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Sarcolemmal integrity and metabolic competence of cardiomyocytes under anoxia-reoxygenation
J Moi
Cell
Cardiol21
(Supplement
IV) (1989)
FC22
STUNNING ENRANCES REGIONAL METABOLIC RECOVERY FOLLOWING 60' OF CORONARY OCCLUSION IN Max-Planck-Institute, Bad NauPIGS. R. Schott, E. Braun, S. Rohmann, W. Schaper. heim, F. R. Germany We have observed that infarct size is reduced following coronary occlusion (TCO) in swine myocardium stunned with brief episodes of ischemia. To study metabolic recovery we stunned swine (PRRCON) with 2 cycles of 10'TCO followed with 30' of reperfusion (REP), followed by 60' of TCO and 90' REP. Controls received only 60' TCO REP was reflected by A's in end-diastolic followed by 90' REP. Edema during the 90' Following 90' REP we biopwall thickness (EDWT) measured with ultrasonic crystals. sied ischemic regions for creatine phosphate (CP) and ATP. Risk region (RR) was measured with fluorescein and infarct size (XIR) as X of RR was determined after incubaXARDWT (EDWT/Control EDWT): tion with p-NBT. Results*SM: 60'REPX cp* ATP RR XIR* 1S'REP 30'REP PRECON 33.8f2.1 5.5fO.l 14.2f1.3 9.2f5.7 125.7f 7.5 107.4f15.1 106.6f 6.8** 140.0f12.3 145.6f18.1 142.1f12.7 CONTROLS 13.2f3.1 4.0f0.9 14.6f1.9 48.0f12.7 *(p<.Ol t-test, ATPbCP in ng/mg dry wt) 'ANOVA p-.05. **p-.01 vs. 15'REP. We conclude that ischemic preconditioning reduces infarct size following 60' of LAD TCO in pigs, and that the ischemic region demonstrates the ability to restore CP. Early resolution of reperfusion edema indicates preservation of cellular integritry despite the additional 20' of ischemia in preconditioned myocardium.
FC23
CARDIAC WORK IS NOT UNIFORMLY RELATED TO CYTOSOLIC ADP CONCENTRATION AND PHOSPHOHYLATJON POTENTIAL. V.V.Kupriyanov. A.Ya.Steinschneider. V.L.Lakomkin. V.I.Kapelko. V.A.Saks. USSR Cardiology Research Centre. Moscow. USSR. Changes in cytosolic [ADP] and phosphorylation potegijal (PP) were calculated from [PCrl/[Cr] ratio, [ATPI and [Pi] determined from P-NMR spectra and creatine kinase ICK) equilibrium in isovolumic hearts perfused with 5 mM pyruvate related to the increase in cardiac work (PRP=pressure-rate product). A rise of PRP induced by an increase in coronary flow (CF) rate (from 13 to 25 ml/min*g wet wt) resulted in some increase in PP and decrease-jn free [ADP]. In contrast, elevation 0f PRP induced by isoproterenol (Iso. 10 M) administration at moderate CF (13 ml/g wet wt) was followed by oppositely directed changes: decrease in PP and augmentation of cytosolir LADP]. Furthermore, in CK-inhibited (99%, by iodoacetamide) and adenine nucleotide depleted (by 70%, 2-deoxyglucose treament) [ADP] was 2.5 times higher and 2 times lower. respectively, in comparison with the control at the same PRP values. Thus. neither cytosolic [ADP]. nor PP can be considered as a sole control parame er Ca 8+ of energy turnover in the heart. Other possjble control points such as. e.g.. dependent mitochondrial dehydrogenases and tissue oxygen delivery as well as ndpnine nucleotides compartmentntion have to be taken into account to provide adequatr description of complex mechanism of energy turnover regulation.
