| Summary: | Aim: Formation of cerebral edema and cardiovascular dysfunction may worsen brain injury following cardiac arrest. We hypothesized that administration of the intermediate calcium-activated potassium (KCa3.1) channel blocker, senicapoc, would reduce cerebral edema and augment mean arterial pressure in the early post-resuscitation period. Method: Male Sprague-Dawley rats, aged 11–15 weeks, were utilized in the study. Rats were exposed to 8 min of asphyxial cardiac arrest. Shortly after resuscitation, rats were randomized to receive either vehicle or senicapoc (10 mg/kg) intravenously. The primary outcome was cerebral wet to dry weight ratio 4 h after resuscitation. Secondary outcomes included mean arterial pressure, cardiac output, norepinephrine dose, inflammatory cytokines and neuron specific enolase levels. Additionally, a sub-study was conducted to validate intravenous administration of senicapoc. Results: The sub-study revealed that senicapoc-treated rats maintained a significantly higher mean arterial pressure during administration of SKA-31 (a KCa3.1 channel opener).The plasma concentration of senicapoc was 1060 ± 303 ng/ml 4 h after administration. Senicapoc did not reduce cerebral edema or augment mean arterial pressure 4 h after resuscitation. Likewise, cardiac function and norepinephrine dose did not vary between groups. Inflammatory cytokines and neuron specific enolase levels increased in both groups after resuscitation with no difference between groups. Senicapoc enhanced the PaO2/FiO2 ratio significantly 4 h after resuscitation. Conclusion: Senicapoc was successfully administered intravenously after resuscitation, but did not reduce cerebral edema or increase mean arterial pressure in the early post-resuscitation period.
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