Reduced release of vasoconstrictors from the porcine heart after repeated periods of ischemia

Objective To examine if the decline in post-ischemic hyperemic flow after repeated brief periods of myocardial ischemia is accompanied by augmented cardiac release of the vasoconstrictors endothelin-1 (ET-1) and norepinephrine (NE). Design Mid-LAD (left anterior descending coronary artery) was occluded for 10 min with 30 min intervals a total of four times in six anesthetized pigs. Blood from the anterior interventricular coronary vein was drained through a shunt to the right atrium to facilitate blood sampling. Plasma concentrations of ET-1 and NE were repeatedly measured in arterial and coronary venous blood to estimate cardiac vasoconstrictor release. Results Plasma concentrations of ET-1 and NE remained unaltered, but cardiac release of both vasoconstrictors rose briefly during reperfusion due to the hyperemia. However, release declined progressively after repeated periods of ischemia and reperfusion and amounted to 53% (NE) and 17% (ET-1) of initial release after the fourth period of ischemia. Conclusion The decline in post-ischemic hyperemia after repeated brief periods of myocardial ischemia is not accompanied by a progressive accentuation of cardiac ET-1 and NE release.