Aprotinin improves cerebral protection: Evidence from a survival porcine model

Objective: Aprotinin is a serine protease inhibitor used during cardiac surgery to reduce blood loss and preserve platelet function. It has also been shown to reduce leukocyte activation during and after cardiopulmonary bypass. The goal of the study was to test the hypothesis that aprotinin could reduce cerebral injury after low-flow cardiopulmonary bypass and deep hypothermic circulatory arrest. Methods: Sixteen piglets (mean weight, 13.6 ± 1.3 kg) were randomly assigned to receive aprotinin or placebo (8 animals per group) before a 120-minute period of deep hypothermic circulatory arrest (15°C) or 25 mL · kg^-1 · min^-1 low-flow cardiopulmonary bypass (25°C or 34°C). Piglets had a cranial window placed over the parietal cerebral cortex for direct examination of the microcirculation by means of intravital microscopy. Rhodamine-stained leukocytes were observed in postcapillary venules, with analysis for adhesion and rolling. Plasma was labeled with fluorescein isothiocyanate-dextran for assessment of functional capillary density. Neurologic and histologic scores were used as the primary outcome measures. Results: During rewarming, the mean number of both rolling and adherent leukocytes was significantly lower after aprotinin administration (P < .05). At 5 and 15 minutes of rewarming, functional capillary density recovered faster with aprotinin treatment (P < .05). Functional outcome (neurologic deficit score) on postoperative day 1 was significantly improved in aprotinin-treated piglets (P < .05). Conclusions: Aprotinin reduces inflammation and improves neurologic outcome after a prolonged period of deep hypothermic circulatory arrest or low-flow cardiopulmonary bypass.