Progressive Coronary Vasoconstriction during Relative Ischemia in Canine Myocardium

Under certain conditions, a progressive increase in vascular resistance occurs within ischemic myocardium during the first 3 hours after coronary artery stenosis. We tested the hypothesis that the increased resistance is due to local release of a vasoconstrictor substance in the ischemic region. 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 μm microspheres after 30 and 180 minutes 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 minutes 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 minutes of ischemia, however, caused left anterior descending coronary artery flow to decrease by 22 ± 8%. a-Receptor blockade (phenoxybenzamine) in the left anterior descending coronary artery bed prior to ischemia prevented the flow decrease between 30 and 180 minutes. Phentolamine administration after 180 minutes also resulted in increased left anterior descending coronary artery flow. However, 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. We conclude that during 3 hours of relative ischemia in this preparation, blood vessels in the ischemic area (1) are not maximally dilated, and (2) undergo a progressive vasoconstriction via an unknown mechanism. Phenoxybenzamine prevents the progressive vasoconstriction, apparently by increasing norepinephrine release.