Abstract 10894: Cerebral Energy Metabolism and Pools of Neurotransmitters Related to the Use of Deep Hypothermic Circulatory Arrest in Infant Piglets

Abstract

Introduction: Complex congenital cardiac defect repair in infants often requires deep hypothermic circulatory arrest (DHCA). As immediate or late neurological complications still occur, adjunctive selective cerebral perfusion (SCP) theoretically provides superior neural protection by supplying oxygen and substrate and maintaining energy metabolism. Hypothesis: SCP preserves glucose utilization, energy metabolism, and glutamate cycling in comparison to DHCA alone. Methods: Fourteen male Yorkshire piglets (age 34-44 days) were assigned randomly to 2 groups (DHCA or SCP for 60 minutes at 18°C). Cerebral perfusion through 1st branch of aorta was maintained at 40 ml/kg/min during SCP. After the completion of rewarming, 13-Carbon-labeled glucose ( 13 C-glucose) was infused through common carotid artery for 1 hour under continuous cardiopulmonary bypass support and then cerebral tissue was extracted. Gas chromatography-mass spectrometry and nuclear magnetic resonance were used for cerebral metabolic analysis in the frontal cortex of brain. Results: There were no operative or technical complications in any groups. Cerebral rSO 2 in simple DHCA dropped substantially to ~ 25% during DHCA, but maintained over 80% in SCP. Apoptosis by TUNEL assay was significantly less in SCP at 2.5 hours after DHCA. ATP levels in the extracted cerebral tissue were similar between 2 groups but glycogen store were higher in SCP. Absolute levels of lactate and citric acid cycle intermediates and their 13 C-enrichment were similar in the cerebral tissue between the 2 groups. However, SCP increased absolute and 13 C-enrichment for glutamate and compared to DHCA, while gamma aminobutyric acid (GABA) increased in DHCA. Conclusions: SCP added to DHCA does not provide additional ATP preservation or modify glucose oxidation. However, SCP does alter glucose cycling into alternate pathways, leading to preservation of glycogen, and shifts flux away from GABA, a major inhibitory neurotransmitter, and towards glutamate. These flux changes suggest that SCP decreases synaptic inhibition, which may relate to the reduced neural apoptosis.