METHANE ADMINISTRATION DURING OXYGENATION MITIGATES ACUTE KIDNEY INJURY IN A PIG MODEL OF 24-H VENO-VENOUS EXTRACORPOREAL MEMBRANE OXYGENATION.

Abstract

Abstract: Background: Severe respiratory failure often requires veno-venous extracorporeal membrane oxygenation (v-v ECMO) treatment, a procedure frequently associated with acute kidney injury (AKI). Preclinical studies have demonstrated the anti-inflammatory properties of inhaled methane (CH 4 ). This experimental protocol aimed to investigate whether CH 4 gas administration could mitigate the development of AKI in a clinically relevant large animal model of v-v ECMO. Methods: Anesthetized miniature pigs were divided into three groups (n = 6 each). Following cannulation of the right femoral and internal jugular veins, v-v ECMO was initiated and maintained for 24 h, followed by a 6-h post-ECMO observation. The control group underwent cannulation without ECMO, while the v-v ECMO+CH 4 group received a 2% CH 4 -air mixture via the oxygenator. Urine output was recorded, and kidney injury was assessed using plasma and urine neutrophil gelatinase-associated lipocalin levels. Inflammatory activation was evaluated through plasma interleukin-1β (IL-1β) and interleukin-8 (IL-8) levels. Kidney tissue samples were analyzed for histopathological changes, xanthine oxidoreductase and myeloperoxidase activities, and nitrite/nitrate levels. Results: The CH 4 -treated group exhibited significantly higher post-ECMO renal arterial flow (244.7 ± 70 vs. 96.3 ± 21 mL/min) and increased average urine output (5.75 ± 1.6 vs. 3.25 ± 0.4 mL/h/kg) compared to the v-v ECMO group. CH 4 administration reduced urine and plasma neutrophil gelatinase-associated lipocalin levels and demonstrated lower histological damage scores (0.8 ± 0.3 vs. 3.3 ± 0.8). Furthermore, CH 4 treatment decreased xanthine oxidoreductase and myeloperoxidase activities and reduced inflammatory mediators, including IL-1β, IL-8, and nitrite/nitrate. Conclusion: CH 4 admixture significantly mitigates inflammatory activation and renal injury associated with v-v ECMO. These findings suggest that CH 4 may serve as an effective adjunctive means to reduce renal complications of v-v ECMO therapy.