Vasodilator actions of interleukin-1 in the canine coronary circulation

The effects of intracoronary ultrapure human Interleukin-1 on the regional distribution of coronary blood flow (radioactive microspheres), contractile function (subendocardial ultrasonic length gauges) and systemic hemodynamics were studied in open-chest, anesthetized dogs (n = 7). Bolus doses of Interleukin-1 (10, 20, and 30 u) administered directly into the left anterior descending coronary artery increased coronary blood flow from 43 to 71, 80 and 87 ml/min, respectively. The increase in blood flow produced by Interleukin-1 was distributed uniformly to the subendocardium, midmyocardium, and subepicardium of the left ventricular free wall without effect on regional function or systemic hemodynamics. Indomethacin (1 mg/kg i.v.) attenuated the increase in blood flow, especially to the subepicardium. Due to the selective diminution of the Interleukin-1-mediated increase in subepicardial blood flow by indomethacin, the subendocardial to subepicardial perfusion ratio was increased by Interleukin-1 in the presence of indomethacin. The present results demonstrate that Interleukin-1 has direct coronary vasodilator actions, a portion of which is mediated by a product of cyclooxygenase metabolism.