Sympathetic Mechanisms in Poststenotic Myocardial Ischemia

Abstract

A coronary stenosis can be compensated by dilation of the poststenotic vascular bed. Activation of cardiac sympathetic nerves can disturb this balance. Experiments in anesthetized, vagotomized dogs revealed that electrical stimulation of cardiac sympathetic nerves as well as reflex sympathetic activation by bilateral carotid occlusion induce vasoconstriction distal to severe coronary stenoses, which were defined by the lack of any postocclusive reactive hyperemia. The poststenotic vasoconstriction is mediated by alpha 2-adrenoceptors and, in concert with the beta-adrenoceptor mediated increase in myocardial oxygen demand, it induces an acute ischemia of the poststenotic myocardium. This ischemia was evidenced by contractile dysfunction, net lactate production, the occurrence of ventricular fibrillation in 10% of dogs, and the development of subendocardial necroses after repetitive sympathetic stimulation. The alpha-antagonist phentolamine, the selective alpha 2-antagonist rauwolscine, and the calcium antagonist nifedipine prevent both poststenotic vasoconstriction and ischemia, whereas the beta-antagonist propranolol enhances even poststenotic vasoconstriction, but still prevents ischemia. Poststenotic ischemia can thus result from sympathetic activation but, in turn, also activates cardiac sympathetic nerves by a spinal reflex. This positive feedback provides a basis for a progressive poststenotic vasoconstriction and aggravation of myocardial ischemia. This vicious cycle can be interrupted by rauwolscine and nifedipine, as well as by segmental epidural anesthesia with procaine at segments C6-T7. The poststenotic ischemia induced by sympathoexcitatory reflexes can also be prevented by blocking the sympathoexcitation at the central nervous level by clonidine. Our studies emphasize the role of cardiac sympathetic nerves and alpha 2-mediated poststenotic vasoconstriction in the genesis and aggravation of poststenotic myocardial ischemia.