Attenuation of mitochondrial dysfunction in a ventricular fibrillation swine model of cardiac arrest treated with carbon monoxide.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) affects over 360,000 adults in the United States each year with a 50-80% mortality. Despite aggressive supportive care and use of targeted temperature management, half of adults do not live to hospital discharge and nearly one-third of survivors have significant neurologic injury. Development of neuroprotective therapeutics is critical to improving outcomes. One promising readily available agent that has shown benefit is carbon monoxide (CO). METHODS: We utilize a swine model of ventricular fibrillation (VF) arrest to assess the therapeutic effect of CO on cellular measures. All animals underwent VF arrest followed by cardiopulmonary resuscitation until achievement of return of spontaneous circulation (ROSC) or the 20 min mark. One hour following ROSC, animals were randomized to the Cardiac Arrest group (VF alone) versus the CO group (VF treated with CO). Animals in the CO group were administered low dose CO of 200 ppm for two hours. At three hours post-ROSC period, all animals were euthanized for tissue and blood collection for mitochondrial respiration (cortical and hippocampal tissue) and the downstream biomolecular analysis. RESULTS: The primary findings were an overall improvement in mitochondrial respiration and ATP concentrations in the brain from animals in the CO group. In addition, we also report the use of cell-free DNA as a biomarker to localize the site of tissue injury and our non-invasive optical monitoring device to assess cerebral metabolism. CONCLUSIONS: CO may be a potential therapeutic to attenuate cellular injury in post-arrest.