Aprotinin protects the cerebral microcirculation during cardiopulmonary bypass

Background and objective: We have previously reported that administration of aprotinin at a single dose protects the cerebral microcirculation. The current study was designed to identify the optimal dose for protecting the cerebral microcirculation with assessment of neurological and behavioral recovery as well as renal function after circulatory arrest and ultra-low-flow bypass. Methods: Twenty-four piglets were randomly assigned to three bypass groups at risk for postoperative cerebral and renal dysfunction. Cerebral microcirculation was assessed by intravital microscopy. Rhodamine-stained leukocytes were observed for adhesion and rolling. Animals were randomized to one of four aprotinin doses. Neurological deficit score, histological score, creatinine and blood urea nitrogen were analyzed, both independently for this study as well as in combination with 50 animals who were studied with the same protocol and near-infrared spectroscopy. Results: There was a dose-dependent relationship, resulting in fewer activated rolling leukocytes with a higher aprotinin dose. Aprotinin dose was an independent predictor of more rapid recovery of neurological and behavioral outcome. We present a linear regression model where aprotinin dose predicts neurological score. Aprotinin had no impact on renal function. Conclusions: Aprotinin reduces cerebral leukocyte activation and accelerates neurologic recovery in a dose-dependent fashion. Aprotinin has no measurable impact on standard indices of renal function in young piglets. The current lack of availability of aprotinin is a serious disadvantage for pediatric patients undergoing cardiopulmonary bypass.