Cardioprotective and antidysrhythmic effects of alpha 1-adrenoceptor blockade during myocardial ischaemia and reperfusion in the dog.

Recent research in cats suggests that cardiac alpha 1-adrenoceptors are involved in the genesis of early life threatening ventricular dysrhythmias following myocardial infarction. Evidence for the existence of cardiac alpha 1-adrenoceptors has been obtained in all the mammalian species investigated to date and includes guinea pig, rabbit, cat, dog, rat and humans. The present series of experiments was conducted in dogs, a species in which reperfusion is associated with higher mortality than the cat. It was found that alpha-adrenoceptor block with prazosin significantly reduced ventricular ectopic activity during coronary artery occlusion and reperfusion and reduced mortality associated with reperfusion. To ascertain the site of action of prazosin and other alpha 1-adrenoceptor antagonists in this context it is necessary to consider their effects on haemodynamics, the coronary vasculature and the myocardium. Prazosin and related alpha 1-adrenoceptor antagonists have been shown to be extremely effective in abrogating catecholamine induced ventricular arrhythmias in the dog and are additive with beta-adrenoceptor antagonists in this respect. However, in the present experiments prazosin caused a significant attenuation of the repayment of coronary flow debt on reperfusion, reduced the ischaemia induced rise in filling pressure and increased coronary blood flow during coronary artery occlusion. Thus, whether the beneficial effects of alpha 1-adrenoceptor blockade are solely the result of blockade of myocardial alpha 1-adrenoceptors and not, at least in part, improved coronary blood flow within the ischaemic bed requires further study.