ALPHA(1)-ADRENERGIC BLOCKADE REDUCES EXERCISE-INDUCED REGIONAL MYOCARDIAL-ISCHEMIA IN DOGS

The effect of selective alpha1-adrenoceptor blockade on regional myoca rdial blood flow and contractile function during exercise-induced myoc ardial ischemia was determined in nine dogs having chronic single vess el coronary stenosis (ameroid constrictor). Treadmill exercise perform ed after beta-adrenoceptor blockade (1.0 mg/kg i.v. propranolol), to b lock potential prejunctional effects recently recognized with alpha-bl ockade, elicited severe regional myocardial ischemia with a steady-sta te 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 i schemic subendocardium was reduced from 0.76 to 0.36 ml/min/g (microsp heres). Prazosin (80 mug/kg i.v.) was administered during continued ru nning, and angiotensin II was simultaneously infused to prevent the de crease in systemic arterial pressure caused by prazosin. During the su bsequent steady state, with arterial pressure matched to the pre-prazo sin level, regional subendocardial blood flow improved to 0.60 ml/min/ g and systolic wall thickening in the post-stenotic region increased m odestly 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 p razosin caused no effect on regional function in the control area, ind icating effective blockade of prejunctional effects of prazosin (demon strated in pilot studies). The finding that blockade of alpha1-adrenoc eptors resulted in improved ischemic zone subendocardial blood flow an d contractile function are consistent with alpha1-adrenoceptor-mediate d reduction of blood flow to the ischemic subendocardium during exerci se-induced ischemia in dogs with beta-blockade.