Calcium antagonists, ventricular fibrillation, and enzyme release in ischemic rat hearts.
Early experiments with the calcium antagonist verapamil showed that it could inhibit the transsarcolemmal influx of calcium ions induced by isoproterenol in ventricular myocardium without inhibiting the effect of beta stimulation to increase tissue cyclic AMP. Current views of the effects of the beta-receptor-adenylate cyclase-cyclic AMP system of the calcium channel suggest that both calcium antagonists and beta-adrenoceptor antagonists should inhibit transsarcolemmal calcium influx if calcium is the third messenger of beta-agonist catecholamines. When high concentrations of circulating catecholamines are added to normal isolated hearts, two of the effects include increased vulnerability to ventricular fibrillation and high rates of enzyme release. These effects are antagonized by beta-adrenoceptor inhibitors and by calcium antagonists, which suggests a classical second (cyclic AMP) and third (calcium) messenger effect. In the presence of coronary artery ligation, the ventricular fibrillation threshold falls and enzyme release is enhanced. Both effects are associated with an increased tissue cyclic AMP level in the ischemic zone and are susceptible to calcium antagonist procedures. Neither effect can be fully stopped by beta-adrenoceptor antagonism. Therefore the evidence from this model with coronary artery ligation favors the views that 1) cyclic AMP accumulates in ischemic tissue by a process not fully susceptible to inhibition by beta-adrenoceptor antagonists; and 2) calcium ions are associated with the development of ventricular fibrillation and enzyme release by a process susceptible to inhibition by calcium antagonist agents such as verapamil, nifedipine, and diltiazem.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003327:Coronary Disease / Q000201:enzymology*; D003331:Coronary Vessels; D000242:Cyclic AMP / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D008026:Ligation; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D014693:Ventricular Fibrillation / Q000201:enzymology*
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D000242:Cyclic AMP; D004837:Epinephrine