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

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.

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.

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.

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.