Summary
The focus of this review centered on describing the effects of excess fatty acids on myocardial recovery during reperfusion following ischemic stress. Effects on mechanical function were modest in our studies and are likely to remain difficult/impossible to measure due to the independent phenomenon of stunning which obfuscates and no doubt dominates the influences of other mechanical determinants. Mitochondria appear capable of again using long-chain fatty acids as a preferred substrate and in the presence of restored oxygen delivery can produce normal levels of CO2. These changes in oxidative metabolism are not mirrored by equal recoveries in mitochondrial energetics. Because of inefficiencies in electron transport and oxidative phosphorylation together with moderate uncoupling of electron transport from oxidative phosphorylation, ATP resynthesis is blunted. This explains in part the absolute decrease in contents of exchangeable nucleotides noted both in cytosol and mitochondria. Further impairments in recovery reside in the inability of the mitochondria to exchange adenine nucleotides into cytosol through the adenine nucleotide translocase antiport. These findings contribute to our understanding of mechanical stunning and may be of value in designing future strategies to optimize the handling of substrates during myocardial reperfusion.
Visiting scientist from the Shang Hai Second Medical University, Peoples Republic of China
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Corr PB, Gross RW, Sobel BE: Arrhythmogenic amphiphilic lipids and the myocardial cell membrane. J Mol Cell Cardiol 14: 619–626, 1982
Hoak JC, Connor WE, Eckstein JW, Warner ED: Fatty acid-induced thrombosis and death: Mechanism and prevention. J Lab Clin Med 63: 791–800, 1964
Katz AM, Messineo FC: Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium. Circ Res 48: 1–16, 1981
Liedtke AJ: Alterations of carbohydrate and lipid metabolism in the acutely ischemic heart. Prog Cardiovasc Dis 23: 321–336, 1981
Neely JR, Morgan HE: Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. Ann Rev Physiol 36: 413–459, 1976
Oliver MF, Kurien VA, Greenwood TW: Relation between serum-free-fatty-acids and arrhythmias in death after acute myocardial infarction. Lancet 1: 710–714, 1968
Opie LH: Effects of regional ischemia on metabolism of glucose and fatty acids. II. Metabolic regulation in ischemia and hypoxia. Circ Res 38 (Suppl I): 52–68, 1976
Liedtke AJ: Lipid burden in ischemic myocardium. J Mol Cell Cardiol 20 (Suppl II): 65–74, 1988
Schwaiger M, Hansen H, Selin C, Vinten-Johanson J, Henze E, Schelbert HR: Prolonged metabolic alterations during reperfusion after transient ischemia in canine myocardium. Circulation 66 (11–158), 1982
Schwaiger M, Schelbert HR, Keen R, Vinten-Johansen J, Hansen H, Selin C, Barrio J, Huang SC, Phelps ME: Retention and clearance of C-11 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
Ichiharo K, Neely JR: Recovery of ventricular function in reperfused ischemic rat hearts exposed to fatty acids. Am J Physiol 249 (Heart Circ Physiol 18): H492–H497, 1985
Paulson DJ, Schmidt MJ, Romens J, Shug AL: Metabolic and physiological differences between zero-flow and low-flow myocardial ischemia: effects of L-acetyl carnitine. Bas Res Cardiol 79: 551–561, 1984
Mak IT, Kramer JH, Weglicki WB: Potentiation of free radical-induced lipid peroxidative injury to sarcolemmal membranes by lipid amphiphiles. J Biol Chem 261: 1153–1157, 1986
Kotaka K, Miyazaki Y, Ogawa K, Satake T, Sugiyama S, Ozawa T: Reversal of ischemia-induced mitochondrias dysfunctions after coronary reperfusions. J Mol Cell Cardiol 14: 223–231, 1982
Liedtke AJ, Mahar CO, Ytrehus K, Mjos OD: Estimates of free-radical production in rat and swine hearts: method and application of measuring malondialdehyde levels in fresh and frozen myocardium. Bas Res Cardiol 79: 513–518, 1984
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
Braunwald E, Kloner RA: Myocardial reperfusion: A double-edged sword? J Clin Invest 76: 1713–1719, 1985
Braunwald E, Kloner RA: The stunned myocardium: prolonged, post-ischemic ventricular dysfunction. Circulation 66: 1146–1149, 1982
Kloner RA, DeBoer LWV, Darsee JR, Engwall JS, Hale S, Tumas J, Braunwald E: Prolonged abnormalities of myocardium salvaged by reperfusion. Am J Physiol 241 (Heart Circ Physiol 10): H591–H599, 1981
Reibel DK, Rovetto MJ: Myocardial ATP synthesis and mechanical function following oxygen deficiency. Am J Physiol 234 (Heart Circ Physiol 3): H620–H624, 1978
