Aprotinin combined with nitric oxide and prostaglandin E1 protects the canine kidney from cardiopulmonary bypass-induced injury

Objective: Aprotinin is frequently used to reduce blood loss during cardiac surgery; however, it also causes renal injury. Since aprotinin reduces nitric oxide (NO) and prostaglandin I-2 (PGI(2)), and both cause vasodilation and inhibit activation of neutrophils and platelets, their reduction may be responsible for the injury. This study was to determine whether the combination of aprotinin with NO and prostaglandin E-1 (PGE(1)), an analogue of PGI(2)) can attenuate renal injury associated with aprotinin during cardiopulmonary bypass (CPB). Methods: Thirty mongrel dogs were equally divided into five groups, with each group receiving CPB and aprotinin, NO, PGE(1), a combination of the three or no treatment (control). Serum creatinine and creatinine clearance were determined. To elucidate the mechanism, neutrophil, platelet and thrombin activations were also assessed. Results: After CPB, serum creatinine increased and creatinine clearance decreased in all dogs. These changes were similar among the NO, PGE(1), aprotinin and control groups, but were significantly smaller in the combination group. Similarly, myeloperoxidase activities in tissues, CD11b expression, plasma elastase, prothrombin fragment (PTF) 1 + 2 and platelet activation factor were lower, whereas neutrophil and platelet counts were higher in the combination group than in the other groups (P < 0.05). Conclusions: Aprotinin combined with NO and PGE(1) produced synergistic protective effects and improved renal function, due partly to inhibition of platelet and neutrophil activation and suppression of thrombin formation. (C) 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.