This study tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitors potentiate activation of the kallikrein-kinin system during cardiopulmonary bypass (CPB). The effects of CPB on concentrations of bradykinin and its metabolite bradykinin 1-5 (BK1-5) were determined in 31 patients taking an ACE inhibitor who were randomized to continue ACE inhibitors until coronary artery bypass surgery (ACE inhibitor group, N = 19) or to discontinue them 48 hours before surgery (no ACE inhibitor group, N = 12). Arterial and venous blood was sampled before CPB, at 30 minutes of CPB, at 60 minutes of CPB, after separation from CPB, and on postoperative day 1. Arterial bradykinin (P < .001 [from 22.4 ± 24.1 fmol/mL to 86.2 ± 98.7 fmol/mL in the no ACE inhibitor group]) and arterial (P < .001) and venous (P =. 016) BK1-5 concentrations increased significantly during CPB. Arterial bradykinin concentrations were significantly higher (P =. 017), whereas BK1-5 concentrations (P =. 024) and the molar ratio of BK1-5/bradykinin (P =. 008) were significantly lower in the ACE inhibitor group compared with the no ACE inhibitor group. In addition, arterial bradykinin concentrations were significantly increased in smokers compared with nonsmokers (P =. 015), when we controlled for the ACE inhibitor group. There was no effect of smoking on ACE activity (P =. 597 overall). There was a significant inverse correlation between arterial bradykinin and mean arterial pressure (r2 = 0.2137, P =. 010) and a significant correlation between arterial bradykinin and tissue-type plasminogen activator antigen concentrations (r2 = 0.174, P =. 022) during CPB. Tissue-type plasminogen activator antigen was significantly higher in the ACE inhibitor group than in the no ACE inhibitor group (18.0 ± 7.8 ng/mL versus 12.4 ± 4.5 ng/mL, P =. 016) but not in smokers compared with nonsmokers (P =. 451). Preoperative ACE inhibitors and smoking potentiate the kinin response to CPB and may contribute to the hemodynamic and fibrinolytic response observed during CPB.
ASJC Scopus subject areas
- Pharmacology (medical)