Cardiopulmonary bypass and activation of antithrombotic plasma protein C

Objective: We hypothesized that antithrombotic plasma-activated protein C plays a defensive antithrombotic role during coronary ischemia and postischemic reperfusion. Methods and results: We evaluated protein C activation during cardiopulmonary bypass and coronary reperfusion in 20 patients undergoing coronary bypass surgery. During cardiopulmonary bypass and during the 10 minutes after aortic unclamping, the plasma levels of protein C (mean ± standard error of the mean) decreased from 123% ± 7% to 74% ± 5% of normal mean. In contrast, the levels of activated protein C in plasma increased from 122% ± 8% to 159% ± 21%, and the activated protein C/protein C ratio increased from 1.04 ± 0.08 to 2.29 ± 0.31 (P = .006, 2- tailed Wilcoxon signed rank test). Patients were stratified on the basis of the increase in activated protein C in the coronary sinus plasma at 10 minutes after reperfusion by means of the arbitrary value of 1.5 for the activated protein C/protein C ratio. Within 24 hours, the patients with low increases in activated protein C (ratio < 1.5, n = 8) had a significantly (P < .05) lower cardiac output and mean pulmonary artery pressure, as well as a higher systemic vascular resistance, than patients (n = 11) with high increases in activated protein C (ratio > 1.5). The rapid increase in activated protein C during the first 10 minutes after aortic unclamping indicated protein C activation in the reperfused vascular beds. Conclusions: the antithrombotic protein C pathway was significantly activated during cardiopulmonary bypass mainly during the minutes after aortic unclamping in the ischemic vascular beds. Suboptimal protein C activation during ischemia may impair the postischemic recovery of human heart and circulation.