Fc24
SARCOLEMMAL INTEGRITY AND METABOLIC COMPETENCE OF CARDIOMYOCYTES UNDER ANOXIA-REOXYGENATION. B. Siegmund, A. T. Klietz, H.M. Piper. KOOP, Physiologisches Institut I, Universitzt Diisseldorf, FRG In tissue, mechanical cell-cell interactions may contribute to cardiomyocyte injury in anoxia-reoxygenation. In the present study, the disturbance of energy metabolism and cell injury were investigated in isolated cardiomyocytes, free of external mechanical constraints. Cardiomyocytes from adult rat, attached to culture dishes, were exposed to 120 min anoxia and 15 min reoxygenation in a substrate-free modified Tyrode solution. The energetic state of the cells in anoxia-reoxygenation was characterized by the free energy change of ATP hydrolysis amounting to 51 kJ/mol ATP in normoxia. After 120 min anoxia (*GATP), all cells were contracted to 65 % of their length and *GATp decreased to 41 kJ/mol. No lactate dehydrogenase was released. Reoxygenation caused a partial oxygen paradox: immediate hypercontracture of the cells, but no release of lactate dehydrogenase. -GATp recovered to 51 kJ/mol within 15 min. The results demonstrate that anoxic cardiomyocytes can be energydepleted without losing sarcolemmal integrity. They can undergo hypercontracture, elicited by reoxygenation, and yet re-establish a normal energetic state. (Supported by the DFG, Pi 162/2-l) S.67
Cell
Cardiol21
(Supplement
IV) (1989)
FC22
STUNNING ENRANCES REGIONAL METABOLIC RECOVERY FOLLOWING 60' OF CORONARY OCCLUSION IN Max-Planck-Institute, Bad NauPIGS. R. Schott, E. Braun, S. Rohmann, W. Schaper. heim, F. R. Germany We have observed that infarct size is reduced following coronary occlusion (TCO) in swine myocardium stunned with brief episodes of ischemia. To study metabolic recovery we stunned swine (PRRCON) with 2 cycles of 10'TCO followed with 30' of reperfusion (REP), followed by 60' of TCO and 90' REP. Controls received only 60' TCO REP was reflected by A's in end-diastolic followed by 90' REP. Edema during the 90' Following 90' REP we biopwall thickness (EDWT) measured with ultrasonic crystals. sied ischemic regions for creatine phosphate (CP) and ATP. Risk region (RR) was measured with fluorescein and infarct size (XIR) as X of RR was determined after incubaXARDWT (EDWT/Control EDWT): tion with p-NBT. Results*SM: 60'REPX cp* ATP RR XIR* 1S'REP 30'REP PRECON 33.8f2.1 5.5fO.l 14.2f1.3 9.2f5.7 125.7f 7.5 107.4f15.1 106.6f 6.8** 140.0f12.3 145.6f18.1 142.1f12.7 CONTROLS 13.2f3.1 4.0f0.9 14.6f1.9 48.0f12.7 *(p<.Ol t-test, ATPbCP in ng/mg dry wt) 'ANOVA p-.05. **p-.01 vs. 15'REP. We conclude that ischemic preconditioning reduces infarct size following 60' of LAD TCO in pigs, and that the ischemic region demonstrates the ability to restore CP. Early resolution of reperfusion edema indicates preservation of cellular integritry despite the additional 20' of ischemia in preconditioned myocardium.
FC23
CARDIAC WORK IS NOT UNIFORMLY RELATED TO CYTOSOLIC ADP CONCENTRATION AND PHOSPHOHYLATJON POTENTIAL. V.V.Kupriyanov. A.Ya.Steinschneider. V.L.Lakomkin. V.I.Kapelko. V.A.Saks. USSR Cardiology Research Centre. Moscow. USSR. Changes in cytosolic [ADP] and phosphorylation potegijal (PP) were calculated from [PCrl/[Cr] ratio, [ATPI and [Pi] determined from P-NMR spectra and creatine kinase ICK) equilibrium in isovolumic hearts perfused with 5 mM pyruvate related to the increase in cardiac work (PRP=pressure-rate product). A rise of PRP induced by an increase in coronary flow (CF) rate (from 13 to 25 ml/min*g wet wt) resulted in some increase in PP and decrease-jn free [ADP]. In contrast, elevation 0f PRP induced by isoproterenol (Iso. 10 M) administration at moderate CF (13 ml/g wet wt) was followed by oppositely directed changes: decrease in PP and augmentation of cytosolir LADP]. Furthermore, in CK-inhibited (99%, by iodoacetamide) and adenine nucleotide depleted (by 70%, 2-deoxyglucose treament) [ADP] was 2.5 times higher and 2 times lower. respectively, in comparison with the control at the same PRP values. Thus. neither cytosolic [ADP]. nor PP can be considered as a sole control parame er Ca 8+ of energy turnover in the heart. Other possjble control points such as. e.g.. dependent mitochondrial dehydrogenases and tissue oxygen delivery as well as ndpnine nucleotides compartmentntion have to be taken into account to provide adequatr description of complex mechanism of energy turnover regulation.
Fc24
SARCOLEMMAL INTEGRITY AND METABOLIC COMPETENCE OF CARDIOMYOCYTES UNDER ANOXIA-REOXYGENATION. B. Siegmund, A. T. Klietz, H.M. Piper. KOOP, Physiologisches Institut I, Universitzt Diisseldorf, FRG In tissue, mechanical cell-cell interactions may contribute to cardiomyocyte injury in anoxia-reoxygenation. In the present study, the disturbance of energy metabolism and cell injury were investigated in isolated cardiomyocytes, free of external mechanical constraints. Cardiomyocytes from adult rat, attached to culture dishes, were exposed to 120 min anoxia and 15 min reoxygenation in a substrate-free modified Tyrode solution. The energetic state of the cells in anoxia-reoxygenation was characterized by the free energy change of ATP hydrolysis amounting to 51 kJ/mol ATP in normoxia. After 120 min anoxia (*GATP), all cells were contracted to 65 % of their length and *GATp decreased to 41 kJ/mol. No lactate dehydrogenase was released. Reoxygenation caused a partial oxygen paradox: immediate hypercontracture of the cells, but no release of lactate dehydrogenase. -GATp recovered to 51 kJ/mol within 15 min. The results demonstrate that anoxic cardiomyocytes can be energydepleted without losing sarcolemmal integrity. They can undergo hypercontracture, elicited by reoxygenation, and yet re-establish a normal energetic state. (Supported by the DFG, Pi 162/2-l) S.67