Ko Tiffany S, Greenwood John C, Morgan Ryan W, Abella Benjamin S, Shofer Frances S, Mason McKenna, Weintraub Devora, Bungatavula Devesh, Lewis Alistair, Ranieri Nicolina R, Yodh Arjun G, Baker Wesley B, Forti Rodrigo M, Kao Shih-Han, Shin Samuel S, Kilbaugh Todd J, Jang David H
Resuscitation Science Center, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Resuscitation. 2025 Aug;213:110647. doi: 10.1016/j.resuscitation.2025.110647. Epub 2025 May 16.
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).
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.
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.
CO may be a potential therapeutic to attenuate cellular injury in post-arrest.
在美国，院外心脏骤停（OHCA）每年影响超过36万成年人，死亡率为50%-80%。尽管采取了积极的支持性治疗并使用了目标温度管理，但仍有一半的成年人未能存活至出院，近三分之一的幸存者有严重的神经损伤。开发神经保护疗法对于改善预后至关重要。一种已显示出益处且容易获得的有前景的药物是一氧化碳（CO）。
我们利用猪室颤（VF）骤停模型来评估CO对细胞指标的治疗效果。所有动物均经历VF骤停，随后进行心肺复苏，直至实现自主循环恢复（ROSC）或达到20分钟标记。ROSC后1小时，将动物随机分为心脏骤停组（仅VF）和CO组（用CO治疗的VF）。CO组的动物接受200 ppm的低剂量CO治疗两小时。在ROSC后3小时，对所有动物实施安乐死，以采集组织和血液用于线粒体呼吸（皮质和海马组织）及下游生物分子分析。
主要发现是CO组动物大脑中的线粒体呼吸和ATP浓度总体有所改善。此外，我们还报告了使用游离DNA作为生物标志物来定位组织损伤部位，以及使用我们的非侵入性光学监测设备来评估脑代谢。
CO可能是减轻骤停后细胞损伤的一种潜在治疗方法。
