Abstract

Objective: Cardiac arrest (CA) survivors progress through electroencephalographic (EEG) burst-suppression prior to arousal. Orexin-A, an excitatory neuropeptide, elicits arousal EEG patterns during anesthetic-induced burst-suppression. We hypothesized that intraventricular injection of orexin-A would improve arousal and burst-suppression after CA in rats. Methods: Eighteen Wistar rats were subjected to 7-minute asphyxial CA and resuscitation by external cardiac massage. Rats were divided into treatment (n=9) and control (n=9) groups. Twenty minutes after resuscitation, the treatment group received 0.1 mL of 1nM orexin-A intraven-tricularly, while controls received saline. EEG was continuously monitored and quantified using Information Quantity (IQ), a measure of entropy validated for detection of burst-suppression and arousal patterns. IQ was normalized to baseline prior to CA (range 0 –1.0). Arousal was quantified using the neurological deficit scale (NDS). Stereologic microscopy was used to determine the ischemic neuronal fraction of hippocampus CA1 and cortex. Results: Baseline and post-resuscitation characteristics were similar between the 2 groups. Burst frequency by visual inspection was similar after administration of orexin-A or saline. Rats in the orexin-A group demonstrated higher IQ values (mean±SD) compared to controls beginning 10 minutes after drug injection (0.564±0.098 vs. 0.429±0.116, p=0.024). IQ values remained significantly higher in the orexin-A group for the first 60 minutes after drug injection and subsequently converged. The NDS score (mean±SD) at 4 hours was higher in the orexin-A group compared to controls (57.3±5.8 vs. 40.7±5.9, p<0.02), but scores were similar at 72 hours. The ischemic neuronal fraction was similar between groups in cortex (p=0.54) and hippocampus CA1 (p=0.14). Conclusions: In rats resuscitated from CA, orexin-A hastened improvement of EEG entropy and arousal measures without increasing ischemic neuronal injury. The role of orexin-A in hastening arousal after CA deserves further investigation.

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