Role of beta-adrenoreceptor antagonism in the prevention of reperfusion ventricular arrhythmias: effects of acebutolol, atenolol, and d-propranolol on isolated working rat hearts subject to myocardial ischemia and reperfusion.
The role of catecholamines in the genesis of ventricular arrhythmias during the reperfusion period following coronary occlusion remains incompletely understood. An isolated rat heart preparation, free from the influence of autonomic innervation or of circulating catecholamines, was used to assess the effects of beta-adrenoceptor blockade. The hearts were prelabeled with tritiated norepinephrine ( NE3H ), and the total radioactivity and that in NE3H were measured in the effluent coronary flow. The left main coronary artery was ligated for 10 minutes after which reperfusion followed. The liberation of NE3H and the development of ventricular tachycardia and fibrillation were monitored throughout. The cardioselective beta-antagonist agent, acebutolol, in a high concentration (1.1 X 10(-4)M), had good beta-antagonist effect in response to the added isoproterenol (10(-6)M); this concentration of acebutolol also suppressed sustained reperfusion ventricular arrhythmias but unexpectedly increased the release of NE3H . Atenolol, another cardioselective agent, did not prevent reperfusion ventricular arrhythmias even in a high concentration of 40 mg/L (1.5 X 10(-4)M). The d-isomer of propranolol, with poorer beta-antagonist properties than the l-isomer, prevented such ventricular arrhythmias in a concentration of 1.3 X 10(-5)M, which was low when compared to that of atenolol. It is proposed that the beta-antagonist activity of the compounds tested could not explain the inhibition of reperfusion ventricular arrhythmias and that another quality such as membrane-stabilizing activity may be involved.
D000070:Acebutolol / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D001262:Atenolol / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000473:pathology*; D009638:Norepinephrine / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D000319:Adrenergic beta-Antagonists; D014316:Tritium; D001262:Atenolol; D000070:Acebutolol; D011433:Propranolol; D009638:Norepinephrine