Conjugated Estrogens Acutely Abolish Abnormal Cold-Induced Coronary Vasoconstriction in Male Cardiac Allografts

Abstract

Background —Transplant-associated coronary arteriopathy is manifested in its early stages by paradoxical coronary artery constriction in response to endothelium-dependent vasodilator stimuli such as the cold pressor test (CPT) and is a major cause of death or retransplantation. Estrogen has vasoactive properties that abolish coronary artery endothelial dysfunction in native hearts. We hypothesized that estrogen attenuates inappropriate coronary artery constriction in cardiac allografts. Methods and Results —Coronary artery diameter and systemic hemodynamic responses to a 90-second CPT were measured before and 15 minutes after double-blind, randomized administration of intravenous conjugated estrogens (1.25 mg) or placebo in men with male cardiac allografts. Before estrogen, 9 men exhibited an abnormal 15.1±3.0% CPT-induced decrease in coronary artery diameter. However, repeat CPT did not induce significant coronary artery constriction when performed 15 minutes after estrogen. CPT responses before and after estrogen were significantly different ( P =.02). Placebo did not influence coronary artery responses to CPT in 6 men. Systemic hemodynamic responses to CPT were not influenced by estrogen or placebo. Estrogen was the only significant determinant of changes in coronary artery responses to CPT. Conclusions —Conjugated estrogens acutely abolish abnormal CPT-induced coronary artery constriction in male cardiac allografts. This favorable vasomotor effect suggests that estrogen may prevent inappropriate coronary artery constriction in men with cardiac transplants.