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Eur J Cardiothorac Surg 2007;32:340-345. doi:10.1016/j.ejcts.2007.02.039
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

Effect of recombinant aprotinin on postoperative blood loss and coronary vascular function in a canine model of cardiopulmonary bypass

^a Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
^b Department of Cardiovascular Surgery, Semmelweis University, Budapest, Hungary
^c Bayer HealthCare, Wuppertal, Germany
^d Department of Cardiovascular Surgery, University of Freiburg, Germany

Received 14 November 2006; received in revised form 15 February 2007; accepted 28 February 2007.

^_* Corresponding author. Address: Laboratory of Cardiac Surgery, Department of Cardiac Surgery, University of Heidelberg, INF 326. OG 2, 69120 Heidelberg, Germany. Tel.: +49 6221 566246; fax: +49 6221 564571. (Email: dzsi{at}hotmail.com).

Objective: Aprotinin is a widely used serine protease inhibitor during cardiopulmonary bypass to reduce blood loss and preserve platelet function. However, the bovine-derived aprotinin can induce hypersensitivity reaction with fatal complications. Furthermore, vascular effects of aprotinin are not completely elucidated. The current study is designed to investigate the effects of recently developed recombinant aprotinin on blood loss and coronary vascular function in a clinically relevant canine model of cardiopulmonary bypass without aortic cross-clamping and cardioplegia. Methods: Twenty-four dogs underwent cardiopulmonary bypass without aortic cross-clamping and cardioplegia. Dogs were divided into three groups in a blinded fashion: control animals (n = 8) received placebo, aprotinin treatment groups received bovine (n = 8) or recombinant aprotinin (n = 8) according to the Hammersmith method. The doses of bovine and recombinant aprotinin were the same. Coagulation parameters and blood loss were measured regularly at different time points. Endothelium-dependent and -independent vasorelaxation were investigated in isolated left anterior descendent coronary arterial rings by using acetylcholine and bradykinin or sodium nitroprusside and adenosine, respectively. Results: Postoperative blood loss was significantly reduced in the aprotinin-treated groups in comparison to control and there was no significant difference between the two aprotinin-treated groups. Endothelium-dependent relaxation of coronary arteries to acetylcholine and bradykinin was unaffected in the aprotinin treatment groups. Both types of aprotinin significantly increased vasorelaxation to adenosine when compared with controls, but did not affect that to sodium nitroprusside. Conclusions: The effectiveness of recombinant aprotinin on blood loss was equivalent to bovine-derived aprotinin. Neither types of aprotinin impaired endothelium-dependent relaxation in a canine model of cardiopulmonary bypass.

Key Words: Aprotinin • Cardiopulmonary bypass • Blood loss • Coronary endothelial function • Vasorelaxation