The Efficacy of Noble Gases in the Attenuation of Ischemia Reperfusion Injury: A Systematic Review and Meta-Analyses

Objective: Noble gases have been attributed to organ protective effects in ischemia reperfusion injury in a variety of medical conditions, including cerebral and cardiac ischemia, acute kidney injury, and transplantation. The aim of this study was to appraise the available evidence by systematically reviewing the literature and performing meta-analyses. Data Sources: PubMed, EMBASE, and the Cochrane Library. Study Selection: Inclusion criteria specified any articles on noble gases and either ischemia reperfusion injury or transplantation. In vitro studies, publications without full text, review articles, and letters were excluded. Data Extraction: Information on noble gas, organ, species, model, length of ischemia, conditioning and noble gas dose, duration of administration of the gas, endpoints, and effects was extracted from 79 eligible articles. Study quality was evaluated using the Jadad scale. Effect sizes were extracted from the articles or retrieved from the authors to allow meta-analyses using the random-effects approach. Data Synthesis: Argon has been investigated in cerebral, myocardial, and renal ischemia reperfusion injury; helium and xenon have additionally been tested in hepatic ischemia reperfusion injury, whereas neon was only explored in myocardial ischemia reperfusion injury. The majority of studies show a protective effect of these noble gases on ischemia reperfusion injury across a broad range of experimental conditions, organs, and species. Overall study quality was low. Meta-analysis for argon was only possible in cerebral ischemia reperfusion injury and did not show neuroprotective effects. Helium proved neuroprotective in rodents and cardioprotective in rabbits, and there were too few data on renal ischemia reperfusion injury. Xenon had the most consistent effects, being neuroprotective in rodents, cardioprotective in rodents and pigs, and renoprotective in rodents. Conclusions: Helium and xenon show organ protective effects mostly in small animal ischemia reperfusion injury models. Additional information on timing, dosing, and comparative efficacy of the different noble gases, as well as confirmation in large animal models, is needed before designing clinical trials.