title: Fetal brain hypometabolism during prolonged hypoxaemia in the llama.
abstract: In this study we looked for additional evidence to support the hypothesis that fetal llama reacts to hypoxaemia with adaptive brain hypometabolism. We determined fetal llama brain temperature, Na(+) and K(+) channel density and Na(+)-K(+)-ATPase activity. Additionally, we looked to see whether there were signs of cell death in the brain cortex of llama fetuses submitted to prolonged hypoxaemia. Ten fetal llamas were instrumented under general anaesthesia to measure pH, arterial blood gases, mean arterial pressure, heart rate, and brain and core temperatures. Measurements were made 1 h before and every hour during 24 h of hypoxaemia (n = 5), which was imposed by reducing maternal inspired oxygen fraction to reach a fetal arterial partial pressure of oxygen (P(a,O(2))) of about 12 mmHg. A normoxaemic group was the control (n = 5). After 24 h of hypoxaemia, we determined brain cortex Na(+)-K(+)-ATPase activity, ouabain binding, and the expression of NaV1.1, NaV1.2, NaV1.3, NaV1.6, TREK1, TRAAK and K(ATP) channels. The lack of brain cortex damage was assessed as poly ADP-ribose polymerase (PARP) proteolysis. We found a mean decrease of 0.56 degrees C in brain cortex temperature during prolonged hypoxaemia, which was accompanied by a 51% decrease in brain cortex Na(+)-K(+)-ATPase activity, and by a 44% decrease in protein content of NaV1.1, a voltage-gated Na(+) channel. These changes occurred in absence of changes in PARP protein degradation, suggesting that the cell death of the brain was not enhanced in the fetal llama during hypoxaemia. Taken together, these results provide further evidence to support the hypothesis that the fetal llama responds to prolonged hypoxaemia with adaptive brain hypometabolism, partly mediated by decreases in Na(+)-K(+)-ATPase activity and expression of NaV channels.
authors.affiliation: Programa de Fisiopatología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago.
authors.forename: Germán
authors.initials: G
authors.lastname: Ebensperger
authors.forename: Renato
authors.initials: R
authors.lastname: Ebensperger
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Herrera
authors.forename: Raquel A
authors.initials: RA
authors.lastname: Riquelme
authors.forename: Emilia M
authors.initials: EM
authors.lastname: Sanhueza
authors.forename: Florian
authors.initials: F
authors.lastname: Lesage
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Marengo
authors.forename: Rodrigo I
authors.initials: RI
authors.lastname: Tejo
authors.forename: Aníbal J
authors.initials: AJ
authors.lastname: Llanos
authors.forename: Roberto V
authors.initials: RV
authors.lastname: Reyes
mesh_terms: D000818:Animals; D001831:Body Temperature; D001921:Brain / Q000196:embryology / Q000201:enzymology / Q000378:metabolism*; D002161:Camelids, New World / Q000196:embryology / Q000378:metabolism* / Q000502:physiology; D002540:Cerebral Cortex / Q000196:embryology / Q000201:enzymology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010042:Ouabain / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D015222:Sodium Channels; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase