Argon Attenuates Multiorgan Failure in Relation with HMGB1 Inhibition

Argon inhalation attenuates multiorgan failure (MOF) after experimental ischemic injury. We hypothesized that this protection could involve decreased High Mobility Group Box 1 (HMGB1) systemic release. We investigated this issue in an animal model of MOF induced by aortic cross-clamping. Anesthetized rabbits were submitted to supra-coeliac aortic cross-clamping for 30 min, followed by 300 min of reperfusion. They were randomly divided into three groups (n = 7/group). The Control group inhaled nitrogen (70%) and oxygen (30%). The Argon group was exposed to a mixture of argon (70%) and oxygen (30%). The last group inhaled nitrogen/oxygen (70/30%) with an administration of the HMGB1 inhibitor glycyrrhizin (4 mg/kg i.v.) 5 min before aortic unclamping. At the end of follow-up, cardiac output was significantly higher in Argon and Glycyrrhizin vs. Control (60 +/- 4 and 49 +/- 4 vs. 33 +/- 8 mL/kg/min, respectively). Metabolic acidosis was attenuated in Argon and Glycyrrhizin vs. Control, along with reduced amount of norepinephrine to reverse arterial hypotension. This was associated with reduced interleukin-6 and HMGB1 plasma concentration in Argon and Glycyrrhizin vs. Control. End-organ damages were also attenuated in the liver and kidney in Argon and Glycyrrhizin vs. Control, respectively. Argon inhalation reduced HMGB1 blood level after experimental aortic cross-clamping and provided similar benefits to direct HMGB1 inhibition.

Automated summary

The inhalation of argon and administration of the HMGB1 inhibitor glycyrrhizin both attenuated multiorgan failure after experimental aortic cross-clamping, leading to improved cardiac output, ameliorated metabolic acidosis, reduced norepinephrine requirement, decreased interleukin-6 and HMGB1 plasma concentration, as well as alleviated end-organ damages in the liver and kidney. Argon inhalation was able to reduce HMGB1 blood levels after aortic cross-clamping and provided similar benefits to direct HMGB1 inhibition.