Dataset Information

Effect of the KCa3.1 blocker, senicapoc, on cerebral edema and cardiovascular function after cardiac arrest - A randomized experimental rat study.

ABSTRACT:

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.

SUBMITTER: Hansen FB

PROVIDER: S-EPMC8244250 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AimPrevious studies have examined the association between quantitative head computed tomography (CT) measures of cerebral edema and patient outcomes reporting that a calculated gray matter to white matter attenuation ratio (GWR) of <1.2 indicates a near 100% non-survivable injury post-cardiac arrest. The objective of the current study was to validate whether a GWR <1.2 reliably indicates poor survival post-cardiac arrest. We also sought to determine the inter-rater variability among reviewers, and examine the utility of a novel GWR measurement to facilitate easier practical use.MethodsWe performed a retrospective analysis of post-cardiac arrest patients admitted to a single center from 2008 to 2012. Inclusion criteria were age ≥18 years, non-traumatic arrest, and available CT imaging within 24h after ROSC. Three independent physician reviewers from different specialties measured CT attenuation of pre-specified gray and white matter areas for GWR calculations.ResultsOut of 171 consecutive patients, 90 met the study inclusion criteria. Thirteen patients were excluded for technical reasons and/or significant additional pathology, leaving 77 head CT scans for evaluation. Median age was 66 years and 64% were male. In-hospital mortality was 65% and 70% of patients received therapeutic hypothermia. For the validation measurement, the intra-class correlation coefficient was 0.70. In our dataset, a GWR below 1.2 did not accurately predict mortality or poor neurological outcome (sensitivity 0.56-0.62 and specificity 0.63-0.81). A score below 1.1 predicted a near 100% mortality but was not a sensitive metric (sensitivity 0.14-0.20 and specificity 0.96-1.00). Similar results were found for the exploratory model.ConclusionA GWR <1.2 on CT imaging within 24h after cardiac arrest was moderately specific for poor neurologic outcome and mortality. Based on our data, a threshold GWR <1.1 may be a safer cut-off to identify patients with low chance of survival and good neurological outcome. Intra-class correlation among reviewers was moderately good.