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Myocardial fatty acid oxidation during ischemia and reperfusion

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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

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References

  1. 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

    Google Scholar 

  2. Liedtke JA: Alterations of carbohydrate and lipid metabolism in the acutely ischemic heart. Progress Cardiovasc Res 23: 321–336, 1981

    Google Scholar 

  3. Corr PB, Gross RW, Sobel BE: Amphopathic metabolites and membrane dysfunction in ischemic myocardium. Circ Res 55: 135–154, 1984

    Google Scholar 

  4. Van der Vusse GJ, Stam H: Lipid and carbohydrate metabolism in the ischaemic heart. Basic Res Cardiol 82 (suppl 1): 149–154, 1987

    Google Scholar 

  5. 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

    Google Scholar 

  6. 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

    Google Scholar 

  7. 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

    Google Scholar 

  8. Siegmund B, Klietz T, Schwartz P, Piper HM: Temporary contractile blockade prevents hypercontracture in anoxic-reoxygenated cardiomyocytes. Am J Physiol 260: H426-H435, 1991

    Google Scholar 

  9. 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

    Google Scholar 

  10. 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

    Google Scholar 

  11. 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

    Google Scholar 

  12. Kanaide H, Taira Y, Nakamura M: Transmural anoxic wave front and regional dysfunction during early ischemia. Am J Physiol 253: H240-H247, 1987

    Google Scholar 

  13. 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

    Google Scholar 

  14. 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

    Google Scholar 

  15. 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

    Google Scholar 

  16. Allen DG, Orchard CH: Myocardial contractile function during ischemia and hypoxia. Circ Res 60: 153–168, 1987

    Google Scholar 

  17. 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

    Google Scholar 

  18. Nishioka K, Jarmakani JM: Effect of ischemia on mechanical function and high-energy phosphates in rabbit myocardium. Am J Physiol 242: H1077-H1083, 1982

    Google Scholar 

  19. 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

    Google Scholar 

  20. 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

    Google Scholar 

  21. Ichihara K, Neely JR: Recovery of ventricular function in reperfused ischemic rat hearts exposed to fatty acids. Am J Physiol 249: 492–497, 1985

    Google Scholar 

  22. Neely JR, Feuvray D: Metabolic products and myocardial ischemia. Am J Pathol 102: 282–291, 1981

    Google Scholar 

  23. 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

    Google Scholar 

  24. Katz AM, Messineo FC: Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium. Circ Res 48: 1–16, 1981

    Google Scholar 

  25. 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

    Google Scholar 

  26. 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

    Google Scholar 

  27. 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

    Google Scholar 

  28. 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

    Google Scholar 

  29. 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

    Google Scholar 

  30. 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

    Google Scholar 

  31. 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

    Google Scholar 

  32. 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

    Google Scholar 

  33. 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

    Google Scholar 

  34. Schott RJ, Rohmann S, Braun ER, Schaper W: Ischemic preconditioning reduces infarct size in swine myocardium. Circ Res 66: 1133–1142, 1990

    Google Scholar 

  35. 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

    Google Scholar 

  36. Lerch R, Papageorgiou I, Benzi R: Role of mitochondrial calcium transport in myocardial hypermetabolism after reperfusion (abstract). Circulation 82 (suppl III): III-756, 1990

    Google Scholar 

  37. Neely JR, Rovetto MJ, Oram JF: Myocardial utilization of carbohydrate and lipids. Progress Cardiovasc Dis 15: 289–329, 1972

    Google Scholar 

  38. 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

    Google Scholar 

  39. 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

    Google Scholar 

  40. Renstrom B, Nellis SH, Liedtke AJ: Metabolic oxidation of glucose during early myocardial reperfusion. Circ Res 65: 1094–1101, 1989

    Google Scholar 

  41. 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

    Google Scholar 

  42. Huang XQ, Liedtke AJ: Alterations in fatty acid oxidation in ischemic and reperfused myocardium. Molec Cell Biochem 88: 145–153, 1989

    Google Scholar 

  43. 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

    Google Scholar 

  44. 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

    Google Scholar 

  45. 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

    Google Scholar 

  46. Carafoli E: The homeostasis of calcium in heart cells. J Mol Cell Cardiol 17: 203–212, 1985

    Google Scholar 

  47. 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

    Google Scholar 

  48. Poole-Wilson PA, Harding DP, Boudillon PDV, Tones MA: Calcium out of control. J Mol Cell Cardiol 16: 175–187, 1984

    Google Scholar 

  49. 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

    Google Scholar 

  50. 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

    Google Scholar 

  51. Chamberlain BK, Volpe P, Fleischer S: Inhibition of calciuminduced calcium release from purified cardiac sarcoplasmic reticulum vesicles. J Biol Chem 259: 7547–7553, 1984

    Google Scholar 

  52. 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

    Google Scholar 

  53. 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

    Google Scholar 

  54. 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

    Google Scholar 

  55. Liedtke AJ, Renstrom B, Nellis SH, Whitesell LF: Compromised metabolism in chronically reperfused pig hearts (abstract). J Am Coll Cardiol 17: 37A, 1991

    Google Scholar 

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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

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