Modulation of endothelin-1 release by a transmissible factor from ischemic myocardium.

The aim of this study was to detect the possible release from the ischemic rabbit myocardium of a factor capable of modulating the release of endothelin-1 (ET-1) from the peripheral vasculature. Isolated rabbit hearts were perfused on a Langendorff apparatus so that part of the coronary effluent was pumped directly into the arterial supply of isolated ears. Mean ET-1 outflow from ears perfused with fresh Krebs was 4.33 +/- 0.72 pg/min; from ears perfused with coronary effluent it was 84.3% less. This still represented net ET-1 production in the ear (venous/arterial ET-1 concentration ratio (V/A) = 3.9 +/- 1.2). Myocardial ischemia (30 min) caused a large reduction in ET-1 outflow from the ears and changed net production to net loss (V/A = 0.32 +/- 0.17). Within 2 min of reperfusion the V/A had risen to 6.3 +/- 2.2 and the ET-1 outflow from the ears rose 16-fold. Neither 30-min coronary occlusion nor 2-min reperfusion altered ET-1 concentrations in the coronary effluents. After 60-min reperfusion, ET-1 concentration in coronary effluent rose by 230%. During myocardial ischemia and reperfusion there was no change in pO2, pCO2 or pH in the perfusate supplying the ears. Therefore the changes in ET-1 handling by the ear vasculature must have been induced by a transmissible factor released from the heart.