title: Combined intra- and post-cardiac arrest hypothermic-targeted temperature management in a rat model of asphyxial cardiac arrest improves survival and neurologic outcome compared to either strategy alone.
abstract: Post-cardiac arrest hypothermic-targeted temperature management (HTTM) improves outcomes in preclinical cardiac arrest studies. However, inadequate understanding of the mechanisms and therapeutic windows remains a barrier to optimization. We tested the hypothesis that combined intra- and post-cardiac arrest HTTM provides a synergistic outcome benefit compared to either strategy alone.
  
  
  
  Rats subjected to 8-min asphyxial cardiac arrest were block randomized to 4 treatment groups (n=12/group): NTTM) normothermic-targeted temperature management; 1-24 HTTM) HTTM initiated 1h post-ROSC and maintained for 24h; Intra-1 HTTM) HTTM initiated at CPR onset and maintained for 1h; and Intra-24 HTTM) HTTM initiated at CPR onset and maintained for 24h. HTTM was induced by nasopharyngeal cooling and maintained using an automated temperature regulation system. Target temperature range was 36.5-37.5°C for NTTM and 32.0-34.0°C for HTTM. Post-arrest neurologic function score (NFS) was measured daily, and rats surviving 72h were euthanized for histological analysis of neurodegeneration.
  
  
  
  Target brain temperature was achieved 7.8±3.3min after initiating intra-arrest cooling. The survival rate was 42%, 50%, 50%, and 92% in the NTTM, 1-24 HTTM, Intra-1 HTTM, and Intra-24 HTTM groups, respectively (p<0.05, Intra-24 group vs. all other groups). The rate of survival with good neurologic function (NFS≥450) was 33% in the Intra-24 HTTM group vs. 0% in all other groups (mid p<0.05). Hippocampal CA1 sector neurodegeneration was significantly reduced in the Intra-24 HTTM group compared to all other groups (p<0.05).
  
  
  
  Combined intra- and post-cardiac arrest HTTM has greater outcome benefits than either strategy alone.
authors: Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, United States; Department of Emergency Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; Department of Emergency Medicine, Gyeongsang National University Hospital, Republic of Korea.
authors: Taeyun
authors: T
authors: Kim
authors: Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, United States.
authors: Michael G
authors: MG
authors: Paine
authors: Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, United States; Michigan Center for Integrative Research in Critical Care (MCIRCC), University of Michigan, Ann Arbor, MI, United States.
authors: He
authors: H
authors: Meng
authors: Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, United States; Michigan Center for Integrative Research in Critical Care (MCIRCC), University of Michigan, Ann Arbor, MI, United States.
authors: Ren
authors: R
authors: Xiaodan
authors: Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, United States; Michigan Center for Integrative Research in Critical Care (MCIRCC), University of Michigan, Ann Arbor, MI, United States.
authors: Jacob
authors: J
authors: Cohen
authors: Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, United States; Michigan Center for Integrative Research in Critical Care (MCIRCC), University of Michigan, Ann Arbor, MI, United States.
authors: Tulasi
authors: T
authors: Jinka
authors: Department of Biostatistics, University of Michigan, Ann Arbor, MI, United States.
authors: Huiyong
authors: H
authors: Zheng
authors: Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, United States; Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
authors: James A
authors: JA
authors: Cranford
authors: Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, United States; Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, United States; Michigan Center for Integrative Research in Critical Care (MCIRCC), University of Michigan, Ann Arbor, MI, United States. Electronic address: neumar@umich.edu.
authors: Robert W
authors: RW
authors: Neumar
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000150:complications*; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D007036:Hypothermia, Induced / Q000379:methods*; D009460:Neurologic Examination / Q000379:methods; D051381:Rats; D020127:Recovery of Function; D013997:Time Factors; D016896:Treatment Outcome
keywords: Cardiac arrest; Post-cardiac arrest; Targeted temperature management; Therapeutic hypothermia