title: Mild hypothermia inhibits systemic and cerebral complement activation in a swine model of cardiac arrest.
abstract: Complement activation has been implicated in ischemia/reperfusion injury. This study aimed to determine whether mild hypothermia (HT) inhibits systemic and cerebral complement activation after resuscitation from cardiac arrest. Sixteen minipigs resuscitated from 8 minutes of untreated ventricular fibrillation were randomized into two groups: HT group (n=8), treated with HT (33°C) for 12 hours; and normothermia group (n=8), treated similarly as HT group except for cooling. Blood samples were collected at baseline and 0.5, 6, 12, and 24 hours after return of spontaneous circulation (ROSC). The brain cortex was harvested 24 hours after ROSC. Complement and pro-inflammatory markers were detected using enzyme-linked immunosorbent assay. Neurologic deficit scores were evaluated 24 hours after ROSC. C1q, Bb, mannose-binding lectin (MBL), C3b, C3a, C5a, interleukin-6, and tumor necrosis factor-α levels were significantly increased under normothermia within 24 hours after ROSC. However, these increases were significantly reduced by HT. Hypothermia decreased brain C1q, MBL, C3b, and C5a contents 24 hours after ROSC. Hypothermic pigs had a better neurologic outcome than normothermic pigs. In conclusion, complement is activated through classic, alternative, and MBL pathways after ROSC. Hypothermia inhibits systemic and cerebral complement activation, which may provide an additional mechanism of cerebral protection.
authors.affiliation: Department of Emergency, First Hospital affiliated to Dalian Medical University, Dalian, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
authors.affiliation: Department of Emergency, Beijing Chaoyang Hospital affiliated to Capital Medical University, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Emergency, Beijing Chaoyang Hospital affiliated to Capital Medical University, Beijing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Hua
authors.affiliation: Department of Emergency, Beijing Chaoyang Hospital affiliated to Capital Medical University, Beijing, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Emergency, Beijing Chaoyang Hospital affiliated to Capital Medical University, Beijing, China.
authors.forename: Ziren
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Emergency, Beijing Chaoyang Hospital affiliated to Capital Medical University, Beijing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Mei
authors.affiliation: Department of Emergency, Beijing Chaoyang Hospital affiliated to Capital Medical University, Beijing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Emergency, Beijing Chaoyang Hospital affiliated to Capital Medical University, Beijing, China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003167:Complement Activation; D003165:Complement System Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000097:blood* / Q000473:pathology / Q000628:therapy*; D007036:Hypothermia, Induced; D013552:Swine; D013997:Time Factors
chemical_list: D003165:Complement System Proteins