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Prevention of regional myocardial ischemia by different calcium entry blockers
j Mol Cell Cardiol 19 (Supplement III) (1987)
133
INTRACORONARY SUPEROXIDE DISMUTASE FOR THE TREATMENT OF "REPERFUSION INJURY" H.H. Klein, S. Pich, S. Lindert, A. Buchwald, K. Nebendahl, H. Kreuzer. Dept. of Cardiology, University of G0ttingen, FRG The effect o f recombinant human superoxide dismutase (rh-SOD) on the infarct size was investigated in porcine hearts. The left anterior descending coronary artery was occluded in each of 24 anesthetized pigs for 45 min and was reperfused for 24 h. Infarct size was determined as the ratio of the infarcted myocardium (tetrazolium stain) to the risk region (dye-technique). The animals were randomly assigned to either rh-SOD (n=12) or placebo treatment (n=I2). Two minutes before reperfusion an intracoronary (ic) infusion of rh-SOD (total dose 2000 U/kg) or placebo was started which lasted for 47 min. IC rh-SOD treatment during reperfusion did not reduce infarct size significantly. Infarct size amounted to 74+13 % in the control group and to 66+19 % in the treated group. The incidence of re-perfusion arrhythmias was not affected by rh-SOD treatment. Conclusion: Ic rh-SOD treatment at the beginning of reperfusion does neither reduce infarct size nor diminish the incidence of reperfusion arrhythmias in this preparation.
134
COMPARATIVE STUDY ON THE ENHANCEMENT OF ISCHEMIC TOLERANCE BY INTRACORONARY PRETREATMENT WITH THREE CALCIUM ANTAGONISTS IN PIG HEARTS H.H. Klein, S. Pich, S. Lindert, K. Nebendahl, A. Buchwald, H. Kreuzer. Dept. of Cardiology, University of GSttingen, FRG The effect of intracoronary (ic) pretreatment with diltiazem (4 mg/2 rain), nifedipine (0.4 mg/2 rain), and verapamiI (i mg/2 min) on infarct size after transient ischemia was investigated in three experimental series including 5] pigs. Infarct size was determined as percentage of the infarcted myoeardium (tetrazollum stain) over the risk region (dye technique) after transient ischemia of 45-90 rain and reperfusion of 24 h. In series I ic diltiazem administered at the time of occlusion increased ischemic tolerance by more than 50 % compared to controls. In series II the effect of ic pretreatment with the three calcium antagonists on infarct size was compared after 75 min of transient ischemia. The smallest infarctions were observed in the verapamil group followed by di]tiazem and nifedipine groups. In series Ill ischemia was initiated for 45 rain eight minutes after ic treatment. In contrast to diltiazem and nifedipine verapamiI still exhibited a pronounced protective effect. Conclusion: A t equidepressant ic doses verapamiI protects the ischemic myocardium to a greater extent than diitiazem or nifedipine.
135
PREVENTION OF REGIONAL MYOCARDIAL ISCHEM{A BY DIFFERENT CALCIUM ENTRY BLOCKERS. B. Kleuren, A. Heider, S. Dhein, W. Klaus, R. R6sen. Pharmacol. Institute, University of Cologne, Cologne, FRG. The aim of this study was to examine the potency of different calcium-antagonists (CA) to protect against ischemic damage, when applicated before coronary occlusion. In Langendorff-perfused rabbit hearts the epicardial ischemic area was quantified by image analysis from NADH - fluorescence photographies. To determine the ventricular area provided by the vessel to be ligated a reversible test-occlusion for 10 min (LIGI) was performed, followed by 60 min of reperfusion. Ths a permanent ligation (LIG2) was set at the same position for further 60 min. Perfusion with either nifedipine (NIF, 5 nmol/l; n = 6), nitrendipine (NIT, 5 nmol/l; n = 6), or verapamil (VER, 40 nmol/l; n = 5) was started during the reperfusion period, 30 min before onset of LIG2, and continued for 90 min. The perfusion with CA induced the following alterations of coronary flow (CF) and left-ventricular-pressure (LVP): NIF and NIT (+ 15% CF; - 12% LVP), VER (• 0% CF; - 30% LVP). Upon LIG2 in the untreated control group (n = 6) the size of ischemic area (105 Z 9%) was not significantly different when compared to LIGI (100%). All CA induced a significant decrease of total epicardial ischemic area 60 min after onset of LIG2 in succession: NIF (38 • 5%), NIT (53 • 12%) and VER (68 Z 8%). Since VER, in contrast to NIF or NIT, did not increase the total coronary flow rate, the diminution of an ischemic area might not exclusively depend on an improvement of regional perfusion. - Supported by DFG Ro 557/1
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133
INTRACORONARY SUPEROXIDE DISMUTASE FOR THE TREATMENT OF "REPERFUSION INJURY" H.H. Klein, S. Pich, S. Lindert, A. Buchwald, K. Nebendahl, H. Kreuzer. Dept. of Cardiology, University of G0ttingen, FRG The effect o f recombinant human superoxide dismutase (rh-SOD) on the infarct size was investigated in porcine hearts. The left anterior descending coronary artery was occluded in each of 24 anesthetized pigs for 45 min and was reperfused for 24 h. Infarct size was determined as the ratio of the infarcted myocardium (tetrazolium stain) to the risk region (dye-technique). The animals were randomly assigned to either rh-SOD (n=12) or placebo treatment (n=I2). Two minutes before reperfusion an intracoronary (ic) infusion of rh-SOD (total dose 2000 U/kg) or placebo was started which lasted for 47 min. IC rh-SOD treatment during reperfusion did not reduce infarct size significantly. Infarct size amounted to 74+13 % in the control group and to 66+19 % in the treated group. The incidence of re-perfusion arrhythmias was not affected by rh-SOD treatment. Conclusion: Ic rh-SOD treatment at the beginning of reperfusion does neither reduce infarct size nor diminish the incidence of reperfusion arrhythmias in this preparation.
