Altered effects of vasopressin on the coronary circulation after ischemia

Abstract

Ischemia and reperfusion alter the reactivity of large coronary arteries, but the effect of ischemia and reperfusion on the coronary microcirculation has been less well defined. Elevated circulating levels of vasopressin are associated with cardiopulmonary bypass and numerous other clinical states in which vascular ischemia and reperfusion may occur. We examined the effects of ischemia with and without reperfusion on the responses to vasopressin of both large coronary arteries and coronary arterial microvessels. Studies were performed on vessels from control dogs (n = 8), dogs undergoing 1 hour of ischemia only (n = 8), and dogs undergoing 1 hour of ischemia followed with 1 hour of reperfusion (n = 9). Rings of proximal obtuse marginal coronary arteries distal to the site of circumflex coronary artery occlusion were studied in isolated organ chambers. Coronary microvessels (110 to 220 microns in diameter) were studied in a pressurized (20 mm Hg), no-flow state with a microvessel imaging apparatus and electronic dimension analyzer. Microvessels were preconstricted with the thromboxane A2 analog U46619. Responses of large vessel rings were studied in the nonpreconstricted state and after preconstriction with prostaglandin F2 alpha. Large vessel response to vasopressin was minimal and not altered by ischemia with or without reperfusion. In contrast, ischemia markedly affected the coronary microvascular response to vasopressin (10 to 1000 microU/ml). Control coronary microvessels constricted minimally to vasopressin (4% +/- 2% of the baseline diameter), while microvessels after either ischemia alone or ischemia followed by reperfusion constricted 22% +/- 5% and 21% +/- 3%, respectively (p less than 0.05 versus control for both). Hemoglobin, which inactivates the endothelium-derived relaxing factor, augmented microvascular constrictions to vasopressin in all groups to a similar extent. Relaxations to the endothelium-independent agent nitroglycerin were not altered by ischemia. Constrictions of the coronary microcirculation to vasopressin in conditions such as cardiopulmonary bypass or myocardial ischemia, in which circulating levels of vasopressin are increased, may predispose to persistent myocardial ischemia in the perioperative setting.