title: Prolonged therapeutic hypothermia is more effective in attenuating brain apoptosis in a Swine cardiac arrest model.
abstract: OBJECTIVE
  To investigate whether 48 hours of therapeutic hypothermia is more effective to attenuate brain apoptosis than 24 hours and to determine whether the antiapoptotic effects of therapeutic hypothermia are associated with the suppressions of the cleavage of protein kinase C-δ, the cytosolic release of cytochrome c, and the cleavage of caspase 3 in a swine cardiac arrest model.
  
  
  METHODS
  Prospective laboratory study.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Male domestic pigs (n = 24).
  
  
  METHODS
  After 6 minutes of no-flow time that was induced by ventricular fibrillation, cardiopulmonary resuscitation was provided, and the return of spontaneous circulation was achieved. The animals were randomly assigned to the following groups: sham, normothermia, 24 hours of therapeutic hypothermia, or 48 hours of therapeutic hypothermia. Therapeutic hypothermia (core temperature, 32-34°C) was maintained for 24 or 48 hours post return of spontaneous circulation, and the animals were rewarmed for 8 hours. At 60 hours post return of spontaneous circulation, the animals were killed, and brain tissues were harvested.
  
  
  RESULTS
  We examined cellular apoptosis and neuronal damage in the brain hippocampal cornu ammonis 1 region. We also measured the cleavage of protein kinase C-δ, the cytosolic release of cytochrome c, and the cleavage of caspase 3 in the hippocampus. The 48 hours of therapeutic hypothermia attenuated cellular apoptosis and neuronal damage when compared with normothermia. There was also a decrease in the cleavage of protein kinase C-δ, the cytosolic release of cytochrome c, and the cleavage of caspase 3. However, 24 hours of therapeutic hypothermia did not significantly attenuate cellular apoptosis or neuronal damage.
  
  
  CONCLUSIONS
  We found that 48 hours of therapeutic hypothermia was more effective in attenuating brain apoptosis than 24 hours of therapeutic hypothermia. We also found that the antiapoptotic effects of therapeutic hypothermia were associated with the suppressions of the cleavage of protein kinase C-δ, the cytosolic release of cytochrome c, and the cleavage of caspase 3.
authors.affiliation: 1Department of Emergency Medicine, Seoul National University Hospital, Seoul, Republic of Korea. 2Department of Emergency Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea. 3Department of Emergency Medicine, National Medical Center, Seoul, Republic of Korea. 4Department of Emergency Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea.
authors.forename: Gil Joon
authors.initials: GJ
authors.lastname: Suh
authors.forename: Woon Yong
authors.initials: WY
authors.lastname: Kwon
authors.forename: Kyung Su
authors.initials: KS
authors.lastname: Kim
authors.forename: Hui Jai
authors.initials: HJ
authors.lastname: Lee
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Jeong
authors.forename: Yoon Sun
authors.initials: YS
authors.lastname: Jung
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000473:pathology*; D006323:Heart Arrest / Q000517:prevention & control*; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D013552:Swine; D013997:Time Factors