Background-Increased plasminogen activator inhibitor-1 (PAI-1) concentrations after coronary artery bypass grafting (CABG) are associated with increased risk of vein graft occlusion. Because angiotensin II stimulates PAI-1 expression, we tested the hypothesis that preoperative angiotensin-converting enzyme (ACE) inhibition decreases PAI-1 expression after CABG. Methods and Results-We measured the effects of cardiopulmonary bypass (CPB) on PAI-1 antigen and tissue-type plasminogen activator (tPA) antigen and activity in 31 patients taking an ACE inhibitor (ACEI) who were randomized to continue ACEI until the morning of surgery (ACEI group, nϭ19) or to discontinue it 48 hours before surgery (No-ACEI group, nϭ12). Arterial blood samples were taken at baseline before CPB, twice during CPB, after separation from CPB, and on postoperative day 1 (POD1). CPB caused an early decrease in PAI-1 antigen, followed by an increase in PAI-1 antigen on POD1 (PϽ0.001 for effect of time). ACE inhibition attenuated the increase in PAI-1 antigen such that both PAI-1 antigen on POD1 (Pϭ0.013) and the change in PAI-1 antigen from baseline to POD1 (Pϭ0.009) were higher in the No-ACEI group (from 17.0Ϯ5.0 to 48.7Ϯ8.8 ng/mL) versus the ACEI group (from 19.9Ϯ3.4 to 33.1Ϯ6.2 ng/mL). There was no significant difference between the 2 groups in intraoperative tPA activity (Pϭ0.259); however, the increase in tPA activity was significantly greater in the ACEI group than in the No-ACEI group (Pϭ0.030). Conclusions-Preoperative

Preoperative ACE inhibitors and smoking potentiate the kinin response to CPB and may contribute to the hemodynamic and fibrinolytic response observed during CPB.

Increased bradykinin contributes to protamine-related hypotension through its B(2) receptor in ACE inhibitor-treated patients.