Effects of Phentolamine Infusion During Selective Cerebral Perfusion in Neonatal Piglets

Abstract

An optimal selective cerebral perfusion protocol in pediatric cardiac surgery is unknown. Phentolamine is frequently used in pediatric cardiopulmonary bypass. We sought to determine the effects of continuous phentolamine infusion during selective cerebral perfusion. Twenty-seven neonatal piglets (3.38 ± 0.32 kg) were randomly assigned to 3 groups; sham (n= 7, anesthesia alone, no surgery or bypass), control (n= 10, saline infusion), or experimental (n= 10, phentolamine infusion 0.1 mg/kg per hour). Animals underwent 90 minutes of selective cerebral perfusion. Cerebral vascular resistance index (CVRI) and metabolic rate of oxygen (CMRO2) were determined every 15 minutes. Standardized sections of hippocampus, basal ganglia, and neo-cortex were obtained. Tissue samples were stained for caspase-3 and analyzed for positive apoptotic cell count. Data were analyzed with repeated measures and one-way analysis of variance. The CVRI tended to increase over time in the control group and decrease over time in the experimental group, but difference was not statically significant (0.46 ± 0.24 vs 0.39 ± 0.10 mm Hg× min× kg(2/3)/mL, p= 0.15). Mean CMRO2 was higher in the control group compared with the experimental group (0.90 ± 0.27 vs 0.59 ± 0.12 mLO2/min× kg(2/3), p= 0.005) and decreased over time in both groups. The percentage of caspase-3 positive cells was significantly different among regions (hippocampus= 16.9 ± 8.8; basal ganglia= 14.6 ± 7.5; neocortex= 10.8 ± 6.3; p < 0.0001) but not significantly different among sham (11.8% ± 2.68%), control (14.4% ± 2.24%), and experimental (15.5% ± 2.24%) groups. A continuous infusion of phentolamine during selective cerebral perfusion significantly decreases CMRO2 and tends to decrease CVRI when compared with control. At the dose studied and at the time of tissue sampling, phentolamine does not appear to decrease apoptosis during or early after selective cerebral perfusion.