title: Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in Rats.
abstract: We previously have shown that glibenclamide (GBC), a sulfonylurea receptor 1-transient receptor potential M4 (SUR1-TRPM4) channel inhibitor, improves survival and neurological outcome after asphyxial cardiac arrest and cardiopulmonary resuscitation (ACA/CPR). Here, we further compare the efficacy of GBC with target temperature management (TTM) and determine whether the efficacy of GBC is affected by TTM.
  
  
  
  Male Sprague-Dawley rats (n=213) subjected to 10-minute ACA/CPR were randomized to 4 groups after return of spontaneous circulation (ROSC): normothermia control (NT); GBC; TTM; and TTM+GBC. Survival, neurodeficit scores, histological injury, as well as the expressions of SUR1 and TRPM4 were evaluated. The 7-day survival rate was 34.4% (11 of 32) in the NT group, 65% (13 of 20) in the GBC group, 50% (10 of 20) in the TTM group, and 70% (14 of 20) in the TTM+GBC group. Rats that received either GBC, TTM alone, or in combination showed less neurological deficit than NT control at 24, 48, and 72 hours and 7 days after ROSC. Moreover, TTM or GBC ameliorated neuronal degeneration and glial activation in the hippocampal CA1 region with similar efficacy, whereas the combination of them had a trend toward better effect. The subunits of SUR1-TRPM4 heterodimers were both strongly upregulated after ACA/CPR and expressed in multiple types of brain cells, but partly suppressed by TTM.
  
  
  
  GBC is comparable to TTM in improving survival and neurological outcome after ACA/CPR. When GBC is given along with TTM, less histological injury tended to be achieved.
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Kaibin
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ziyue
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zuoshan
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China pansuyue82@126.com.
authors.forename: Suyue
authors.initials: S
authors.lastname: Pan
mesh_terms: D000818:Animals; D001237:Asphyxia; D016887:Cardiopulmonary Resuscitation; D004195:Disease Models, Animal; D005905:Glyburide / Q000627:therapeutic use*; D006323:Heart Arrest / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007036:Hypothermia, Induced; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D005905:Glyburide
keywords: cardiopulmonary resuscitation; glibenclamide; heart arrest; sulfonylurea receptor 1‐transient receptor potential M4 channel; target temperature management