Selective manipulation of neurohumoral control of the cardiac pacemaker by drugs given intrapericardially

A technique of intrapericardial administration of beta-adrenoceptor and muscarinic cholinergic receptor antagonist drugs has been tested in conscious rabbits. Intrapericardial propranolol or atenolol (50 micrograms/kg) had the same effect on isoprenaline heart rate dose-response curves and on the sympathetic component of the arterial baroreceptor-heart rate reflex as did conventional, 5-fold greater, intravenous doses of the drugs. The action of intrapericardial propranolol was attributable to its (-)isomer. Intrapericardial propranolol (50 micrograms/kg) had little effect on ventricular contractility. Plasma levels of propranolol and atenolol after intrapericardial administration were, respectively, 7- and 40-fold less than after the usual intravenous doses. Intrapericardial hyoscine methyl bromide (10 micrograms/kg) abolished baroreflex vagal effects on heart rate as effectively as did the conventional, 5-fold greater, intravenous dose. The duration of receptor blockade by both classes of drugs when given intrapericardially was at least 2 hr. We conclude that the rapid diffusion of beta-adrenoceptor and muscarinic cholinergic receptor blocking drugs from the pericardial sac to receptors on the sinoatrial cardiac pacemaker, and their prolonged actions, provides a useful technique for preventing the actions of the sympathetic and vagus nerves, and of circulating catecholamines, on the chronotropic functions of the heart.