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

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...

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Autores principales: Tai Yin, Lance B. Becker, Rishabh C. Choudhary, Ryosuke Takegawa, Muhammad Shoaib, Koichiro Shinozaki, Yusuke Endo, Koichiro Homma, Daniel M. Rolston, Shuhei Eguchi, Tadashi Ariyoshi, Asami Matsumoto, Kentaro Oka, Motomichi Takahashi, Tomoaki Aoki, Santiago J. Miyara, Mitsuaki Nishikimi, Junichi Sasaki, Junhwan Kim, Ernesto P. Molmenti, Kei Hayashida
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spelling oai:doaj.org-article:d5cf875a25424634a17f2b652765232c2021-11-21T12:05:05ZHydrogen gas with extracorporeal cardiopulmonary resuscitation improves survival after prolonged cardiac arrest in rats10.1186/s12967-021-03129-11479-5876https://doaj.org/article/d5cf875a25424634a17f2b652765232c2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12967-021-03129-1https://doaj.org/toc/1479-5876Abstract 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.Tai YinLance B. BeckerRishabh C. ChoudharyRyosuke TakegawaMuhammad ShoaibKoichiro ShinozakiYusuke EndoKoichiro HommaDaniel M. RolstonShuhei EguchiTadashi AriyoshiAsami MatsumotoKentaro OkaMotomichi TakahashiTomoaki AokiSantiago J. MiyaraMitsuaki NishikimiJunichi SasakiJunhwan KimErnesto P. MolmentiKei HayashidaBMCarticleHeart arrestExtracorporeal cardiopulmonary resuscitationExtracorporeal membrane oxygenationHydrogenIschemia reperfusion injuryMedicineRENJournal of Translational Medicine, Vol 19, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Heart arrest
Extracorporeal cardiopulmonary resuscitation
Extracorporeal membrane oxygenation
Hydrogen
Ischemia reperfusion injury
Medicine
R
spellingShingle Heart arrest
Extracorporeal cardiopulmonary resuscitation
Extracorporeal membrane oxygenation
Hydrogen
Ischemia reperfusion injury
Medicine
R
Tai Yin
Lance B. Becker
Rishabh C. Choudhary
Ryosuke Takegawa
Muhammad Shoaib
Koichiro Shinozaki
Yusuke Endo
Koichiro Homma
Daniel M. Rolston
Shuhei Eguchi
Tadashi Ariyoshi
Asami Matsumoto
Kentaro Oka
Motomichi Takahashi
Tomoaki Aoki
Santiago J. Miyara
Mitsuaki Nishikimi
Junichi Sasaki
Junhwan Kim
Ernesto P. Molmenti
Kei Hayashida
Hydrogen gas with extracorporeal cardiopulmonary resuscitation improves survival after prolonged cardiac arrest in rats
description 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.
format article
author Tai Yin
Lance B. Becker
Rishabh C. Choudhary
Ryosuke Takegawa
Muhammad Shoaib
Koichiro Shinozaki
Yusuke Endo
Koichiro Homma
Daniel M. Rolston
Shuhei Eguchi
Tadashi Ariyoshi
Asami Matsumoto
Kentaro Oka
Motomichi Takahashi
Tomoaki Aoki
Santiago J. Miyara
Mitsuaki Nishikimi
Junichi Sasaki
Junhwan Kim
Ernesto P. Molmenti
Kei Hayashida
author_facet Tai Yin
Lance B. Becker
Rishabh C. Choudhary
Ryosuke Takegawa
Muhammad Shoaib
Koichiro Shinozaki
Yusuke Endo
Koichiro Homma
Daniel M. Rolston
Shuhei Eguchi
Tadashi Ariyoshi
Asami Matsumoto
Kentaro Oka
Motomichi Takahashi
Tomoaki Aoki
Santiago J. Miyara
Mitsuaki Nishikimi
Junichi Sasaki
Junhwan Kim
Ernesto P. Molmenti
Kei Hayashida
author_sort Tai Yin
title Hydrogen gas with extracorporeal cardiopulmonary resuscitation improves survival after prolonged cardiac arrest in rats
title_short Hydrogen gas with extracorporeal cardiopulmonary resuscitation improves survival after prolonged cardiac arrest in rats
title_full Hydrogen gas with extracorporeal cardiopulmonary resuscitation improves survival after prolonged cardiac arrest in rats
title_fullStr Hydrogen gas with extracorporeal cardiopulmonary resuscitation improves survival after prolonged cardiac arrest in rats
title_full_unstemmed Hydrogen gas with extracorporeal cardiopulmonary resuscitation improves survival after prolonged cardiac arrest in rats
title_sort hydrogen gas with extracorporeal cardiopulmonary resuscitation improves survival after prolonged cardiac arrest in rats
publisher BMC
publishDate 2021
url https://doaj.org/article/d5cf875a25424634a17f2b652765232c
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