K, Broekhoven-Schokker S, Hiilsmann WC, Stam H: Enhanced lipolysis of myocardial triglycerides during low-flow ischemia and anoxia in the isolated rat heart. Basic Res Cardiol 84: 165–173, 1989
Gorge G, Chatelain P, Schaper J, Lerch R: Effect of increasing degrees of ischemic injury on myocardial oxidative metabolism early after reperfusion in isolated rat hearts. Circ Res 68: 1681–1692, 1991
Stahl LD, Weiss HR, Becker LC: Myocardial oxygen consumption, oxygen supply/demand heterogeneity, and microvascular patency in regionally stunned myocardium. Circulation 77: 865–872, 1988
Laxson DD, Homans DC, Dai X-Z, Sublett E, Bache RJ: Oxygen consumption and coronary reactivity in postischemic myocardium. Circ Res 64: 9–20, 1989
Schott RJ, Rohmann S, Braun ER, Schaper W: Ischemic preconditioning reduces infarct size in swine myocardium. Circ Res 66: 1133–1142, 1990
Brown MA, Nohara R, Vered Z, Perez JE, Bergmann SR: The dependence of recovery of stunned myocardium on restoration of oxidative metabolism (abstract). Circulation 78 (suppl II): II-467, 1988
Lerch R, Papageorgiou I, Benzi R: Role of mitochondrial calcium transport in myocardial hypermetabolism after reperfusion (abstract). Circulation 82 (suppl III): III-756, 1990
Neely JR, Rovetto MJ, Oram JF: Myocardial utilization of carbohydrate and lipids. Progress Cardiovasc Dis 15: 289–329, 1972
Lopaschuk GD, Spafford MA, Davies NJ, Wall SR: Glucose and palmitate oxidation in isolated working rat hearts reperfused after a period of transient global ischemia. Circ Res 66: 546–553, 1990
Liedtke AJ, Demaison L, Eggleston AM, Cohen LM, Nellis SH: Changes in substrate metabolism and effects of excess fatty acids in reperfused myocardium. Circ Res 62: 535–542, 1988
Renstrom B, Nellis SH, Liedtke AJ: Metabolic oxidation of glucose during early myocardial reperfusion. Circ Res 65: 1094–1101, 1989
Sarnoff SJ, Braunwald E, Welch GH Jr, Case RB, Stainsby WN, Macruz R: Hemodynamic determinants of oxygen consumption of heart with special reference to tension-time index. Am J Physiol 192: 148–156, 1958
Huang XQ, Liedtke AJ: Alterations in fatty acid oxidation in ischemic and reperfused myocardium. Molec Cell Biochem 88: 145–153, 1989
Marban E, Kitakaze M, Koretsune Y, Yue DT, Chacko VP, Pike MM: Quantification of (Ca2+)i in perfused hearts. Critical evaluation of the 5F-BABTA and nuclear magnetic resonance method as applied to the study of ischemia and reperfusion. Circ Res 66: 1255–1267, 1990
Nayler WG, Ferrari R, Williams A: Protective effect of pretreatment with verapamil, nifedipine and propranolol on mitochondrial function in the ischemic reperfused myocardium. Amer J Cardiol 46: 242–248, 1980
Kusuoka H, Koretsune Y, Chacko VP, Weisfeldt ML, Marban E: Excitation-contraction coupling in postischemic myocardium. Does failure of activator Ca2+ transients underlie stunning? Circ Res 66: 1268–1276, 1990
Carafoli E: The homeostasis of calcium in heart cells. J Mol Cell Cardiol 17: 203–212, 1985
Vercesi A, Reynafarje B, Lehninger A: Stoichiometry of H+ ejection and Ca2+ uptake coupled to electron transport in rat heart mitochondria. J Biol Chem 253: 6379–6385, 1978
Poole-Wilson PA, Harding DP, Boudillon PDV, Tones MA: Calcium out of control. J Mol Cell Cardiol 16: 175–187, 1984
Peng CF, Kane JJ, Straub KD, Murphy ML: Improvement of mitochondrial energy production in ischemic myocardium byin vivo infusion of ruthenium red. J Cardiovasc Pharmacol 2: 45–54, 1980
Henry PD, Shuchleib R, Davis J, Weiss ES, Sobel BE: Myocardial contracture and accumulation of mitochondrial calcium in ischemic rabbit heart. Am J Physiol 233: H677-H684, 1977
Chamberlain BK, Volpe P, Fleischer S: Inhibition of calciuminduced calcium release from purified cardiac sarcoplasmic reticulum vesicles. J Biol Chem 259: 7547–7553, 1984
Schwaiger M, Schelbert HR, Keen R, Vinten-Johansen J, Hansen H, Selin C, Barrio J, Huang SC, Phelps ME: Retention and clearance of11C-palmitic acid in ischemic and reperfused canine myocardium. J Am Coll Cardiol 6: 311–320, 1985
Schwaiger M, Schelbert HR, Ellison D, Hansen H, Yeatman L, Vinten-Johansen J, Selin C, Barrio J, Phelps ME: Sustained regional abnormalities in cardiac metabolism after transient ischemia in the chronic dog model. J Am Coll Cardiol 6: 336–347, 1985
Lerch RA, Bergmann SR, Ambos HD, Welch MJ, Ter-Pogossian MM, Sobel BE: Effect of flow-independent reduction of metabolism on regional myocardial clearance of11C-palmitate. Circulation 65: 731–738, 1982
Liedtke AJ, Renstrom B, Nellis SH, Whitesell LF: Compromised metabolism in chronically reperfused pig hearts (abstract). J Am Coll Cardiol 17: 37A, 1991
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lerch, R., Tamm, C., Papageorgiou, I. et al. Myocardial fatty acid oxidation during ischemia and reperfusion. Mol Cell Biochem 116, 103–109 (1992). https://doi.org/10.1007/BF01270576
Issue Date:
DOI: https://doi.org/10.1007/BF01270576