Altered Gene Expression Following Cardiopulmonary Bypass and Circulatory Arrest

Abstract

This study investigated the effects of normothermic cardiopulmonary bypass (CPB) and circulatory arrest (DHCA) on expression of specific genes in neonatal piglet brain. CPB was performed through the chest at 100 ml/kg/min for 2 hrs at 37°C. In the second group of animals, CPB was begun as described above and then animals were cooled to a nasopharyngeal/brain temperature of 18°C. When the brain temperature reached I8°C, the CPB circuit was turned off. After 60 min of circulatory arrest (DHCA), CPB was resumed at 100 ml/kg/min, and the piglets were rewarmed to a temperature of 36°C. In both groups, the animals remain sedated, paralyzed, mechanically ventilated, and continuously monitored throughout a four hour study period after CPB. Oxygen pressure in the microvasculature of the cortex was measured by oxygen dependent quenching of phosphorescence. The aRNA technique was used to assess mRNA steady-state levels in the brain tissue.

Control oxygen pressure (pre-bypass) was 61 ± 5 Torr and during CPB this decreased to 32 ± 7 Torr on the beginning of bypass and to 36 ± 5 Ton at the end of bypass. During the recovery period, cortical oxygenation steadily decreased, reaching 29 ± 8 Ton at the end of the four hours period. Cortical oxygen decreased during DHCA to near zero and during rewarming and recovery increased to 35 ± 6 Torr.

Measurements of gene expression following CPB revealed significantly increased levels of mRNA for NMDAR1, DARPP-32, CamKII, GluR1, and D1AR. DHCA caused changes similar to those for CPB in levels of mRNA for NMDAR1, DARPP-32, CamKII and GluRl. In contrast, DHCA caused significantly increased levels of mRNA for GluR6 and GABRB1. There was no significant alteration in the level of D1AR following DHCA.

The results showed that DHCA caused much larger alterations in gene expression in the critical metabolic signaling pathways tested than did CPB.