Summary
The influence of cardiac stunning on the oxidation of fatty acids and the oxidative phosphorylation in mitochondria was investigated. Rat hearts were perfused for 15 min according to the working mode with a Krebs-Henseleit buffer containing glucose (11 mM). The hearts were then maintained in normoxic conditions (C group) or subjected to a 15-min global no-flow normothermic ischemia followed by a 30-min reperfusion (R group). Throughout the perfusion, the aortic and coronary flows, and the heart rate and oxygen consumption were monitored. At the end of the perfusion procedure, a bolus of 1-14C palmitate was injected in the coronary arterial bed to evaluate the fatty acid oxidation. Two sub-populations of mitochondria were isolated from each heart by either mechanical (ME mitochondria) or enzymic (EE mitochondria) extraction and their respiration properties were evaluated. Furthermore, the mitochondrial energy production (ATP and creatine phosphate) was assessed. During ischemia, the aortic flow was suppressed and recovered only to approximately 50% of the preischemic value during reperfusion. This mechanical stunning was associated with an important reduction of the stroke volume (−37%,p<0.01) and a slight decrease in heart rate (−20%,p<0.001). At the end of reperfusion, the beta-oxidation rate constituted 55±1.7% of the cell palmitate and was similar to that assessed in the C group. The oxygen consumption was decreased to 216±31.0μL O2/min/gww and the venous O2 concentration increased to 5.1±0.572 μL O2/mL (instead of 2.9±0.342 μL O2/mL in the C group), although due to large SD, only the latter was statistically significant. A decrease in metabolic effeciency (42±14.4 vs 106±16.8 mL/μL O2 in the C group) and an increase in palmitate oxidation to oxygen consumption ratio (77±10.1 vs 47.6±4.25 % beta-oxidized palmitate/μL O2 in the C group) were observed. This increased fatty acid contribution in the oxidation metabolism could be responsible for some oxygen wasting and could contribute to decrease the energy available for the contraction despite the normal cardiac oxygen uptake. Furthermore, the respiration parameters of the mitochondria were similar in the C and R groups when glutamate (20 mM) or palmitoylcarnitine (25 μM) were used as substrate. ME mitochondria of R group displayed a reduced rate of ATP production (118±29.5 vs 180±14.5 nmoles/min/mg proteins in the C group) without altered creatine phosphate production. The presence of calcium in the medium (10−5 M) provoked a decrease in ATP production. These effects were not observed with EE mitochondria. Thus, a decreased energy production resulting from a substrate effect and/or a decreased mitochondrial phosphorylative capacity could be associated with the mechanical stunning.
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References
Allison TB, Holsinger J (1983) Myocardial metabolism and regional myocardial blood flow in the canine left ventricule following 20 minutes of circumflex artery occlusion and reperfusion. J Mol Cell Cardiol 15:151–161
Asimakis GK, Zwischenberger JB, Inners-McBride K, Sordhal LA, Conti VR (1992) Post-ischemic recovery of mitochondrial adenine nucleotides in the heart. Circulation 85:2212–2220
Bizerte C, Sezille G, Bertrand M, Jaillard J (1964) Chromatographie en couche mince des principales classes de lipides. Ann Biol Clin 22:861–897
Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917
Bolli R (1992) Myocardial “stunning in man. Circulation 86:1671–1691
Braunwald E, Kloner RA (1982) The stunned myocardium: prolonged, post-ischemic ventricular dysfunction. Circulation 66:1146–1149
Brooks WM, Willis RJ (1983) 31 P nuclear magnetic resonance study of the recovery characteristics of high energy phosphate compounds and intracellular pH after global ischemia in the perfused guinea-pig heart. J Mol Cell Cardiol 15:495–502
Chappell JB (1964) The oxidation of citrate, isocitrate and cis-aconitate by isolated mitochondria. Biochem J 90:225–237
Cuchet P, Demaison L, Bontemps L, Keriel C, Mathieu JP, Pernin C, Marti-Batlle D, Riche F, Vidal M, Comet M (1985) Do iodinated fatty acids undergo a nonspecific deiodination in the myocardium? Eur J Nucl Med 10:505–510
Dagnelie P (1975) Théories et méthodes statistiques. Presses agronomiques de Gembloux, Belgium, vol. 2
