Effect of deep hypothermic circulatory arrest followed by low-flow cardiopulmonary bypass on brain metabolism in newborn piglets: comparison of pH-stat and α-stat management.

ABSTRACT

OBJECTIVE: To compare the effects of pH-stat and α-stat management before deep hypothermic circulatory arrest followed by a period of low-flow (two rates) cardiopulmonary bypass on cortical oxygenation and selected regulatory proteins Bax, Bcl-2, Caspase-3, and phospho-Akt. DESIGN: Piglets were placed on cardiopulmonary bypass, cooled with pH-stat or α-stat management to 18 °C over 30 mins, subjected to 30-min deep hypothermic circulatory arrest and 1-hr low flow at 20 mL/kg/min (LF-20) or 50 mL/kg/min (LF-50), rewarmed to 37 °C, separated from cardiopulmonary bypass, and recovered for 6 hrs. SUBJECTS: Newborn piglets, 2-5 days old, assigned randomly to experimental groups. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cortical oxygen was measured by oxygen-dependent quenching of phosphorescence; proteins were measured by Western blots. The means from six experiments ± sem are presented as % of α-stat. Significance was determined by Student's t test. For LF-20, cortical oxygenation was similar for α-stat and pH-stat, whereas for LF-50, it was significantly better using pH-stat. For LF-20, the measured proteins were not different except for Bax in the cortex (214 ± 24%, p = .006) and hippocampus (118 ± 6%, p = .024) and Caspase 3 in striatum (126% ± 7%, p = .019). For LF-50, in pH-stat group In cortex, Bax and Caspase-3 were lower (72 ± 8%, p = .001 and 72 ± 10%, p = .004, respectively) and pAkt was higher (138 ± 12%, p = .049). In hippocampus, Bcl-2 and Bax were not different but pAkt was higher (212 ± 37%, p = .005) and Caspase 3 was lower (84 ± 4%, p = .018). In striatum, Bax and pAkt did not differ, but Bcl-2 increased (146 ± 11%, p = .001) and Caspase-3 decreased (81 ± 11%, p = .042). CONCLUSIONS: In this deep hypothermic circulatory arrest-LF model, when flow was 20 mL/kg/min, there was little difference between α-stat and pH-stat management. However, for LF-50, pH-stat management resulted in better cortical oxygenation during recovery and Bax, Bcl-2, pAk, and Caspase-3 changes were consistent with lesser activation of proapoptotic signaling with pH-stat than with α-stat.