title: Hypothermia-induced neuroprotection is associated with reduced mitochondrial membrane permeability in a swine model of cardiac arrest.
abstract: Increasing evidence has shown that mild hypothermia is neuroprotective for comatose patients resuscitated from cardiac arrest, but the mechanism of this protection is not fully understood. The aim of this study was to determine whether prolonged whole-body mild hypothermia inhibits mitochondrial membrane permeability (MMP) in the cerebral cortex after return of spontaneous circulation (ROSC). Thirty-seven inbred Chinese Wuzhishan minipigs were successfully resuscitated after 8 minutes of untreated ventricular fibrillation (VF) and underwent recovery under normothermic (NT) or prolonged whole-body mild hypothermic (HT; 33°C) conditions for 24 or 72 hours. Cerebral samples from the frontal cortex were collected at 24 and 72 hours after ROSC. Mitochondria were isolated by differential centrifugation. At 24 hours, relative to NT, HT was associated with reductions in opening of the mitochondrial permeability transition pore, release of pro-apoptotic substances from mitochondria, caspase 3 cleavage, apoptosis, and neurologic deficit scores, as well as increases in mitochondrial membrane potential and mitochondrial respiration. Together, these findings suggest that mild hypothermia inhibits ischemia-induced increases in MMP, which may provide neuroprotection against cerebral injury after cardiac arrest.
authors.affiliation: Department of Emergency, First Hospital affiliated to Dalian Medical University, Dalian, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
authors.forename: Rong
authors.initials: R
authors.lastname: Hua
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Ziren
authors.initials: Z
authors.lastname: Tang
authors.forename: Xue
authors.initials: X
authors.lastname: Mei
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Cui
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D016887:Cardiopulmonary Resuscitation; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006323:Heart Arrest / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D006439:Hemodynamics; D007036:Hypothermia, Induced; D008297:Male; D053078:Membrane Potential, Mitochondrial; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism* / Q000473:pathology; D000083162:Mitochondrial Permeability Transition Pore; D010100:Oxygen / Q000378:metabolism; D010539:Permeability; D013552:Swine; D013556:Swine, Miniature; D014693:Ventricular Fibrillation / Q000378:metabolism / Q000473:pathology / Q000628:therapy
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D053148:Caspase 3; D010100:Oxygen