Plasma-mediated stimulation of neutrophil superoxide anion production during coronary artery bypass grafting: Role of endothelin-1

Background: Activation of polymorphonuclear neutrophils (PMN) and subsequen t release of free oxygen radicals, ;including the superoxide anion (0(2)(-) ) has been shown to result in postischaemic myocardial dysfunction during c oronary artery bypass grafting (CABG). Several neutrophil-oriented stimuli are known to be released from myocardium during ischaemia and reperfusion. Release of endothelin-1 has been documented during CABG. The aim of the cur rent study was to evaluate plasma-mediated neutrophil stimulation and to ve rify whether endothelin-1, known to be a stimulus for PMN, is involved in p lasma-mediated stimulation of PMN during coronary artery bypass grafting. M ethods: Plasma samples from peripheral artery, peripheral vein, and coronar y sinus were obtained from 21 patients undergoing CABG before aortic clampi ng (global ischaemia), immediately after beginning reperfusion, and 30 min after reperfusion as well as from healthy controls. Plasma was incubated wi th PMN isolated from healthy donors preincubated in the presence of saline or specific endothelin-1 receptor antagonist (ET-A). PMN O-2(-) production was measured spectrophotometrically. Results: Plasma samples taken from the coronary sinus at the beginning of reperfusion were capable of higher stim ulation of neutrophil superoxide anion production (24.2+/-2.0 nmo1/5x10(6)P MN/30 min) than plasma obtained before reperfusion (15.6+/-1.5; p < 0.05) o r plasma taken from peripheral artery (17.1+/-1.7; p < 0.05). Preincubation of PMN with endothelin-1 receptor antagonist decreased superoxide anion pr oduction by cells exposed to plasma taken from coronary sinus at the beginn ing of reperfusion (17.6+/-2.0, p < 0.05). Conclusions: Transcardiac releas e of soluble stimuli for PMN occurs as a result of myocardial ischaemia dur ing CABG. Endothelin-1 may be involved in the plasma-mediated stimulation o f neutrophil superoxide anion production.