Intraventricular orexin-A improves arousal and early EEG entropy in rats after cardiac arrest

Abstract

The recovery of arousal after cardiac arrest (CA) is associated with evolution from electroencephalographic (EEG) burst-suppression to continuous activity. Orexin-A elicits arousal EEG during anesthetic burst-suppression. We hypothesized that orexin-A would improve arousal and EEG entropy after CA. Eighteen Wistar rats were subjected to 7-minute asphyxial CA and resuscitation. Rats were divided into treatment ( n = 9) and control ( n = 9) groups. Twenty minutes after resuscitation, the treatment group received 0.1 mL of 1 nM orexin-A intraventricularly, while controls received saline. EEG was quantified using Information Quantity (IQ), a measure of entropy validated for detection of burst-suppression and arousal patterns. IQ values range from 0 to 1.0. Arousal was quantified using the neurological deficit scale (NDS). The ischemic neuronal fraction of hippocampus CA1 and cortex was histologically determined. Baseline and post-resuscitation characteristics were similar between the groups. The NDS score (mean ± SD) at 4 h 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 h. Burst frequency was similar in both groups but the orexin-A group demonstrated higher IQ values compared to controls beginning within 10 min. IQ values remained significantly higher in the orexin-A group for the first 120 min ( p = 0.008) and subsequently converged. The ischemic neuronal fraction was similar between groups in cortex ( p = 0.54) and hippocampus CA1 ( p = 0.14). In rats resuscitated from CA, orexin-A transiently increased arousal and EEG entropy without worsening ischemic neuronal injury. The role of orexin-A in recovery of arousal after CA deserves further investigation.