CO-releasing molecule-3 (CORM-3) is a transitional metal carbonyl that liberates carbon monoxide under appropriate conditions. Carbon monoxide exerts effects on intracellular apoptotic and inflammatory pathways, which suggest a role in reducing the effects of renal ischemia/reperfusion (I/R) injury. This study investigated the effects of CORM-3 administered at the time of reperfusion in a model of controlled nonheartbeating donor kidneys.Methods.
Porcine kidneys (n=4) were subjected to 10 min warm ischemia and 18 hr cold storage (CS) and then treated as follows: CORM-3 (50, 100, 200, and 400 μM doses), iCORM-3 (inactive carbon monoxide-releasing molecule, 50 μM), and control (no further intervention). Renal hemodynamics and function were then measured during 3-hr reperfusion with autologous blood using an isolated organ-perfusion system.Results.
CORM-3 at a concentration of 50 μM improved renal blood flow (RBF) compared with the iCORM and control groups (area under the curve 774±19 vs. 448±88 vs. 325±70, respectively, P=0.002). CO-releasing molecule-3 at a concentration of 50 μM also improved renal function during reperfusion with a greater area under the curve for creatinine clearance (CORM-3: 14±6 vs. iCORM: 3.3±0.1 vs. control: 2.2±2 mL/min, P=0.006) and higher urine output (CORM-3: 793±212 vs. iCORM: 368±72 vs. control: 302±211 mL, P=0.01). CO-releasing molecule-3 at a concentration of 100 μM exerted similar effects. Treatment with CORM-3 at higher doses (200 and 400 μM) led to poor renal hemodynamics and function after reperfusion.Conclusion.
Low-dose CORM-3 significantly ameliorates the effects of ischemia/reperfusion in a porcine model of controlled nonheartbeating donor kidney transplantation.