title: Norepinephrine activation of basal cerebral metabolic rate for oxygen (CMRO2) during hypothermia in rats.
abstract: In an earlier study on the effect of mild hypothermia (34 degrees C) on the cerebral metabolic rate for oxygen (CMRO2) in rats, we used norepinephrine (NE) to support arterial blood pressure while inducing isoelectricity on the electroencephalogram (EEG) with thiopental (TP). Even with administration of sufficient TP to reduce a fully active EEG to an isoelectric EEG, CMRO2 was often unchanged. Based on this observation, we hypothesized that NE had activated CMRO2 despite thiopental coma. Therefore, we studied the effect of NE compared with donor blood (DB) infusion to maintain arterial blood pressure during TP-induced isoelectric EEG on whole-brain CBF (H2 clearance) and CMRO2 during normothermia (38 degrees C) and mild hypothermia (34 degrees C) in rats during 70% N2O/30% O2 analgesia. Cerebral blood flow (CBF) and CMRO2 were measured in four groups of rats at 38 degrees C followed by measurements at either 38 degrees C (two groups) or 34 degrees C (two groups) and during TP-induced EEG isoelectricity. Within each of the two groups at 38 degrees C and 34 degrees C, arterial pressure was sustained by either DB (n = 10) or NE (n = 9) infusion. At 38 degrees C, CMRO2 in the DB and NE groups was 7.92 +/- 1.05 and 6.4 +/- 0.80 mL x 100 g-1.min-1 and decreased to 50% of normal (3.95 +/- 0.70 and 3.32 +/- 0.40 mL x 100 g-1.min-1, respectively) during TP isoelectricity for a functional:basal CMRO2 distribution of 50% +/- 4% and 50% +/- 4%. At 34 degrees C, CMRO2 values in the DB and NE groups were 6.31 +/- 1.41 and 5.41 +/- 2.02 mL x 100 g-1.min-1, respectively. During TP-induced isoelectricity, CMRO2 values in both groups were reduced to 2.37 +/- 0.43 and 3.55 +/- 1.27 mL x 100g-1.min-1, respectively, resulting in a functional:basal CMRO2 distribution of 61%:38% in the DB group and the reverse, or 27%:73%, in the Ne group. Basal CMRO2 was significantly (P < 0.05) larger in the NE-infused rats. These results suggest that NE infusion, by increasing CMRO2 during mild hypothermia, could nullify its protective effects in the ischemic brain.
authors.affiliation: Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pennsylvania, 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: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage; D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001803:Blood Transfusion; D001831:Body Temperature; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002545:Brain Ischemia / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003128:Coma / Q000139:chemically induced / Q000503:physiopathology; D004569:Electroencephalography / Q000187:drug effects; D007035:Hypothermia / Q000378:metabolism*; D007036:Hypothermia, Induced; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D009609:Nitrous Oxide / Q000008:administration & dosage; D009638:Norepinephrine / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013874:Thiopental / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D018696:Neuroprotective Agents; D013874:Thiopental; D009609:Nitrous Oxide; D009638:Norepinephrine