title: Impact of therapeutic hypothermia onset and duration on survival, neurologic function, and neurodegeneration after cardiac arrest.
abstract: OBJECTIVE
  Post-cardiac-arrest therapeutic hypothermia improves outcomes in comatose cardiac arrest survivors. This study tests the hypothesis that the efficacy of post-cardiac-arrest therapeutic hypothermia is dependent on the onset and duration of therapy.
  
  
  METHODS
  Prospective randomized laboratory investigation.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  A total of 268 male Long Evans rats.
  
  
  METHODS
  Post-cardiac-arrest therapeutic hypothermia.
  
  
  RESULTS
  Adult male Long Evans rats that achieved return of spontaneous circulation after a 10-min asphyxial cardiac arrest were block randomized to normothermia (37°C ± 1°C) or therapeutic hypothermia (33°C ± 1°C) initiated 0, 1, 4, or 8 hrs after return of spontaneous circulation and maintained for 24 or 48 hrs. Therapeutic hypothermia initiated 0, 1, 4, and 8 hrs after return of spontaneous circulation resulted in 7-day survival rates of 45%*, 36%*, 36%*, and 14%, respectively, compared to 17% for normothermic controls and survival with good neurologic function rates of 24%*, 24%*, 19%*, and 0%, respectively, compared to 2% for normothermic controls (*p < .05 vs. normothermia). These outcomes were not different when therapeutic hypothermia was maintained for 24 vs. 48 hrs. In contrast, hippocampal CA1 pyramidal neuron counts were 53% ± 27%*, 53% ± 19%*, 51% ± 24%*, and 65% ± 16%* of normal, respectively, when therapeutic hypothermia was initiated 0, 1, 4, or 8 hrs after return of spontaneous circulation compared to 9% in normothermic controls (*p < .01 vs. normothermia). Furthermore, surviving neuron counts were greater when therapeutic hypothermia was maintained for 48 hrs compared to 24 hrs (68% ± 15%* vs. 42% ± 22%, *p < .0001).
  
  
  CONCLUSIONS
  In this study, post-cardiac-arrest therapeutic hypothermia resulted in comparable improvement of survival and survival with good neurologic function when initiated within 4 hrs after return of spontaneous circulation. However, histologic assessment of neuronal survival revealed a potentially broader therapeutic window and greater neuroprotection when therapeutic hypothermia was maintained for 48 vs. 24 hrs.
authors: Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors: Dongfang
authors: D
authors: Che
authors: Luchuan
authors: L
authors: Li
authors: Catherine M
authors: CM
authors: Kopil
authors: Ziyue
authors: Z
authors: Liu
authors: Wensheng
authors: W
authors: Guo
authors: Robert W
authors: RW
authors: Neumar
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