Endothelin-1 is involved in plasma mediated stimulation of neutrophil adherence during coronary artery bypass grafting

Objective: Myocardial ischaemia followed by reperfusion during coronary artery bypass grafting (CABG) is known to result in the activation of polymorphonuclear neutrophils (PMN). The activation of PMN during ischaemia/reperfusion may be a result of their direct contact with activated endothelial cells and/or an effect of stimuli released from ischaemic myocardium. Increased expression of adhesion molecules on the PMN surface, after activation, leads to coronary capillary plugging with a subsequent decrease in blood flow. The purpose of the study was to evaluate plasma-mediated stimulation of PMN adhesion during CABG and to verify if endothelin-1 (ET-1), known to be a potent stimulus for PMN, is involved in stimulation of neutrophils adhesion mediated by integrins. Methods: Coronary sinus, peripheral artery and peripheral venous plasma samples were taken from 11 patients undergoing coronary surgery before aortal cross-clamping, at the beginning of reperfusion and 30 min thereafter. PMN isolated from five healthy volunteers were incubated with the plasma (20 samples per patient) in the presence of saline or a specific ET-1 receptor blocker, and PMN adherence to a microtiter plate covered with a monoclonal antibody against CD 18 antigen (beta-subunit of the integrin family of adhesion molecules) was evaluated. Results: We have observed a significant increase in adhesion of PMN incubated in the presence of saline with the plasma taken from coronary sinus at the beginning of reperfusion (7.79 +/- 1.64% of adhering cells) as compared with plasma obtained before aortal cross-clamping from the same place (6.78 +/- 1.3%, P = 0.04) and from peripheral artery at the beginning of reperfusion (6.64 +/- 1.1%, P = 0.04, means +/- SEM). ET-1 receptor blocker, significantly decreased stimulation of PMN adhesion by coronary sinus plasma obtained at the beginning of reperfusion (6.7 +/- 1.51%, P = 0.02). Plasma levels of ET-1 (ELISA) in the samples taken from coronary sinus at the beginning of reperfusion, were higher than in samples obtained before myocardial ischaemia or 30 min after reperfusion. Conclusions: We conclude, that soluble stimuli capable of stimulation of PMN adhesion are released following myocardial ischaemia during CABG and ET-1 may be involved in PMN stimulation. (C) 1999 Elsevier Science B.V. All rights reserved.