title: Diazoxide Attenuates Postresuscitation Brain Injury in a Rat Model of Asphyxial Cardiac Arrest by Opening Mitochondrial ATP-Sensitive Potassium Channels.
abstract: Objective. We investigated whether and how diazoxide can attenuate brain injury after cardiopulmonary resuscitation (CPR) by selective opening of mitochondrial ATP-sensitive potassium (mitoKATP) channels. Methods. Adult male Sprague-Dawley rats with induced cerebral ischemia (n = 10 per group) received an intraperitoneal injection of 0.1% dimethyl sulfoxide (1 mL; vehicle group), diazoxide (10 mg/kg; DZ group), or diazoxide (10 mg/kg) plus 5-hydroxydecanoate (5 mg/kg; DZ + 5-HD group) 30 min after CPR. The control group (sham group, n = 5) underwent sham operation, without cardiac arrest. Mitochondrial respiratory control rate (RCR) was determined. Brain cell apoptosis was assessed using TUNEL staining. Expression of Bcl-2, Bax, and protein kinase C epsilon (PKCε) in the cerebral cortex was determined by Western blotting and immunohistochemistry. Results. The neurological deficit scores (NDS) in the vehicle group decreased significantly at 24 h and 48 h after CPR. Diazoxide significantly improved NDS and mitochondrial RCR after CPR at both time points; 5-HD cotreatment abolished these effects. Diazoxide decreased TUNEL-positive cells following CPR, upregulated Bcl-2 and PKCε, downregulated Bax, and increased the Bcl-2/Bax ratio; 5-HD cotreatment reversed these effects. Conclusions. Diazoxide attenuates postresuscitation brain injury, protects mitochondrial function, inhibits brain cell apoptosis, and activates the PKC pathway by opening mitoKATP channels.
authors.affiliation: Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China.
authors.forename: Haidong
authors.identifier: 0000-0003-2858-4733
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China.
authors.forename: Manhui
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zitong
authors.identifier: 0000-0001-7936-4963
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000201:enzymology / Q000628:therapy*; D001930:Brain Injuries / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control; D002540:Cerebral Cortex / Q000201:enzymology; D003981:Diazoxide / Q000494:pharmacology*; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000201:enzymology / Q000628:therapy*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000009:adverse effects*
chemical_list: D009419:Nerve Tissue Proteins; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D003981:Diazoxide