Preserved heart rate variability during therapeutic hypothermia correlated to 96 hrs neurological outcomes and survival in a pig model of cardiac arrest

OBJECTIVE: Therapeutic hypothermia initiated with cardiopulmonary resuscitation improves neurologic outcomes and survival after prolonged cardiac arrest. However, the potential mechanism by which hypothermia improves neurologic outcomes remains unclear. In the current study, we investigated the effect of rapid head cooling on 96-hr neurologic outcomes and survival by heart rate variability analysis in a pig model of prolonged cardiac arrest. DESIGN: Prospective randomized controlled animal study. SETTING: University-affiliated research laboratory. SUBJECTS: Yorkshire-X domestic pigs (Sus scrofa). INTERVENTIONS: A protocol of 10 mins of untreated ventricular fibrillation followed by 5 mins of cardiopulmonary resuscitation in a pig model of cardiac arrest was used in this study. Sixteen male domestic pigs weighing between 39 and 45 kg were randomized into two groups, hypothermia (n = 8) and control (n = 8). For the hypothermia group, intranasal-induced head cooling was initiated with cardiopulmonary resuscitation and persisted for 4 hrs after resuscitation. For the control group, cardiopulmonary resuscitation was started with normothermia. MEASUREMENTS AND MAIN RESULTS: Time and frequency domain heart rate variability was calculated in 5-min sections of electrocardiographic recordings at baseline and 4 hrs after resuscitation. Neurologic outcomes were evaluated every 24 hrs during the 96-hr postresuscitation observation period. No differences in the baseline measurement and resuscitation outcome were observed between the groups. However, the 96-hr cerebral performance categories of the hypothermic group were significantly lower than control (1.0 ± 0.0 vs. 4.0 ± 1.9, p = .003). Four hrs after resuscitation, mean RR interval, heart rate variability triangular index, and normalized very-low-frequency power were restored to baseline in the hypothermia group. Square root of the mean squared differences of successive RR intervals and SD of instantaneous RR intervals were significantly improved in the cooled animals compared with controls. A significant correlation between 4-hr heart rate variability and 96-hr cerebral performance category was observed in this study. CONCLUSION: Selective head cooling maintains a certain level of autonomic nervous system function in this pig model of cardiac arrest. The preserved heart rate variability during postresuscitation hypothermia was associated with favorable 96-hr neurologic recovery and survival.