Xenon Augmented Hypothermia Reduces Early Lactate/N-Acetylaspartate and Cell Death in Perinatal Asphyxia

被引：91

作者：

Faulkner, Stuart ^{[1
]}

Bainbridge, Alan ^{[2
]}

Kato, Takenori ^{[1
]}

Chandrasekaran, Manigandan ^{[1
]}

Kapetanakis, Andrew B. ^{[1
]}

Hristova, Mariya ^{[1
]}

Liu, Mengyan ^{[1
]}

Evans, Samantha ^{[1
]}

De Vita, Enrico ^{[2
]}

Kelen, Dorottya ^{[1
]}

Sanders, Robert D. ^{[3
,4
,5
]}

Edwards, A. David ^{[6
,7
]}

Maze, Mervyn ^{[8
]}

Cady, Ernest B. ^{[2
]}

Raivich, Gennadij ^{[1
]}

Robertson, Nicola J. ^{[1
]}

机构：

[1] UCL, Inst Womens Hlth, London WC1E 6HX, England

[2] Univ Coll London Hosp, London, England

[3] Univ London Imperial Coll Sci Technol & Med, Dept Anesthet, London, England

[4] Univ London Imperial Coll Sci Technol & Med, Dept Intens Care, London, England

[5] Univ London Imperial Coll Sci Technol & Med, Dept Biol Sci, London, England

[6] Univ London Imperial Coll Sci Technol & Med, Inst Clin Sci, London, England

[7] MRC, Ctr Clin Sci, London, England

[8] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA

来源：

ANNALS OF NEUROLOGY | 2011年 / 70卷 / 01期

基金：

英国医学研究理事会;

关键词：

MAGNETIC-RESONANCE-SPECTROSCOPY; HYPOXIC-ISCHEMIC ENCEPHALOPATHY; CEREBRAL ENERGY FAILURE; CALCULATING CORRELATION-COEFFICIENTS; MILD SYSTEMIC HYPOTHERMIA; LEFT-VENTRICULAR FUNCTION; NEONATAL ENCEPHALOPATHY; NEWBORN PIGLET; MODERATE HYPOTHERMIA; THERAPEUTIC HYPOTHERMIA;

D O I：

10.1002/ana.22387

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective: Additional treatments for therapeutic hypothermia are required to maximize neuroprotection for perinatal asphyxial encephalopathy. We assessed neuroprotective effects of combining inhaled xenon with therapeutic hypothermia after transient cerebral hypoxia-ischemia in a piglet model of perinatal asphyxia using magnetic resonance spectroscopy (MRS) biomarkers supported by immunohistochemistry. Methods: Thirty-six newborn piglets were randomized (all groups n = 9), with intervention from 2 to 26 hours, to: (1) normothermia; (2) normothermia + 24 hours 50% inhaled xenon; (3) 24 hours hypothermia (33.5 degrees C); or (4) 24 hours hypothermia (33.5 degrees C) + 24 hours 50% inhaled xenon. Serial MRS was acquired before, during, and up to 48 hours after hypoxia-ischemia. Results: Mean arterial blood pressure was lower in all treatment groups compared with normothermia (p < 0.01) (although >40mmHg); the combined therapy group required more fluid boluses (p < 0.05) and inotropes (p < 0.001). Compared with no intervention, both hypothermia and xenon-augmented hypothermia reduced the temporal regression slope magnitudes for phosphorus-MRS inorganic phosphate/exchangeable phosphate pool (EPP) and phosphocreatine/EPP (both p < 0.05); for lactate/N-acetylaspartate (NAA), only xenon-augmented hypothermia reduced the slope (p < 0.01). Xenon-augmented hypothermia also reduced transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)(+) nuclei and caspase 3 immunoreactive cells in parasagittal cortex and putamen and increased microglial ramification in midtemporal cortex compared with the no treatment group (p < 0.05). Compared with hypothermia, however, combination treatment did not reach statistical significance for any measure. Lactate/NAA showed a strong positive correlation with TUNEL; nucleotide triphosphate/EPP showed a strong negative correlation with microglial ramification (both p < 0.01). Interpretation: Compared with no treatment, xenon-augmented hypothermia reduced cerebral MRS abnormalities and cell death markers in some brain regions. Compared with hypothermia, xenon-augmented hypothermia did not reach statistical significance for any measure. The safety and possible improved efficacy support phase II trials. ANN NEUROL 2011;70:133-150

引用

页码：133 / 150

页数：18

共 64 条

[1] Magnetic resonance biomarkers of neuroprotective effects in infants with hypoxic ischemic encephalopathy [J].