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

BACKGROUND
Activation of polymorphonuclear neutrophils (PMN) and subsequent release of free oxygen radicals, including the superoxide anion (O2-) has been shown to result in postischaemic myocardial dysfunction during coronary 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 current study was to evaluate plasma-mediated neutrophil stimulation and to verify whether endothelin-1, known to be a stimulus for PMN, is involved in plasma-mediated stimulation of PMN during coronary artery bypass grafting.


METHODS
Plasma samples from peripheral artery, peripheral vein, and coronary sinus were obtained from 21 patients undergoing CABG before aortic clamping (global ischaemia), immediately after beginning reperfusion, and 30 min after reperfusion as well as from healthy controls. Plasma was incubated with PMN isolated from healthy donors preincubated in the presence of saline or specific endothelin-1 receptor antagonist (ET-A). PMN O2- production was measured spectrophotometrically.


RESULTS
Plasma samples taken from the coronary sinus at the beginning of reperfusion were capable of higher stimulation of neutrophil superoxide anion production (24.2 +/- 2.0 nmol/5 x 10(6)PMN/30 min) than plasma obtained before reperfusion (15.6 +/- 1.5; p < 0.05) or plasma taken from peripheral artery (17.1 +/- 1.7; p < 0.05). Preincubation of PMN with endothelin-1 receptor antagonist decreased superoxide anion production by cells exposed to plasma taken from coronary sinus at the beginning of reperfusion (17.6 +/- 2.0, p < 0.05).


CONCLUSIONS
Transcardiac release of soluble stimuli for PMN occurs as a result of myocardial ischaemia during CABG. Endothelin-1 may be involved in the plasma-mediated stimulation of neutrophil superoxide anion production.