1400W reduces ischemia reperfusion injury in an ex-vivo porcine model of the donation after circulatory death kidney donor

摘要

AIM: To investigate the effects of 1400W-a selective inducible nitric oxide synthase(iN OS) inhibitor in a model of donation after circulatory death(DCD) kidneys. METHODS: Porcine kidneys were retrieved after 25 min warm ischemia. They were then stored on ice for 18 h before being reperfused ex vivo with oxygenated autologous blood on an isolated organ perfusion system. The selective i NOS inhibitor 1400W(10 mg/kg) was administered before reperfusion(n = 6) vs control group(n = 7). Creatinine(1000 μmol/L) was added to the system, renal and tubular cell function and the level of ischemia reperfusion injury were assessed over 3 h of reperfusion using plasma, urine and tissue samples. RESULTS: Kidneys treated with 1400 W had a higher level of creatinine clearance(CrC l) [area under the curve(AUC) CrC l: 2.37 ± 0.97 mL /min per 100 g vs 0.96 ± 0.32 mL /min per 100 g, P = 0.004] and urine output [Total: 320 ± 96 mL vs 156 ± 82 mL, P = 0.008]. There was no significant difference in levels of fractional excretion of sodium(AUC, Fr ex Na+: Control, 186.3% ± 81.7%.h vs 1400 W, 153.4% ± 12.1%.h, P = 0.429). Levels of total protein creatinine ratio were significantly lower in the 1400 W group after 1 h of reperfusion(1h Pr/Cr: 1400 W 9068 ± 6910 mg/L/mmol/L vs Control 21586 ± 5464 mg/L/mmol/L, P = 0.026). Levels of 8-isoprostane were significantly lower in the 1400 W group [8-iso/creatinine ratio: Control 239 ± 136 pg/L/mmol/L vs 1400 W 139 ± 47 pg/L/mmol/L, P = 0.041].CONCLUSION: This study demonstrated that 1400 W reduced ischaemia reperfusion injury in this porcine kidney model of DCD donor. Kidneys had improved renal function and reduced oxidative stress.