Progressive coronary vasoconstriction during relative ischemia in canine myocardium.

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Abstract
Under certain conditions, a progressive increase in vascular resistance occurs within ischemic myocardium during the first 3 h after coronary artery stenosis. The hypothesis that the increased resistance is due to local release of a vasoconstrictor substance in the ischemic region was tested. Relative ischemia was produced in anesthetized dogs by a combination of acute coronary arterial stenosis and increased myocardial metabolism. A hydraulic occluder on the left anterior descending coronary artery was adjusted to maintain distal left anterior descending coronary artery pressure at 50 mm Hg during atrial pacing at 180 beats/min. Myocardial blood flows were measured with 15-.mu.m microspheres after 30 and 180 min of relative ischemia. During this time, transmural left anterior descending coronary artery flow decreased by an average of 30%. Infusion of adenosine into the ischemic region after 180 min produced a 74 .+-. 17% increase in flow, indicating the presence of substantial vasodilator reserve. Stimulation of metabolism in the ischemic area by norepinephrine infusion increased flow by 54 .+-. 17%. Indomethacin treatment after 180 min of ischemia caused left anterior descending coronary artery flow to decrease by 22 .+-. 8%. .alpha.-Receptor blockade (phenoxybenzamine) in the left anterior descending coronary artery bed prior to ischemia prevented the flow decrease between 30-180 min. Phentolamine administration after 180 min also resulted in increased left anterior descending coronary artery flow. The addition of propranolol to phenoxybenzamine-treated hearts reversed the vasodilatory influence of phenoxybenzamine, resulting in a flow decrease within the ischemic region similar to that seen without any pharmacological intervention. Apparently, during 3 h of relative ischemia in this preparation, blood vessels in the ischemic area are not maximally dilated, and undergo a progressive vasoconstriction via an unknown mechanism. Phenoxybenzamine prevents the progressive vasoconstriction, apparently by increasing norepinephrine release.