Pharmacological mechanisms to attenuate sympathetically induced myocardial ischemia.

Distal to a coronary stenosis, resting myocardial blood flow and function can be maintained by a compensatory dilation of the poststenotic vascular bed and an increased collateral blood flow from adjacent coronary vessels. Under this condition, electrical stimulation of cardiac sympathetic nerves, as well as their activation during sympathoexcitatory reflexes and exercise, induces a poststenotic alpha 2-adrenoceptor-mediated coronary constriction and a beta-adrenoceptor-mediated, tachycardia-related redistribution of blood flow away from the ischemia myocardium. Thus, activation of cardiac sympathetic nerves can precipitate poststenotic myocardial ischemia. In experimental studies in anesthetized, vagotomized dogs, as well as in conscious, chronically instrumented dogs, selective alpha 2-adrenoceptor antagonists and calcium-channel blockade with nifedipine were able to attenuate the sympathetically induced poststenotic myocardial ischemia. Beta-adrenoceptor blockade with atenolol was only proven beneficial as long as there was a heart-rate reduction. Conversely, a specific bradycardic agent (ULFS-49) also exerted beneficial effects. Myocardial ischemia can activate cardiac sympathetic afferents and then, by a spinal reflex, can in turn activate sympathetic efferents and aggravate the severity of myocardial ischemia. This vicious cycle could be interrupted by segmental epidural anesthesia with procaine as well as by blockade of sympathoexcitation at the central nervous level with clonidine in anesthetized dogs.