Mitochondrial Transplantation Reduces Injury and Improves Liver Function in a Porcine Model of Hemi-Hepatic Ischemia/reperfusion

Objective: To assess mitochondrial transplantation (MitoTx) via portal vein infusion to reduce liver ischemia-reperfusion injury (I/R) in a survival porcine model. Summary Background Data: MitoTx has been shown to alleviate I/R injury in various organs. Methods: Male Yorkshire pigs (38±1 kg) were subjected to 2 hours of ischemia in the left hemi-liver (left portal-triad clamping), and at the beginning of reperfusion (marked as t=0h), animals received a 1-hour infusion of autologous mitochondria (MT, 6.71×109/kg) or saline (controls) via the portal vein. Liver tissue oxygen saturation (sO 2 ) was assessed by photoacoustic imaging. Results: Twelve pigs (6 MitoTx vs. 6 controls) underwent 2-hour left hemi-liver I/R. All pigs recovered and were ambulatory at t=6h. MitoTx reduced peak AST levels at t=2h compared to controls (299.83±46.62 vs. 878.83±255.09 UI/L; P =0.049). At t=24h, MitoTx pigs had lowered necrosis area percentage (8.01±4.12 vs. 23.40±7.33%; P =0.08) in left livers– all right lobes had 0% necrotic area. MitoTx pigs had shorter prothrombin time, plateauing around t=8h (12.9±0.3 vs. 14.1±0.1s; P =0.003), faster lactate clearance (<2 mmol/L) from the blood (HR: 1.3, [1.1, 1.7]; P =0.003) and from the bile (HR: 1.4, [1.1, 1.7]; P =0.009) compared to controls. At t=6h, MitoTx pigs had decreased IL-6 (304±71 vs. 686±87 pg/mL; P =0.007). Photoacoustic imaging showed that MitoTx pigs had a smaller variation of sO 2 from baseline in left livers compared to controls (at t=30min; -3.05±2.72 vs. -15.19±2.92%; P =0.016). Conclusion: MitoTx reduces injury and improves liver function after prolonged liver I/R, showing promise for liver transplantation.