This study initially investigated the effects of extracellular calcium on the metabolism of cyclic AMP and cyclic GMP in the isolated perfused hearts of rats and rabbits. Calcium produced concentration-related changes in cyclic nucleotide levels, although the mechanisms of these observations were not elucidated. However, the study illustrated the complexities of the metabolic control of cyclic nucleotide levels. The interactions of calcium and cyclic nucleotides on the electrical stability of the myocardium were then investigated using ventricular fibrillation threshold determinations in isolated rat hearts. Fibrillation thresholds were found to be dependent on the calcium concentration of the perfusate and changed independently of cyclic AMP levels. A number of other interventions, which may relate to arrhythmia production or anti-arrhythmic therapy, also produced changes in fibrillation thresholds which were not dependent on the myocardial content of cyclic AMP. The influence of ionic milieu was studied in a model of ventricular arrhythmias which involved ligation of the main left coronary artery of the isolated rat heart. During ligation, arrhythmias occurred in a solution containing a low potassium and a high calcium concentration. It was demonstrated that these ischaemia-induced ventricular arrhythmias did not appear to be influenced by adrenergic mechanisms inherent in the myocardium.
|Date of Award||1981|