Thorac Cardiovasc Surg 2002; 50(3): 150-154
DOI: 10.1055/s-2002-32409
Original Cardiovascular
Original Paper
© Georg Thieme Verlag Stuttgart · New York

Influence of ACE Inhibition on Myocardial Damage,
the Kallikrein-Kinin System and Hemostasis
during Cardiopulmonary Bypass Surgery

T.  Walter1 , U.  Helber1 , D.  Bail2 , W.  Heller1 , H.  M.  Hoffmeister1
  • 1Department of Internal Medicine III, University of Tübingen, Germany
  • 2Department of Thoracic, Cardiac and Vascular Surgery, University of Tübingen, Germany
Further Information

Publication History

Publication Date:
21 June 2002 (online)

Abstract

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.

References

  • 1 Martorana P A, Linz W, Scholkens B A. Does bradykinin play a role in the cardiac antiischemic effect of the ACE-inhibitors?.  Basic Res Cardiol. 1991;  86 293-296
  • 2 Katus H A, Schoeppenthau M, Tanzeem A. et al . Non-invasive assessment of perioperative myocardial cell damage by circulating cardiac troponin T.  Br Heart J. 1991;  65 259-264
  • 3 Sadony V, Korber M, Albes G. et al . Cardiac troponin I plasma levels for diagnosis and quantitation of perioperative myocardial damage in patients undergoing coronary artery bypass surgery.  Eur J Cardiothorac Surg. 1998;  13 57-65
  • 4 Wendel H P, Heller W, Michel J. et al . Lower cardiac troponin T levels in patients undergoing cardiopulmonary bypass and receiving high-dose aprotinin therapy indicate reduction of perioperative myocardial damage.  J Thorac Cardiovasc Surg. 1995;  109 1164-1172
  • 5 Mannucci L, Gerometta P S, Mussoni L. et al . One month follow-up of haemostatic variables in patients undergoing aortocoronary bypass surgery. Effect of aprotinin.  Thromb Haemost. 1995;  73 356-361
  • 6 Porter J M, Silver D. Alterations in fibrinolysis and coagulation associated with cardiopulmonary bypass.  J Thorac Cardiovasc Surg. 1968;  56 869-878
  • 7 Napoleone E, Di-Santo A, Camera M, Tremoli E, Lorenzet R. Angiotensin-converting enzyme inhibitors downregulate tissue factor synthesis in monocytes.  Circ Res. 2000;  86 139-143
  • 8 Hernandez-Presa M A, Bustos C, Ortego M, Tunon J, Ortega L, Egido J. ACE inhibitor quinapril reduces the arterial expression of NF-kappaB-dependent promflammatory factors but not of collagen I in a rabbit model of atherosclerosis.  Am J Pathol. 1998;  153 1825-1837
  • 9 Uchino T, Belboul A, Roberts D, Jagenburg R. Measurement of myosin light chain I and troponin T as markers of myocardial damage after cardiac surgery.  J Cardiovasc Surg Torino. 1994;  35 201-206
  • 10 Bonnefoy E, Filley S, Kirkorian G. et al . Troponin I, troponin T, or creatine kinase-MB to detect perioperative myocardial damage after coronary artery bypass surgery.  Chest. 1998;  114 482-486
  • 11 Califf R M, Abdelmeguid A E, Kuntz R E. et al . Myonecrosis after revascularization procedures.  J Am Coll Cardiol. 1998;  31 241-251
  • 12 Hossein N ia, Kallis P, Brown P A. et al . Creatine kinase MB isoforms: sensitive markers of ischemic myocardial damage.  Clin Chem. 1994;  40 1265-1271
  • 13 van Lente F, McHugh A M, Galen R S. Changes in serum CK-MB mass after coronary artery bypass surgery.  Clin Biochem. 1987;  20 333-337
  • 14 Linz W, Scholkens B A. Influence of local converting enzyme inhibition on angiotensin and bradykinin effects in ischemic rat hearts.  J Cardiovasc Pharmacol. 1987;  10 (Suppl 7) S75-82
  • 15 Boldt J, Rothe G, Schindler E, Doll C, Gorlach G, Hempelmann G. Can clonidine, enoximone, and enalaprilat help to protect the myocardium against ischaemia in cardiac surgery?.  Heart. 1996;  76 207-213
  • 16 Davis R, Whittington R. Aprotinin. A review of its pharmacology and therapeutic efficacy in reducing blood loss associated with cardiac surgery.  Drugs. 1995;  49 954-983
  • 17 Kongsgaard U E, Smith E richsen, Geiran O, Bjornskau L. Changes in the coagulation and fibrinolytic systems during and after cardiopulmonary bypass surgery.  Thorac Cardiovasc Surg. 1989;  37 158-162
  • 18 Gomazkov O A. The kallikrein-kinin system in myocardial ischemia and myocardial infarct. Experimental studies.  Med Welt. 1974;  25 804-807
  • 19 Mori F, Nakahara Y, Kurata S, Furukawa S, Esato K, Mohri H. Late changes in hemostatic parameters following open-heart surgery.  J Cardiovasc Surg Torino. 1982;  23 458-462
  • 20 Menges T, Wagner R M, Welters I, Ruwoldt R, Boldt J, Hempelmann G. The role of the protein C-thrombomodulin system and fibrinolysis during cardiovascular surgery: influence of acute preoperative plasmapheresis.  J Cardiothorac Vase Anesth. 1996;  10 482-489
  • 21 Hoffmeister H M, Jur M, Wendel H P, Heller W, Seipel L. Alterations of coagulation and fibrinolytic and kallikrein-kinin systems in the acute and postacute phases in patients with unstable angina pectoris.  Circulation. 1995;  91 2520-2527
  • 22 Hoffmeister H M, Ruf M, Wendel H P, Heller W. Alterations of the kallikrein system in patients with acute myocardial syndromes in comparison with patients with stable angina pectoris.  Pharm Pharmacol. 1993;  3 72-74

Dr. med. Thomas Walter

Medizinische Universitatsklinik, Abteilung Innere Medizin III


Otfried-Muller-Straße 10

72076 Tübingen

Germany

Phone: +49/7071/29-82714

Fax: +49/7071/29-2088

Email: Thomas.Walter@med.uni-tuebingen.de