Brain oxygen and metabolism is dependent on the rate of low-flow cardiopulmonary bypass following circulatory arrest in newborn piglets

Objective: To determine the optimum rate of low-flow hypothermic cardiopulmonary bypass (LF), following circulatory arrest (DHCA) on brain oxygenation (bO₂), extracellular dopamine (DA), phosphorylation of select neuroregulatory proteins responsible for neuronal injury, and survival following ischemic brain injury: CREB, Erk1/2, Akt, Bcl-2, and Bax. Methods: The piglets were placed on cardiopulmonary bypass (CPB) and cooled to 18 °C. They were then subjected to 30 min of DHCA followed by 1 h of LF at 20, 50, or 80 ml/(kg/min), rewarmed, separated from CPB, and maintained for 2 h. The bO₂ was measured by quenching of phosphorescence; DA by microdialysis; phosphorylation of CREB, ERK1/2, Akt, Bcl-2, and Bax by Western blots. The results are means ± SD for seven experiments. Results: Pre-bypass bO₂ was 47.4 ± 4.2 mmHg and decreased to 1.9 ± 0.8 mmHg during DHCA. At the end of LF at 20, 50, and 80 ml/(kg/min), bO₂ was 11.8 ± 1.6, 26 ± 1.8, and 33.9 ± 2.6 mmHg, respectively. The DA increased 510-fold relative to control (p < 0.001) by 15 min of LF-20 with maximum increase occurring at 45 min. With LF-50, increase in DA was not statistically significant and no increase was observed when LF-80 was used. Bcl-2 immunoreactivity increased after LF-50 and LF-80 (140 ± 14.5%, p < 0.05 and 202 ± 34%, p < 0.05, respectively). Neither flow increased Bax immunoreactivity. The ratio of Bcl-2/Bax, pCREB, pAkt, pErk increased significantly with increasing the flow rate of LF. Conclusions: The protective effect of LF following DHCA on brain metabolism is dependent on the flow rate. Flow-dependent increase in pCREB, pErk1/2, pAkt, increase in Bcl-2/Bax, and decrease in DA indicated that to minimize DHCA-dependent neuronal injury, LF flow should be above 50 ml/(kg/min).