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Antagonism by exogenous adenosine of arrhythmogenesis in the coronary-ligated isolated perfused rat heart
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THE TEMPERATURE DEPENDENCE OF THE RATE OF OXYGEN CONSUMPTION OF THE Monash University, QUIESCENT ISOLATED RABBIT HEART. D.S. Loiselle, Australia; currently: Department of Physiology, University of Auckland, New Zealand. Hearts of adult rabbits were mounted in a Langendorff apparatus. The coronary circulation was back-perfused with normal (4.8mmol-R-l K') Krebs-Henseleit solution via the aortic (arterial) cannula in the A second (venous) cannula was placed via the pulmonary usual fashion. artery into the right ventricle to collect the coronary sinus drainage. Each heart was subjected to temperatures of 17, 27 and 37'C presented such that time-dependent effects could be separately analysed. At each temperature the heart was equilibrated for 30 min in normal perfusate; 45 min of cardiac arrest followed, achieved by raising K+ to 20 mmol.R-l. Eighteen hearts were studied, six under each of three conditions: constant (8 kPa) perfusion pressure - left ventricle vented, constant (14 mlvmin-l) perfusion rate - left ventricle vented, and constant perfusion rate - left ventricle intact. Coronary vascular resistance increased by 55 per 'C under esch perfusion condition. Oxygen consumption, given by the product of perfusion rate and the difference in oxygen content (Lexington 07 analyser) between arterial and venous samples J)erformed in triplicate, declined exponentially from 3.6 to 2.4 ml 02*g-l*min-1 over the 4 h period. There was no difference in the temperature dependence of oxygen consumption among the three perfusion conditions. The average QlD (1.25) although extremely low, is in general agreement with other in vitro measurements of cardiac basal metabolism. -___ ANTAGONISM BY EXOGENOUS ADENOSINE OF ARRHYTHMOGENESIS IN THE CORONARYLIGATED ISOLATED PERFUSED RAT HEART. Lubbe WF, Nguyen T and West EJ. Department of Medicine, Green Lane Hospital and University of Auckland, Auckland, New Zealand. In the isolated rat heart coronary artery ligation causes in ischaemic myocardium depletion of high energy phosphates and accumulation of lactate, cyclic adenosine monophosphate (CAMP), adenosine, inosine, hypoxanthine and xanthine. Concurrently, the ventricular fibrillation threshold (VFT) decreases and spontaneous arrhythmias develop (with ventricular fibrillation (VF) in 30%). When ischaemic tissue CAMP is increased further by inhibition of CAMP-phosphodiesterase using MIX (1-methyl,3-isobutyl xanthine, lo-50 umol/l) or by lowering of perfusate potassium concentration from 5.9 to 3.0 mmol/l, the VFT is reduced further and arrhythmias occur more frequently (VF in 80-100%) without alteration in high energy phosphate depletion or lactate accumulation. In such stimulated hearts, addition of adenosine (lo-500 pmol/l) to the perfusate causes a concentration-related reduction in arrhythmias (with 100 umol/l, VF in 10%). The antiarrhythmic effect of adenosine in low potassium and MIX stimulated hearts is not accompanied by a reduction in ischaemic tissue CAMP. Adenosine antagonizes arrhythmogenic mechanisms in the ischaemic rat heart independently of an influence on accumulation in ischaemic tissue of CAMP, a factor which increases vulnerability to fibrillation. (Supported by grants from the Medical Research Council and National Heart Foundation of New Zealand and the Auckland Medical Research Foundation.)
THE TEMPERATURE DEPENDENCE OF THE RATE OF OXYGEN CONSUMPTION OF THE Monash University, QUIESCENT ISOLATED RABBIT HEART. D.S. Loiselle, Australia; currently: Department of Physiology, University of Auckland, New Zealand. Hearts of adult rabbits were mounted in a Langendorff apparatus. The coronary circulation was back-perfused with normal (4.8mmol-R-l K') Krebs-Henseleit solution via the aortic (arterial) cannula in the A second (venous) cannula was placed via the pulmonary usual fashion. artery into the right ventricle to collect the coronary sinus drainage. Each heart was subjected to temperatures of 17, 27 and 37'C presented such that time-dependent effects could be separately analysed. At each temperature the heart was equilibrated for 30 min in normal perfusate; 45 min of cardiac arrest followed, achieved by raising K+ to 20 mmol.R-l. Eighteen hearts were studied, six under each of three conditions: constant (8 kPa) perfusion pressure - left ventricle vented, constant (14 mlvmin-l) perfusion rate - left ventricle vented, and constant perfusion rate - left ventricle intact. Coronary vascular resistance increased by 55 per 'C under esch perfusion condition. Oxygen consumption, given by the product of perfusion rate and the difference in oxygen content (Lexington 07 analyser) between arterial and venous samples J)erformed in triplicate, declined exponentially from 3.6 to 2.4 ml 02*g-l*min-1 over the 4 h period. There was no difference in the temperature dependence of oxygen consumption among the three perfusion conditions. The average QlD (1.25) although extremely low, is in general agreement with other in vitro measurements of cardiac basal metabolism. -___ ANTAGONISM BY EXOGENOUS ADENOSINE OF ARRHYTHMOGENESIS IN THE CORONARYLIGATED ISOLATED PERFUSED RAT HEART. Lubbe WF, Nguyen T and West EJ. Department of Medicine, Green Lane Hospital and University of Auckland, Auckland, New Zealand. In the isolated rat heart coronary artery ligation causes in ischaemic myocardium depletion of high energy phosphates and accumulation of lactate, cyclic adenosine monophosphate (CAMP), adenosine, inosine, hypoxanthine and xanthine. Concurrently, the ventricular fibrillation threshold (VFT) decreases and spontaneous arrhythmias develop (with ventricular fibrillation (VF) in 30%). When ischaemic tissue CAMP is increased further by inhibition of CAMP-phosphodiesterase using MIX (1-methyl,3-isobutyl xanthine, lo-50 umol/l) or by lowering of perfusate potassium concentration from 5.9 to 3.0 mmol/l, the VFT is reduced further and arrhythmias occur more frequently (VF in 80-100%) without alteration in high energy phosphate depletion or lactate accumulation. In such stimulated hearts, addition of adenosine (lo-500 pmol/l) to the perfusate causes a concentration-related reduction in arrhythmias (with 100 umol/l, VF in 10%). The antiarrhythmic effect of adenosine in low potassium and MIX stimulated hearts is not accompanied by a reduction in ischaemic tissue CAMP. Adenosine antagonizes arrhythmogenic mechanisms in the ischaemic rat heart independently of an influence on accumulation in ischaemic tissue of CAMP, a factor which increases vulnerability to fibrillation. (Supported by grants from the Medical Research Council and National Heart Foundation of New Zealand and the Auckland Medical Research Foundation.)