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Targeted Temperature Management Suppresses Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor Expression in a Pig Model of Cardiac Arrest.

Authors
  • Li, Jiebin1
  • Li, Chunsheng2
  • Yuan, Wei3
  • Wu, Junyuan3
  • Li, Jie4
  • Li, Zhenhua5
  • Zhao, Yongzhen3
  • 1 Department of Emergency Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China. , (China)
  • 2 Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng, Beijing, 100050, China. [email protected] , (China)
  • 3 Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China. , (China)
  • 4 Department of Emergency Medicine, Beijing Fuxing Hospital, Capital Medical University, Beijing, 100038, China. , (China)
  • 5 Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng, Beijing, 100050, China. , (China)
Type
Published Article
Journal
Neurocritical care
Publication Date
Jan 05, 2021
Identifiers
DOI: 10.1007/s12028-020-01166-0
PMID: 33403582
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor subtype 2 (VEGFR-2) pathway has been implicated in ischemia/reperfusion injury. The aim of this study was to clarify whether whole-body hypothermic targeted temperature management (HTTM) inhibits the HIF-1α/VEGF/VEGFR-2 pathway in a swine model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Twenty-four domestic male Beijing Landrace pigs were used in this study. CA was electrically induced with ventricular fibrillation and left untreated for 8 min. Return of spontaneous circulation (ROSC) was achieved in 16 pigs, which were randomly assigned either to normothermia at 38 °C or to HTTM at 33 °C (each group: n = 8). HTTM was intravascularly induced immediately after ROSC. The core temperature was reduced to 33 °C and maintained for 12 h after ROSC. The serum levels of HIF-1α, VEGF, VEGFR-2, and neuron-specific enolase (NSE) were measured with enzyme immunoassay kits 0.5, 6, 12, and 24 h after ROSC. The expression of HIF-1α, VEGF, and VEGFR-2 in cerebral cortical tissue was measured by RT-PCR and Western blot analysis 24 h after ROSC. Neurological deficit scores and brain cortical tissue water content were evaluated 24 h after ROSC. The serum levels of HIF-1α, VEGF, and VEGFR-2 were significantly increased under normothermia within 24 h after ROSC. However, these increases were significantly reduced by HTTM. HTTM also decreased cerebral cortical HIF-1α, VEGF, and VEGFR-2 mRNA and protein expression 24 h after ROSC (all p < 0.05). HTTM pigs had better neurological outcomes and less brain edema than normothermic pigs. The HIF-1α/VEGF/VEGFR-2 system is activated following CA and CPR. HTTM protects against cerebral injury after ROSC, which may be part of the mechanism by which it inhibits the expression of components of the HIF-1α/VEGF/VEGFR-2 signaling pathway.

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