Glower DD, Spratt JA, Newton JR, Wolfe JA, Rankin JS, Swain JL: Dissociation between early recovery of regional function and purine nucleotide content in postischemic myocardium in the conscious dog. Cardiovasc Res 21: 328–336, 1987
Neely JR, Grotyohann LW: Role of glycolytic products and damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts. Circ Res 55: 816–824, 1984
Sunnergren KP, Rovetto MJ: Myocyte and endothelial injury with ischemic reperfusion in isolated rat hearts. Am J Physiol 252 (Heart Circ Physiol 21): H1211–H1217, 1987
Schaper W, Binz K, Sass S, Winkler B: Influences of collateral blood flow and variations in MVO2 on tissue-ATP content in ischemic and infarcted myocardium. J Mol Cell Cardiol 19: 19–37, 1987
Demaison L, Liedtke AJ, Shrago E, Nellis SH: Effects of reperfusion on mitochondrial function in heart muscle. J Am Coll Cardiol 11: 38A, 1988
Greenfield RA, Swain JL: Disruption of myofibrillar energy use: Dual mechanisms that may contribute to postischemic dysfunction in stunned myocardium. Circ Res 60: 283–289, 1987
Bush LR, Buja LM, Tilton G, Wathen M, Apprill P, Ashton J, Willerson JT: Effects of propranolol and diltiazem alone and in combination on the recovery of left ventricular segmental function after temporary coronary occlusion and long-term reperfusion in conscious dogs. Circulation 72: 413–430, 1985
Knabb RM, Rosamond TL, Fox KAA, Sobel BE, Bergmann SR: Enhancement of salvage of reperfused ischemic myocardium by diltiazem. J Am Coll Cardiol 8: 861–871, 1986
Pagani M, Vatner SF, Baig H, Braunwald E: Initial myocardial adjustments to brief periods of ischemia and reperfusion in the conscious dog. Circ Res 43: 83–92, 1978
Stahl LD, Aversano TR, Becker LC: Selective enhancement of function of stunned myocardium by increased flow. Circulation 74: 843–851, 1986
DeBoer LWV, Bailin SJ, Dahmen DF, Byler RM, Clausius CR, Liedtke AJ: Inosine improves recovery of ‘stunned’ myocardium after transient ischemia. J Am Coll Cardiol 9: 126A, 1987
Zimmer HG, Trendelenburg C, Kammermeier H, Gerlach E: De novo synthesis of myocardial adenine nucleotides in the rat. Acceleration during recovery from oxygen deficiency. Circ Res 32: 635–642, 1973
Ambrosio G, Becker LC, Hutchins GM, Weisman HF, Weisfeldt ML: Reduction in experimental infarct size by recombinant human superoxide dismutase: Insights into the pathophysiology of reperfusion injury. Circulation 74: 1424–1433, 1986
Ambrosio G, Weisfeldt ML, Jacobus WE, Flaherty JT: Evidence for a reversible oxygen radical-mediated component of reperfusion injury: Reduction by recombinant human superoxide dismutase administered at the time of reflow. Circulation 75: 282–291, 1987
Myers ML, Bolli R, Lekich RF, Hartley CJ, Roberts R: Enhancement of recovery of myocardial function by oxygen free-radical scavengers after reversible regional ischemia. Circulation 72: 915–921, 1985
Nasslund U, Haggmark S, Johansson G, Marklund SL, Reiz S, Oberg A: Superoxide dismutase and catalase reduce infarct size in a porcine myocardial occlusion-reperfusion model. J Mol Cell Cardiol 18: 1077–1084, 1986
Becker LC, Levine JH, DiPaula AF, Guarnieri T, Aversano M: Reversal of dysfunction in post ischemic stunned myocardium by epinephrine and post extrasystolic potentiation. J Am Coll Cardiol 7: 580–589, 1986
Lavallee M, Cox D, Patrick TA, Vatner SF: Salvage of myocardial function by coronary artery reperfusion 1, 2, and 3 hours after occlusion in conscious dogs. Circ Res 53: 235–247, 1983
Mercier JC, Lando U, Kanmatsuse K, Ninomiya K, Meerbaum S, Fishbein MC, Swan HJC, Ganz W: Divergent effects of inotropic stimulation on the ischemic and severely depressed reperfused myocardium. Circulation 66: 395–400, 1982
Paulson DJ, Traxler J, Schmidt M, Noonan J, Shug AL: Protection of the ischaemic myocardium by L-propionylcarnitine: Effects on the recovery of cardiac output after ischaemia and reperfusion, carnitine transport and fatty acid oxidation. Cardiovasc Res 20: 536–541, 1986
Liedtke AJ, Demaison L, Nellis SH: Effects of L-propionylcarnitine on mechanical recovery during reflow in intact hearts. Am J Physiol 255 (Heart Circ Physiol 24): H169–H176, 1988
Liedtke AJ: Secondary carnitine deficiency in cardiac disease. In PR Borum (eds) Clinical Aspects of Human Carnitine Deficiency. Pergamon Press, New York, 1986, pp 204–215
Weiss ES, Hoffman EJ, Phelps ME, Welch MJ, Henry PD, Ter-Pogossian MM, Sobel BE: External detection and visualization of myocardial ischemia with 14C-substrates in vitro and in vivo. Circ Res 39: 24–32, 1976
