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Eur J Cardiothorac Surg 2005;28:801-804
© 2005 Elsevier Science NL

Effects of aprotinin on endothelium-dependent relaxation of large coronary arteries

Institute of Experimental Medicine, University of Cologne, Robert-Koch-Str. 10, Cologne 50931, Germany

Received 10 March 2005; received in revised form 26 August 2005; accepted 13 September 2005.

^_* Corresponding author. Tel.: +49 221 478 4129; fax: +49 221 478 6264. (Email: JH.Fischer{at}uni-koeln.de).

Objective: Aprotinin is widely used in heart surgery for reduction of intraoperative blood loss. But recent reports presenting results from rat aorta experiments claimed that aprotinin selectively impairs endothelium-dependent relaxation (EDR) as well as basal NO availability in concentrations similar to doses routinely used in cardiovascular surgery. An impairment of coronary EDR by aprotinin would be a great danger for any cardiothoracic intervention. We therefore tested the influence of aprotinin in the coronary arteries of a non-rodent species. Methods: Fresh coronary arteries of pigs were obtained from the local slaughterhouse and transported to our laboratory in cold oxygenated Krebs–Henseleit solution. Five-millimeter long rings were consecutively tested with or without aprotinin in concentrations of 500 KIU/ml (n = 7) or 1000 KIU/ml (n = 6) in oxygenated normothermic Krebs–Henseleit solution. PGF₂ (10 µmol/l) was used for inducing contraction and substance P (10 nmol/l) for inducing EDR, which was calculated in percentage of the precontraction. Indomethacin (10 µmol/l) was added in all measurements to eliminate the influence of prostaglandins. In additional similar experiments (n = 5), the influence of 1000 KIU/ml aprotinin on the EDR caused by the endothelium-derived hyperpolarizing factor (EDHF) was tested using L-NNA (300 µmol/l) to block all NO formation. Results: The EDR of pig coronaries (82 ± 5% or 80 ± 5% of the precontraction in the control tests before and after aprotinin exposure) was not significantly changed by 500 KIU/ml aprotinin (78 ± 7%). A small, but significant reduction of less than 1/10 of the EDR was induced by 1000 KIU/ml aprotinin (74 ± 5%). After accounting for L-NNA for NO blockage, no aprotinin-related difference remained (59 ± 6% vs 60 ± 6% in controls). Conclusion: For clinically relevant concentrations of aprotinin up to 500 KIU/ml, no significant reduction of the EDR can be found in epicardial coronary arteries of the pig. For higher doses of 1000 KIU/ml, a reduction in NO production seems to be the cause of the small but significant reduction of the EDR by aprotinin. Therefore, danger for impairment of coronary EDR by aprotinin at clinical dosage levels, as suggested by studies on rat aortas, seems to be absent in coronary arteries of a large mammalian model.

Key Words: Aprotinin • Endothelium-dependent relaxation (EDR) • Coronary artery • EDHF