Deboer LWV, Ingwall JS, Kloner RA, Braunwald E (1980) Prolonged derangements of canine purine metabolism after a brief coronary artery occlusion not associated with anatomic evidence of necrosis. Proc Natl Acad Sci USA 77:5471–5475
Demaison L, Bontemps L, Keriel C, Dubois F, Mathieu JP, Pernin C, Marti-Battle D, Riche F, Vidal M, Comet M, Cuchet P, Bourdoiseau M, Coornaert S (1984) Myocardial metabolism studied with iodine-123 hexadecenoic acid. Radiopharmaceuticals and Labelled Compounds, 45:443–450
Demaison L, Liedtke AJ, Shrago E, Nellis SH, Woldegiorgis G (1989) Changes in energy metabolism and mitochondrial function in the reperfused working swine heart. J Applied Cardiol 4:431–440
Demaison L, Grynberg A (1991) Influence of dietary linseed oil and sunflower seed oil on some mechanical and metabolic parameters of isolated working rat hearts. Reprod Nutr Dev 31:37–45
Ehring T, Heusch G (1991) Postextrasystolic potentiation does not distinguish ischemic from stunned myocardium. Pflügers Arch 418:453–461
Ehring T, Böhm M, Heusch G (1992) The calcium antagonist nisoldipine improves the functional recovery of reperfused myocardium only when given before ischemia. J Cardiovasc Pharmac 20:63–74
Estabrook RW (1967) Mitochondrial respiratory control and polarographic measurement of ADP:O ratios. In: Estabrook RW And Pullman (ed) Methods in Enzymology; Academic Press, vol 10, New-York, pp 41–47
Ferrari R, Ceconi C, Curello S, Cargnoni A, Condorelli E, Belloli S, Albertini A, Visioli O (1988) Metabolic changes during post-ischemic reperfusion. J Mol Cell Cardiol 20: 119–133
Görge G, Papageorgiou I, Lerch R (1990) Epinephrine-stimulated contractile and metabolic reserve in post-ischemic rat myocardium. Basis Res Cardiol 85:595–605
Görge G, Chatelain P, Schaper J, Lerch R (1991) Effect of increasing degrees of ischemic injury on myocardial oxidative metabolism early after reperfusion in isolated rat hearts. Circ Res 68:1681–1692
Guarnieri T (1989) Direct measurement of [Ca2+]i in early and late reperfused myocardium. Circulation 80 (suppl Il):241
Guth BD, Martin JF, Heusch G, Ross J (1987) Regional myocardial blood flow, function and metabolism using phosphorus-31 nuclear magnetic resonance spectroscopy during ischemia and reperfusion in dogs. JACC 10:673–681
Harmsen E, De Tombe PPH, De Jong (1982) Simultaneous determination of myocardial adenine nucleotides and creatine phosphate by high-performance liquid chromatography. J Chromatography 230:131–136
Heyndrickx GR, Millard RW, McRitchie RJ, Maroko PR, Vatner SF (1975) Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs. J Clin Inv 56:978–985
Hoffmeister HM, Mauser M, Schaper W (1985) Effect of adenosine and AICAR on ATP content and regional contractile function in reperfused canine myocardium. Bas Res Cardiol 80:445–458
Ichihara K, Abiko Y (1984) Rebound recovery of myocardial creatine phosphate with reperfusion after ischemia. Am Heart J 108:1594–1597
Ito BR, Tate H, Kobayashi M, Schaper W (1987) Reversibly injured, postischemic canine myocardium retains normal contractile reserve. Circ Res 61:834–846
Jennings RB, Schaper J, Hill ML, Steenberger C, Reimer KA (1985) Effect of reperfusion late in the phase of reversible ischemic injury. Circ Res 56:262–278
Kitakaze M, Weisman HF, Marban E (1988) Contractile dysfunction and ATP depletion after transient calcium overload in perfused ferret hearts. Circulation 77:685–695
Kloner RA, Deboer LWV, Darsee JR, Ingwall JS, Hale S, Tumas J, Braunwald E (1981) Prolonged abnormalities of myocardium salvaged by reperfusion. Am J Physiol 241:H591–H599
Kloner RA, Ellis SG, Lange R, Braunwald E (1983) Studies of experimental coronary artery reperfusion. Effects of infarct size, myocardial function, biochemistry, ulstrastructure and microvascular damage. Circulation 68:I8–I15
Kusuoka H, Porterfield JK, Weisman HF, Weisfeldt ML, Marban E (1987) Pathophysiology and pathogenesis of stunned myocardium. Depressed Ca2+ activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts. J Clin Invest 79:950–961
Lee JA, Allen DG (1992) Changes in intracellular free calcium concentration during long exposures to simulated ischemia in isolated mammalian ventricular muscle. Circ Res 71:58–69
