title: Ex vivo application of carbon monoxide in UW solution prevents transplant-induced renal ischemia/reperfusion injury in pigs.
abstract: I/R injury is a major deleterious factor of successful kidney transplantation (KTx). Carbon monoxide (CO) is an endogenous gaseous regulatory molecule, and exogenously delivered CO in low concentrations provides potent cytoprotection. This study evaluated efficacies of CO exposure to excised kidney grafts to inhibit I/R injury in the pig KTx model. Porcine kidneys were stored for 48 h in control UW or UW supplemented with CO (CO-UW) and autotransplanted in a 14-day follow-up study. In the control UW group, animal survival was 80% (4/5) with peak serum creatinine levels of 12.0 +/- 5.1 mg/dL. CO-UW showed potent protection, and peak creatinine levels were reduced to 6.9 +/- 1.4 mg/dL with 100% (5/5) survival without any noticeable adverse event or abnormal COHb value. Control grafts at 14 days showed significant tubular damages, focal fibrotic changes and numerous infiltrates. The CO-UW group showed significantly less severe histopathological changes with less TGF-beta and p-Smad3 expression. Grafts in CO-UW also showed significantly lower early mRNA levels for proinflammatory cytokines and less lipid peroxidation. CO in UW provides significant protection against renal I/R injury in the porcine KTx model. Ex vivo exposure of kidney grafts to CO during cold storage may therefore be a safe strategy to reduce I/R injury.
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA.|Department of Surgery and Oncology, Graduate School of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Yoshida
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA.
authors.forename: K S
authors.initials: KS
authors.lastname: Ozaki
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA.|Departments of Surgery and Pathology, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA.
authors.forename: M A
authors.initials: MA
authors.lastname: Nalesnik
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA.
authors.forename: S
authors.initials: S
authors.lastname: Ueki
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA.
authors.forename: M
authors.initials: M
authors.lastname: Castillo-Rama
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA.
authors.forename: G
authors.initials: G
authors.lastname: Faleo
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA.
authors.forename: M
authors.initials: M
authors.lastname: Ezzelarab
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA.
authors.forename: A
authors.initials: A
authors.lastname: Nakao
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA.
authors.forename: B
authors.initials: B
authors.lastname: Ekser
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Echeverri
authors.affiliation: Center for Biologic Imaging, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: M A
authors.initials: MA
authors.lastname: Ross
authors.affiliation: Center for Biologic Imaging, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: D B
authors.initials: DB
authors.lastname: Stolz
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA.
authors.forename: N
authors.initials: N
authors.lastname: Murase
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002248:Carbon Monoxide / Q000008:administration & dosage*; D002263:Carboxyhemoglobin / Q000378:metabolism; D004195:Disease Models, Animal; D006085:Graft Survival; D016030:Kidney Transplantation; D008315:Malondialdehyde / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015427:Reperfusion Injury / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012996:Solutions; D013552:Swine
chemical_list: D012333:RNA, Messenger; D012996:Solutions; D008315:Malondialdehyde; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin