Abstract 2599: Aprotinin Protects the Cerebral Microcirculation during Cardiopulmonary Bypass
We have previously reported that administration of aprotinin at a single dose level protects the cerebral microcirculation. The current study explores the optimal dose for protection of the cerebral microcirculation as well as neurological and behavioral recovery after circulatory arrest and ultra low flow bypass. 24 piglets (age 4 weeks) were randomly assigned to three bypass groups at risk for postop cerebral and renal dysfunction: circulatory arrest at 25°C, ultra low flow (10 ml/kg/min) at 25 or 34°C. Animals were randomized to one of four aprotinin doses: no aprotinin, low dose (30000 KIU/kg into prime only), standard dose (30000 KIU/kg bolus IV into prime plus 10000 KIU/kg infusion), and double dose. Cerebral microcirculation was assessed by intravital microscopy through a cranial window. Rhodamine-stained leukocytes were observed in postcapillary venules, with analysis for adhesion and rolling. Neurological deficit score, histological score, creatinine and blood urea nitrogen were analyzed both independently for this study as well as in combination with 50 previously reported animals who were studied with the same protocol and near infrared spectroscopy rather than intravital microscopy. There was a dose dependent relationship between the number of adherent and rolling leukocytes with a higher aprotinin dose correlating with a lower number of activated white cells. Both independent analysis of this intravital microscopy study as well as combined analysis with animals undergoing near infrared spectroscopy in a previous study with the same bypass and aprotinin dose schedules confirm that aprotinin dose is an independent predictor of more rapid recovery of neurological and behavioral outcome. There is a linear dosage response model by which aprotinin predicts neurological score. Aprotinin was not predictive of histological score and had no impact on renal function. 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.