134
COMPARATIVE STUDY ON THE ENHANCEMENT OF ISCHEMIC TOLERANCE BY INTRACORONARY PRETREATMENT WITH THREE CALCIUM ANTAGONISTS IN PIG HEARTS H.H. Klein, S. Pich, S. Lindert, K. Nebendahl, A. Buchwald, H. Kreuzer. Dept. of Cardiology, University of GSttingen, FRG The effect of intracoronary (ic) pretreatment with diltiazem (4 mg/2 rain), nifedipine (0.4 mg/2 rain), and verapamiI (i mg/2 min) on infarct size after transient ischemia was investigated in three experimental series including 5] pigs. Infarct size was determined as percentage of the infarcted myoeardium (tetrazollum stain) over the risk region (dye technique) after transient ischemia of 45-90 rain and reperfusion of 24 h. In series I ic diltiazem administered at the time of occlusion increased ischemic tolerance by more than 50 % compared to controls. In series II the effect of ic pretreatment with the three calcium antagonists on infarct size was compared after 75 min of transient ischemia. The smallest infarctions were observed in the verapamil group followed by di]tiazem and nifedipine groups. In series Ill ischemia was initiated for 45 rain eight minutes after ic treatment. In contrast to diltiazem and nifedipine verapamiI still exhibited a pronounced protective effect. Conclusion: A t equidepressant ic doses verapamiI protects the ischemic myocardium to a greater extent than diitiazem or nifedipine.
135
PREVENTION OF REGIONAL MYOCARDIAL ISCHEM{A BY DIFFERENT CALCIUM ENTRY BLOCKERS. B. Kleuren, A. Heider, S. Dhein, W. Klaus, R. R6sen. Pharmacol. Institute, University of Cologne, Cologne, FRG. The aim of this study was to examine the potency of different calcium-antagonists (CA) to protect against ischemic damage, when applicated before coronary occlusion. In Langendorff-perfused rabbit hearts the epicardial ischemic area was quantified by image analysis from NADH - fluorescence photographies. To determine the ventricular area provided by the vessel to be ligated a reversible test-occlusion for 10 min (LIGI) was performed, followed by 60 min of reperfusion. Ths a permanent ligation (LIG2) was set at the same position for further 60 min. Perfusion with either nifedipine (NIF, 5 nmol/l; n = 6), nitrendipine (NIT, 5 nmol/l; n = 6), or verapamil (VER, 40 nmol/l; n = 5) was started during the reperfusion period, 30 min before onset of LIG2, and continued for 90 min. The perfusion with CA induced the following alterations of coronary flow (CF) and left-ventricular-pressure (LVP): NIF and NIT (+ 15% CF; - 12% LVP), VER (• 0% CF; - 30% LVP). Upon LIG2 in the untreated control group (n = 6) the size of ischemic area (105 Z 9%) was not significantly different when compared to LIGI (100%). All CA induced a significant decrease of total epicardial ischemic area 60 min after onset of LIG2 in succession: NIF (38 • 5%), NIT (53 • 12%) and VER (68 Z 8%). Since VER, in contrast to NIF or NIT, did not increase the total coronary flow rate, the diminution of an ischemic area might not exclusively depend on an improvement of regional perfusion. - Supported by DFG Ro 557/1
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