Influence of ACE inhibition on myocardial damage, the Kallikrein-Kinin system and hemostasis during cardiopulmonary bypass surgery.
BACKGROUND
ACE inhibitors may have a cardioprotective effect by enhancing bradykinin levels during cardiopulmonary bypass (CPB). However, ACE inhibition could lead to unwelcome effects on the kallikrein contact phase during CPB (since reduction of kallikrein activity by aprotinin has been shown to be beneficial) and may alter the hemostasis. We examined the effects of ACE inhibitors on intraoperative myocardial damage, kallikrein contact phase and hemostasis in patients undergoing CPB.


METHODS
47 patients randomly received either 20 mg/d enalapril or placebo. Creatine kinase (CK and CK-MB), lactate dehydrogenase (LDH), troponin T (TnT), thrombin-antithrombin III complex (TAT), fibrinogen and kallikrein-like activity were measured before surgery, during and immediately after CPB, at the end of surgery and 1, 3 and 5 days after surgery.


RESULTS
No significant differences between enalapril- and placebo- treated patients concerning CK (318 +/- 38.6 U/l vs. 316 +/- 16.8 U/l), CK-MB, LDH, TnT (1.81 +/- 0.45 ng/ml vs. 1.52 +/- 0.34 ng/ml), TAT, fibrinogen and kallikrein-like-activity could be found during study period.


CONCLUSIONS
Reduction of ischemic injury during CPB is not achieved with ACE inhibitors. However, treatment of patients with ACE inhibitors before and during CPB is fully feasible without side effects affecting the kallikrein contact phase or significant influence on hemostasis.
Walter
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Department of Internal Medicine III, University of Tübingen, Germany. Thomas.Walter@med.uni-tuebingen.de
Helber
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Bail
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D
Heller
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W
Hoffmeister
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HM
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000601:surgery; D004311:Double-Blind Method; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006321:Heart / Q000187:drug effects*; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007431:Intraoperative Complications / Q000517:prevention & control*; D016234:Kallikrein-Kinin System / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D005340:Fibrinogen