The Circulatory Arrest Recovery Ammonia Problem (CARAP) Hypothesis: a 1H-MRS study of brain metabolism during neonatal cardiopulmonary bypass surgery.

Abstract

Objective: Congenital heart disease affects 1% of US births, with many babies requiring major cardiothoracic surgery under cardiopulmonary bypass (CPB), exposing the more critical patients to neurodevelopmental impairment. Optimal surgical parameters to minimize neuronal injury are unknown. We used ¹H MRS and blood ammonia assays in a neonatal pig model of CPB to compare two approaches, complete circulatory arrest (CA) versus antegrade cerebral perfusion (ACP).

Methods: Two-week old piglets (N=17) were put on a CPB pump and placed in a 3T MRI to study brain metabolism during CPB. Dynamic single-voxel ¹H MRS brain data were acquired while animals underwent one of four CPB protocols: ∼50 min CA at 18ºC and 28ºC or ACP at 18ºC and 28ºC, followed by a ∼1-hr recovery period. Based on ¹H MRS findings suggesting the presence of brain ammonia upon reperfusion, a second cohort of piglets (N=22) underwent the same CPB conditions without MRS to allow regular venous blood sampling with ammonia assays.

Results: All animals showed a transitory temperature-dependent rise in blood ammonia (p < .001) immediately following restart of whole-body perfusion . In contrast, metabolic processing of brain ammonia, as detected by an increased ¹H MRS glutamine/glutamate ratio, was also temperature dependent (p =.002) but only significantly observed in the CA studies (p =.009).

Conclusions: Serial ¹H-MRS and blood ammonia assays in this preclinical CPB model identified a previously unreported build-up of ammonia, hypothesized to arise from gut bacterial production, following reperfusion, that may contribute to brain injury in these pediatric surgeries.