Post-cardiac arrest therapeutic hypothermia (TH) improves outcomes in comatose cardiac arrest survivors. This study tests the hypothesis that the efficacy of post-cardiac arrest TH is dependent on the onset and duration of therapy.
Prospective randomized laboratory investigation
University research laboratory
268 male Long Evans rats
Post-cardiac arrest therapeutic hypothermia
Measurements and Main Results
Adult male Long Evans rats that achieved return of spontaneous circulation (ROSC) after a 10-min asphyxial cardiac arrest were block randomized to normothermia (37±1°C) or TH (33±1°C) initiated 0, 1, 4, or 8 hrs after ROSC and maintained for 24 or 48 hrs. TH initiated 0, 1, 4, and 8 hours after ROSC 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<0.05 vs. normothermia). These outcomes were not different when TH was maintained for 24 vs. 48 hours. In contrast, hippocampal CA1 pyramidal neuron counts were 53±27%*, 53±19%*, 51±24%*, and 65±16%* of normal respectively when TH initiated 0, 1, 4, or 8 hrs after ROSC compared to 9% in normothermic controls (*p<0.01 vs. normothermia). Furthermore, surviving neuron counts were greater when TH was maintained for 48 hrs compared to 24 hrs (68%±15%* vs. 42%±22%, *p<0.0001)
In this study, post-cardiac arrest TH resulted in comparable improvement of survival and survival with good neurologic function when initiated within 4-hours after ROSC. However, histological assessment of neuronal survival revealed a potentially broader therapeutic window and greater neuroprotection when TH was maintained for 48 vs. 24 hours.