Hydrogen gas with extracorporeal cardiopulmonary resuscitation improves survival after prolonged cardiac arrest in rats

Journal of Translational Medicine

Daniel M. Rolston¹  Koichiro Homma²  Junichi Sasaki²  Shuhei Eguchi³  Tadashi Ariyoshi³  Kentaro Oka³  Asami Matsumoto³  Motomichi Takahashi³  Yusuke Endo⁴  Tomoaki Aoki⁴  Tai Yin⁴  Lance B. Becker⁴  Koichiro Shinozaki⁴  Junhwan Kim⁴  Muhammad Shoaib⁴  Kei Hayashida⁴  Rishabh C. Choudhary⁴  Ryosuke Takegawa⁴  Santiago J. Miyara⁴  Mitsuaki Nishikimi⁴  Ernesto P. Molmenti⁵ 

[1] Department of Emergency Medicine, North Shore University Hospital, Northwell Health;Department of Emergency and Critical Care Medicine, Keio University School of Medicine;R&D Division, Miyarisan Pharmaceutical Co., Ltd.;The Feinstein Institutes for Medical Research, Northwell Health System;Zucker School of Medicine at Hofstra/Northwell;

关键词: Heart arrest;    Extracorporeal cardiopulmonary resuscitation;    Extracorporeal membrane oxygenation;    Hydrogen;    Ischemia reperfusion injury;   

DOI  :  10.1186/s12967-021-03129-1

来源: DOAJ

【 摘 要 】

Abstract Background Despite the benefits of extracorporeal cardiopulmonary resuscitation (ECPR) in cohorts of selected patients with cardiac arrest (CA), extracorporeal membrane oxygenation (ECMO) includes an artificial oxygenation membrane and circuits that contact the circulating blood and induce excessive oxidative stress and inflammatory responses, resulting in coagulopathy and endothelial cell damage. There is currently no pharmacological treatment that has been proven to improve outcomes after CA/ECPR. We aimed to test the hypothesis that administration of hydrogen gas (H2) combined with ECPR could improve outcomes after CA/ECPR in rats. Methods Rats were subjected to 20 min of asphyxial CA and were resuscitated by ECPR. Mechanical ventilation (MV) was initiated at the beginning of ECPR. Animals were randomly assigned to the placebo or H2 gas treatment groups. The supplement gas was administered with O2 through the ECMO membrane and MV. Survival time, electroencephalography (EEG), brain functional status, and brain tissue oxygenation were measured. Changes in the plasma levels of syndecan-1 (a marker of endothelial damage), multiple cytokines, chemokines, and metabolites were also evaluated. Results The survival rate at 4 h was 77.8% (7 out of 9) in the H2 group and 22.2% (2 out of 9) in the placebo group. The Kaplan–Meier analysis showed that H2 significantly improved the 4 h-survival endpoint (log-rank P = 0.025 vs. placebo). All animals treated with H2 regained EEG activity, whereas no recovery was observed in animals treated with placebo. H2 therapy markedly improved intra-resuscitation brain tissue oxygenation and prevented an increase in central venous pressure after ECPR. H2 attenuated an increase in syndecan-1 levels and enhanced an increase in interleukin-10, vascular endothelial growth factor, and leptin levels after ECPR. Metabolomics analysis identified significant changes at 2 h after CA/ECPR between the two groups, particularly in d-glutamine and d-glutamate metabolism. Conclusions H2 therapy improved mortality in highly lethal CA rats rescued by ECPR and helped recover brain electrical activity. The underlying mechanism might be linked to protective effects against endothelial damage. Further studies are warranted to elucidate the mechanisms responsible for the beneficial effects of H2 on ischemia–reperfusion injury in critically ill patients who require ECMO support.

【 授权许可】

Unknown