Background: Noble gases such as xenon, helium and argon (Ar) have been reported to have cytoprotective effects. In particular, Ar is non-anesthetic, the third most abundant gas in the atmosphere, and is considered to have the advantages of high safety and low cost. Although the inhibitory effects of Ar on ischemia-reperfusion injury (IRI) have been reported at the cellular and small animal models, there are limited reports in large animal models. We previously demonstrated that perioperative Ar inhalation suppressed IRI via anti-apoptotic and antioxidant effects using the porcine warm IRI model. However, the effectiveness of Ar inhalation in the kidney was inconclusive in previous studies in the published papers performed by other groups. Therefore, in this study, we evaluated the applicability of Ar inhalation to kidney transplantation using an experimental transplantation model using MHC-inbred CLAWN miniature swine.
Methods: MHC-matched donor-recipient combinations were selected for this study. Graft kidneys were preserved in UW solution for 5 hours, then transplanted into the recipient, and the contralateral kidney was removed. For 360 minutes from the start of surgery to 2 hours after reperfusion of the transplanted kidney, the Ar inhalation group (n=2) received 30% oxygen mixed with 70% Ar, while the control group (n=3) inhaled oxygen only. The effect of Ar inhalation was evaluated by the presence of side effects, renal function (serum creatinine: Cr) over 14 days, and renal biopsy at 1 hour after reperfusion and at postoperative day (POD)14.
Results: No obvious side effects such as changes in blood pressure during surgery or prolonged anesthesia awakening due to Ar inhalation were observed. After 5 hours of cold preservation and subsequent transplantation, one recipient in the control group showed delayed graft function (DGF), peaking at POD8 (Cr 6.7 mg/dl). The remaining two animals showed elevated Cr, peaking on POD2, with a mean Cr of 2.67 mg/dl. Similarly, two recipients in the Ar inhalation group also showed an increase in Cr with a peak on POD2, with a mean of 2.98 mg/dl. Except for one case of DGF in the control group, no significant differences in biopsy findings or serum cytokine analysis were observed between the groups.
Conclusion: In this study in miniature swine, there was no clear protective effect of perioperative Ar inhalation on the transplanted kidney. It is possible that the effect of Ar was not demonstrated because a model with mild renal dysfunction was used and because, in contrast to lung experiments, the damage was mainly caused by cold preservation. In future analyses, we aim to elucidate the reasons for the lack of efficacy of argon in this model by performing detailed evaluations with serum and tissue samples.