Liedtke AJ, Nellis S, Neely JR (1978) Effects of excess free fatty acids on mechanical and metabolic function in normal and ischemic myocardium in swine. Circ Res 43:652–661
Liedtke AJ, Demaison L, Eggleston, A, Cohen LM, Nellis SH (1988) Changes in substrate metabolism and effects of excess fatty acids in reperfused myocardium Circ Res 62:535–542
Lopaschuk GD, Spafford MA, Davies NJ, Wall SR (1990) Glucose and palmitate oxidation in isolated working rat hearts reperfused after a period of transient global ischemia. Circ Res 66:546–553
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Miyata H, Lakatta EG, Stern MD, Silverman HS (1992) Relation of mitochondrial and cytosolic free calcium to cardiac myocyte recovery after exposure to anoxia. Circ Res 71:605–613
Murphy ML, Peng CF, Kane JJ, Straub JD (1982) Ventricular performance and biochemical alteration of regional ischemic myocardium after reperfusion in the pig. Am J Cardiol 50:821–828
Nellis SH, Liedtke AJ, Renstrom B (1991) Distribution of carbon flux within fatty acid utilization during myocardial ischemia and reperfusion. Cric Res 69:779–790
Neely JR, Leibermeister H, Battersby EJ, Morgan HE (1967) Effect of pressure development on oxygen consumption by isolated rat heart. Am J Physiol 212:804–814
Palmer JW, Tandler B, Hoppel CL (1977) Biochemical properties of subsarcolemmal and interfibrillar mitochondria isolated from rat cardiac muscle. J Biol Chem 252:8731–8739
Palmer JW, Tandler B, Hoppel CL (1986) Heterogenous response of subsarcolemmal heart mitochondria to calcium. Am J Physiol 250:H741–H748
Peng CF, Davis JL, Murphy ML, Straub KD (1986) Effects of reperfusion on myocardial wall thickness, oxidative phosphorylation, and Ca2+metabolism following total and partial myocardial ischemia. Am Heart J 112:1238–244
Pennington RJ (1961) Determination of succinate dehydrogenase activity by use of 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyltetrazolium chloride as substate. Biochem J 80:649–654
Perry SV (1954) Creatine phosphokinase and the enzymic and contractile properties of the isolated myofibril. Biochem. 57:427–434
Reibel DK, Rovetto Mj (1978) Myocardial ATP synthesis and mechanical function following oxygen defficiency. Am J Physiol 234:H620–H624
Schaper W, Binz K, Sass S, Winkler B (1987) Influenceof collateral blood flow and of variations in MVO2 on tissue-ATP content in ischemic and infarcted myocardium. J Mol Cell Cardiol 19:19–37
Schwaiger M, Schelbert HR, Ellison D, Hansen, H, Yeatman L, Vinten-Johansen J, Selin C, Barrio J, Phelps ME (1985a) Sustained regional abnormalities in cardiac metabolism after transient ischemia in the chronic dog model. J Am Coll Cardiol 6:336–347
Schwaiger M, Schelbert HR, Keen R, Vinten-Johansen J, Hansen H, Selin C, Barri OJ, Huang SC, Phelps ME (1985b) Retention and clearance of C-11 palmitic acid in ischemic and reperfused canine myocardium. J Am Coll Cardiol 6:311–320
Schwaiger M, Neese RA, Arauyo L, Wyns W, Wineski JA, Sochor H, Swank S, Kulber D, Selin C, Phelps ME, Schelbert HR, Fishbein MC (1989) Sustained non oxidative glucose utilization and depletion of glycogen in reperfused canine myocardium. J Am Coll Cardiol 13:745–754
Sordhal LA, Johnson C, Blailock ZR, Schwartz, Schwartz A (1971) The mitochondrium. Methods of pharmocology. Chapter 8. Schwartz A ed
Steenbergen C, Murphy E, Levy L, London RE (1987) Elevation in cytosolic free calcium concentration early in myocardial ischemia in perfused rat heart. Circ Res 60:700–707
Van Bilsen M, van der Vusse GJ, Coumans WA, De Groot MJM, Willemsen HM, Reneman RS (1989) Degradation of adenine nucleotides in ischemic and reperfused rat heart. Am J Physiol 257:H47–H54
Zimmer SD, Ugurbil K, Michurski SP, Mohanakrishman, P, Ulstad VK, Foker JE, From AHL (1989) Alterations in oxidative function and respiratory regulation in the psot-ischemic myocardium. J Biol Chem 264:12402–12411
Zoratti M, Szabo I (1992) Channels and currents of the inner mitochondrial membrane. Trends Biomembr Bioenerg 1:263–329
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Demaison, L., Grynberg, A. Cellular and mitochondrial energy metabolism in the stunned myocardium. Basic Res Cardiol 89, 293–307 (1994). https://doi.org/10.1007/BF00795199
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DOI: https://doi.org/10.1007/BF00795199