Carbon monoxide protects against ischemia-reperfusion injury in an experimental model of controlled nonheartbeating donor kidney.
BACKGROUND
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 microM doses), iCORM-3 (inactive carbon monoxide-releasing molecule, 50 microM), 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 microM 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 microM 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 microM exerted similar effects. Treatment with CORM-3 at higher doses (200 and 400 microM) led to poor renal hemodynamics and function after reperfusion.


CONCLUSIONS
Low-dose CORM-3 significantly ameliorates the effects of ischemia/reperfusion in a porcine model of controlled nonheartbeating donor kidney transplantation.
Bagul
Atul
A
Department of Transplant Surgery, University Hospitals of Leicester, Leicester, United Kingdom.
Hosgood
Sarah A
SA
Kaushik
Monika
M
Nicholson
Michael L
ML
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002102:Cadaver; D003404:Creatinine / Q000378:metabolism; D007668:Kidney / Q000187:drug effects; D023421:Models, Animal; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D012079:Renal Circulation / Q000187:drug effects*; D015424:Reperfusion / Q000379:methods; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine; D014019:Tissue Donors
D009942:Organometallic Compounds; C476530:tricarbonylchloro(glycinato)ruthenium(II); D003404:Creatinine