Alpha 1-adrenergic blockade reduces exercise-induced regional myocardial ischemia in dogs

The effect of selective alpha 1-adrenoceptor blockade on regional myocardial blood flow and contractile function during exercise-induced myocardial ischemia was determined in nine dogs having chronic single vessel coronary stenosis (ameroid constrictor). Treadmill exercise performed after beta-adrenoceptor blockade (1.0 mg/kg i.v. propranolol), to block potential prejunctional effects recently recognized with alpha-blockade, elicited severe regional myocardial ischemia with a steady-state reduction of regional systolic wall thickening of the post-stenotic myocardium from a resting value of 21.8% to 7.0%. Blood flow to the ischemic subendocardium was reduced from 0.76 to 0.36 ml/min/g (microspheres). Prazosin (80 micrograms/kg i.v.) was administered during continued running, and angiotensin II was simultaneously infused to prevent the decrease in systemic arterial pressure caused by prazosin. During the subsequent steady state, with arterial pressure matched to the pre-prazosin level, regional subendocardial blood flow improved to 0.60 ml/min/g and systolic wall thickening in the post-stenotic region increased modestly to 10.2%. No changes in blood flow to the outer portion of the post-stenotic region or to the remote control region were seen, and prazosin caused no effect on regional function in the control area, indicating effective blockade of prejunctional effects of prazosin (demonstrated in pilot studies). The finding that blockade of alpha 1-adrenoceptors resulted in improved ischemic zone subendocardial blood flow and contractile function are consistent with alpha 1-adrenoceptor-mediated reduction of blood flow to the ischemic subendocardium during exercise-induced ischemia in dogs with beta-blockade.