Objective: We hypothesized that antithrombotic plasma-activated protein G p
lays a defensive antithrombotic role during coronary ischemia and postische
mic reperfusion, Methods and results: We evaluated protein C activation dur
ing cardiopulmonary bypass and coronary reperfusion in 20 patients undergoi
ng 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 nor
mal mean. In contrast, the levels of activated protein C in plasma increase
d from 122% +/- 8% to 159% +/- 21%, and the activated protein C/protein C r
atio increased from 1.04 +/- 0.08 to 2.29 +/- 0.31 (P = .006, 2-tailed Wilc
oxon signed rank test). patients were stratified on the basis of the increa
se 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 prote
in C/protein C ratio, Within 24 hours, the patients with low increases in a
ctivated 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 sys
temic vascular resistance, than patients (n = 11) with high increases in ac
tivated protein C (ratio > 1.5). The rapid increase in activated protein C
during the first 10 minutes after aortic unclamping indicated protein C act
ivation in the reperfused vascular beds. Conclusions: The antithrombotic pr
otein C pathway was significantly activated during cardiopulmonary bypass m
ainly during the minutes after aortic unclamping in the ischemic vascular b
eds. Suboptimal protein C activation during ischemia may impair the postisc
hemic recovery of human heart and circulation.