A randomized trial of the effects of the noble gases helium and argon on neuroprotection in a rodent cardiac arrest model

Patrick Zuercher, Dirk Springe, Denis Grandgirard, Stephen L. Leib, Marius Grossholz, Stephan Jakob, Jukka Takala, Matthias Haenggi

The noble gas xenon is considered as a neuroprotective agent, but availability of the gas is limited. Studies on neuroprotection with the abundant noble gases helium and argon demonstrated mixed results, and data regarding neuroprotection after cardiac arrest are scant. We tested the hypothesis that administration of 50 % helium or 50 % argon for 24 h after resuscitation from cardiac arrest improves clinical and histological outcome in our 8 min rat cardiac arrest model. Forty animals had cardiac arrest induced with intravenous potassium/esmolol and were randomized to post-resuscitation ventilation with either helium/oxygen, argon/oxygen or air/oxygen for 24 h. Eight additional animals without cardiac arrest served as reference, these animals were not randomized and not included into the statistical analysis. Primary outcome was assessment of neuronal damage in histology of the region I of hippocampus proper (CA1) from those animals surviving until day 5. Secondary outcome was evaluation of neurobehavior by daily testing of a Neurodeficit Score (NDS), the Tape Removal Test (TRT), a simple vertical pole test (VPT) and the Open Field Test (OFT). Because of the non-parametric distribution of the data, the histological assessments were compared with the Kruskal-Wallis test. Treatment effect in repeated measured assessments was estimated with a linear regression with clustered robust standard errors (SE), where normality is less important. Twenty-nine out of 40 rats survived until day 5 with significant initial deficits in neurobehavioral, but rapid improvement within all groups randomized to cardiac arrest. There were no statistical significant differences between groups neither in the histological nor in neurobehavioral assessment. The replacement of air with either helium or argon in a 50:50 air/oxygen mixture for 24 h did not improve histological or clinical outcome in rats subjected to 8 min of cardiac arrest.