Angiotensin-converting enzyme inhibition and smoking potentiate the kinin response to cardiopulmonary bypass.
BACKGROUND
This study tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitors potentiate activation of the kallikrein-kinin system during cardiopulmonary bypass (CPB).


METHODS
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.


RESULTS
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 ( r 2 = 0.2137, P = .010) and a significant correlation between arterial bradykinin and tissue-type plasminogen activator antigen concentrations ( r 2 = 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).


CONCLUSIONS
Preoperative ACE inhibitors and smoking potentiate the kinin response to CPB and may contribute to the hemodynamic and fibrinolytic response observed during CPB.
Pretorius
Mias
M
Veterans Affairs Medical Center and Department of Anesthesiology, and Division of Cardiovascular Medicine. mias.pretorius@vanderbilt.edu
McFarlane
Julie A
JA
Vaughan
Douglas E
DE
Brown
Nancy J
NJ
Murphey
Laine J
LJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001920:Bradykinin / Q000097:blood / Q000187:drug effects*; D001026:Coronary Artery Bypass; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects*; D012907:Smoking / Q000009:adverse effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; C079000:bradykinin (1-5); D001920:Bradykinin