Molecular mechanisms of therapeutic hypothermia on neurological function in a swine model of cardiopulmonary resuscitation.
Resuscitation
; 83(7): 913-20, 2012 Jul.
Article
en En
| MEDLINE
| ID: mdl-22245747
ABSTRACT
OBJECTIVE:
To explore the molecular mechanisms by which mild hypothermia following resuscitation improves neurological function in a porcine model of cardiac arrest.METHODS:
Thirty-three inbred Chinese Wuzhishan (WZS) minipigs were used. After 8 min of untreated ventricular fibrillation (VF), the surviving animals (n=29) were randomly divided into two groups including serum group (n=16) and molecular group (n=13). Serum group animals were used to measure porcine-specific tumour necrosis factor-alpha (TNF-α), interleukin (IL-6, IL-10), matrix metalloproteinase (MMP9), Aquaporin-4 (AQP4), tissue inhibitor to metalloproteinase-1 (TIMP1), neuron-specific enolase (NSE) and S100B at 0.5 h, 6 h, 12 h, 24 h and 72h recovery by enzyme-linked immunosorbent assay (ELISA). Molecular group animals were used to measure cerebral cortex messenger RNA (mRNA) and protein expression of nuclear factor-κB (NF-κB), MMP9 and AQP4 by real-time (RT) quantitative polymerase chain reaction (PCR) and Western blotting at 24 h and 72 h recovery. Animals were further divided into either normothermia or hypothermia groups. Hypothermia (33°C) was maintained for 12 h using an endovascular cooling device. Swine neurologic deficit scores (NDS) were used to evaluate neurological function at 24-h and 72-h recovery.RESULTS:
Twenty-nine of the 33 (87.9%) animals were successfully resuscitated. The hypothermia group exhibited higher survival rates at 24 h (75%) and 72 h (62.5%) compared to the normothermia group (37.5% and 25%, respectively). Hypothermia markedly inhibited expression of NF-κB, TNF-α, MMP9 and NSE, and promoted expression of TIMP1 (P<0.01). The mean NDS at 24-h and 72-h recovery was 112.5 and 61, respectively, in the hypothermic group, and 230 and 207.5, respectively, in the normothermia group.CONCLUSION:
Brain protection induced by hypothermia involves inhibition of inflammatory and brain edema pathways.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fibrilación Ventricular
/
Citocinas
/
Reanimación Cardiopulmonar
/
Paro Cardíaco
/
Hipotermia Inducida
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Resuscitation
Año:
2012
Tipo del documento:
Article
País de afiliación:
China