title: Suppression of cerebral metabolic rate for oxygen (CMRO2) by mild hypothermia compared with thiopental.
abstract: If the efficacy of hypothermia and barbiturates in ameliorating ischemic brain injury lies in reducing the cerebral metabolic rate of oxygen (CMRO2), the greater efficacy of mild hypothermia (34 degrees C) compared with barbiturates is inconsistent with the 15-20% reduction of CMRO2 caused by mild hypothermia compared with 50% caused by barbiturates. This paradox, we hypothesized, derives from the fact that whereas barbiturates lower CMRO2 associated with EEG activity or thiopental (TP)-suppressible CMRO2, not essential for cellular viability, hypothermia lowers CMRO2 associated with providing energy, i.e., adenosine triphosphate, to maintain transmembrane ion gradients or TP-nonsuppressible CMRO2, essential for neuronal viability. To test this hypothesis, we measured whole brain cerebral blood flow (CBF) and CMRO2 in two groups of rats mechanically ventilated with 70% N2O/30% O2 before and after TP-induced isoelectric EEG. In the normothermic group (n = 7), measurements were made at a brain temperature (Tb) 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 CMRO2 by 50%, from 7.92 +/- 1.05 to 3.95 +/- 0.70 ml 100 g-1 min-1 (mean +/- = SD). Thus, at 38 degrees C, TP-suppressible and TP-nonsuppressible CMRO2 were both 50 +/- 4% of total CMRO2. In the hypothermic group, decreasing Tb from 38 to 34 degrees C caused a 17% decline in CMRO2, 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 CMRO2 to 2.15 = 0.46 ml 100 g-1 min-1. At 34 degrees C, TP-suppressible and TP-nonsuppressible CMRO2 values were 64 +/- 7% and 36 +/- 8% of total CMRO2, respectively. TP lowered CBF by 50% at both 38 and 34 degrees C. In conclusion, mild hypothermia selectively lowers TP-nonsuppressible CMRO2 associated with the maintenance of viability rather than EEG-associated or TP-suppressible CMRO2.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh School of Medicine, PA 15261, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Nemoto
authors.forename: R
authors.initials: R
authors.lastname: Klementavicius
authors.forename: J A
authors.initials: JA
authors.lastname: Melick
authors.forename: H
authors.initials: H
authors.lastname: Yonas
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001481:Basal Metabolism / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007036:Hypothermia, Induced; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013874:Thiopental / Q000494:pharmacology*
chemical_list: D018686:Anesthetics, Intravenous; D013874:Thiopental; D010100:Oxygen