Lerch RA, Bergmann SR, Ambros HD, Welch MJ, Ter-Pogossian MM, Sobel BE: Effect of flow-independent reduction of metabolism on regional myocardial clearance of 14C-palmitate. Circulation 65: 731–738, 1982
Shelbert HR, Phelps ME, Hoffman E, Huang SC, Kuhl DE: Regional myocardial blood flow, metabolism and function assessed noninvasively with positron emission tomography. Am J Cardiol 46: 1269–1277, 1980
Liedtke AJ, Hughes HC, Neely JR: Metabolic response to varying restrictions of coronary blood flow in swine. Am J Physiol 228: 655–662, 1975
Liedtke AJ, Hughes HC: Effects of hyperthermic stress on myocardial function during experimental coronary ischemia. Circ Res 39: 647–653, 1976
Liedtke AJ, Nellis SH, Mjos OD: Effects of reducing fatty acid metabolism on mechanical function in regionally ischemic hearts. Am J Physiol (Heart Circ) 16: H387–H394, 1984
Miller WP, Liedtke AJ, Nellis SH: Effects of 2-tetradecylglycidic acid on myocardial function in swine hearts. Am J Physiol (Heart Circ Physiol) 20: H547–H553, 1986
Molaparast-Saless F, Liedtke AJ, Nellis SH: Effects of the fatty acid blocking agents, oxfenicine and 4-bromocrotonic acid, on performance in aerobic and ischemic myocardium. J Mol Cell Cardiol 19: 509–520, 1987
Liedtke AJ, Nellis SH: Effects of carnitine isomers on fatty acid metabolism in ischemic hearts. Circ Res 48: 859–866, 1981
Fox KAA, Abendschein DR, Ambos HD, Sobel BE, Bergmann SR: Efflux of metabolized and nonmetabolized fatty acid from canine myocardium. Implications for quantifying myocardial metabolism tomographically. Circ Res 57: 232–243, 1985
Rosamond TL, Abendschein DR, Sobel BE, Bergmann SR, Fox KAA: Metabolie fate of radiolabeled palmitate in ischemic canine myocardium: Implications for positron emission tomography. J Nucl Med 28: 1322–1329, 1987
Myears DW, Sobel BE, Bergmann SR: Substrate use in ischemic and reperfused canine myocardium: quantitative considerations. Am J Physiol 253 (Heart Circ Physiol 22): H107–H114, 1987
Kane JJ, Murphy ML, Bissett JK, deSoyza N, Doherty JE, Straub KD: Mitochondrial function, oxygen extraction, epicardial S-T segment changes and tritiated digoxin distribution after reperfusion of ischemic myocardium. Am J Cardiol 36: 218–224, 1975
Bush LR, Shlafer M, Haack DW, Lucchesi BR: Time-dependent changes in canine cardiac mitochondrial function and ultrastructure resulting from coronary occlusion and reperfusion. Bas Res Cardiol 75: 555–571, 1980
Asimakis GK, Conti VR: Myocardial ischemia: Correlation of mitochondrial adenine nucleotide and respiratory function. J Mol Cell Cardiol 16: 439–448, 1984
Peng CF, Murphy ML, Straub KD: Effects of early reperfusion on the mechanical and biochemical characteristics of ischemic myocardium. J Surg Res 41: 493–502, 1986
Peng CF, Davis JL, Murphy ML, Straub KD: Effects of reperfusion on myocardial wall thickness, oxidative phosphorylation and Ca2+ metabolism following total and partial myocardial ischemia. Am J Heart J 112: 1238–1244, 1986
Zimmer HG: Adenine nucleotide biosynthesis in cardiac muscle: Regulation and intervention. Adv Exp Med Biol 165: 469–475, 1984
Zimmer HG, Ibel H: Ribose accelerates the repletion of the ATP pool during recovery from reversible ischemia of the rat heart. J Mol Cell Cardiol 16: 863–866, 1984
Ibel H, Zimmer HG: Metabolic recovery following temporary regional myocardial ischemia in the rat. J Mol Cell Cardiol 18 (Suppl 4): 61–65, 1986
Murphy ML, Peng CF, Kane JJ, Straub KD: Ventricular performance and biochemical alteration of regional ischemic myocardium after reperfusion in the pig. Am J Cardiol 50: 821–828, 1982
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275, 1951
Hagihara B: Techniques for the application of polarography to mitochondrial respiration. Biochem Biophys Acta 46: 134–142, 1961
Estabrook RW: Mitochondrial respiratory control and the polygraphic measurement of ADP:O ratios. Meth Enzymology 10: 41–47, 1967
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 Kluwer Academic Publishers
About this chapter
Cite this chapter
Huang, X.Q., Liedtke, A.J. (1989). Alterations in fatty acid oxidation in ischemic and reperfused myocardium. In: Van Der Vusse, G.J. (eds) Lipid Metabolism in Normoxic and Ischemic Heart. Developments in Molecular and Cellular Biochemistry, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1611-4_21
Download citation
DOI: https://doi.org/10.1007/978-1-4613-1611-4_21
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4612-8891-6
Online ISBN: 978-1-4613-1611-4
eBook Packages: Springer Book Archive