Suppression of cerebral metabolic rate for oxygen (CMRO(2)) by mild hypothermia compared with thiopental

If the efficacy of hypothermia and barbiturates in ameliorating ischemic brain injury lies in reducing the cerebral metabolic rate of oxygen (CMRO(2)), the greater efficacy of mild hypothermia (34 degrees C) compared with barbiturates is inconsistent with the 15-20% reduction of CMRO(2) caused by mild hypothermia compared with 50% caused by barbiturates. This paradox, we hypothesized, derives from the fact that whereas barbiturates lower CMRO(2) associated with EEG activity or thiopental (TP)-suppressible CMRO(2), not essential for cellular viability, hypothermia lowers CMRO(2) associated with providing energy, i.e., adenosine triphosphate, to maintain transmembrane ion gradients or TP-nonsuppressible CMRO(2), essential for neuronal viability. To test this hypothesis, we measured whole brain cerebral blood flow (CBF) and CMRO(2) in two groups of rats mechanically ventilated with 70% N2O/30% O-2 before and after TP-induced isoelectric EEG. In the normothermic group (n = 7), measurements were made at a brain temperature (T-b) of 38 degrees C, while in the hypothermic group (n = 7), they were made at 34 degrees C. In the normothermic group, TP-induced isoelectric EEG reduced CMRO(2) by 50%, from 7.92 +/- 1.05 to 3.95 +/- 0.70 ml 100 g(-1) min(-1) ((X) over bar +/- SD). Thus, at 38 degrees C, TP-suppressible and TP-nonsuppressible CMRO(2) were both 50 +/- 4% of total CMRO(2). In the hypothermic group, decreasing T-b from 38 to 34 degrees C caused a 17% decline in CMRO(2), from 7.62 +/- 1.92 to 6.28 +/- 1.22 ml 100 g(-1) min(-1) (p > 0.05). AT 34 degrees C, TP infusion lowered CMRO(2) to 2.15 +/- 0.46 ml 100 g(-1) min(-1). At 34 degrees C, TP-suppressible and TP-nonsuppressible CMRO(2) values were 64 +/- 7% and 36 +/- 8% of total CMRO(2), respectively. TP lowered CBF by 50% at both 38 and 34 degrees C. In conclusion, mild hypothermia selectively lowers TP-nonsuppressible CMRO(2) associated with the maintenance of viability rather than EEG-associated or TP-suppressible CMRO(2).