Efficiency of trimetazidine in renal dysfunction secondary to cold ischemia-reperfusion injury: a proposed addition to University of Wisconsin solution.
Nonspecific injury in cadaveric renal transplants adversely affects early graft function and influences long-term graft survival after organ transplantation. Trimetazidine (TMZ) has been reported to exert a protective action against normothermic ischemia and reperfusion injury in several experimental and clinical studies. In an isolated perfused pig kidney model, we investigated the effects of TMZ added to University of Wisconsin solution (UW) during 48 or 72 h of cold storage (CS) and the consequence during reperfusion. Under all conditions tested renal perfusate flow rate (PFR), renal functions, and tubular injury markers were determined during a 120-min perfusion period. Lipid peroxidation and histological examination (optical and electron microscopy) were also determined after CS and reperfusion. The addition of TMZ (10(-6) M) to the UW solution improved dramatically the quality of preserved kidneys and consequently the functional recovery during reperfusion. TMZ + UW also significantly had a protecting role against reperfusion injury and lipid peroxidation when compared to UW alone. These results were correlated with both a better preservation of the proximal brush border membrane and reduced cellular and mitochondrial swelling. These results also suggested that the TMZ-induced renoprotection correlated well with the observed decrease membrane lipid peroxidation. Therefore, trimetazidine may be useful for clinical kidney graft preservation.
Hauet
T
T
Unité de Chirurgie expérimentale, Département de Génétique animale, Institut National de Recherche Agronomique, Le Magneraud, Surgeres, 17000, France.
Tallineau
C
C
Goujon
J M
JM
Carretier
M
M
Eugene
M
M
Tillement
J P
JP
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D019343:Citric Acid / Q000378:metabolism; D003080:Cold Temperature; D005919:Glomerular Filtration Rate; D005978:Glutathione; D006801:Humans; D007328:Insulin; D007668:Kidney / Q000187:drug effects* / Q000293:injuries* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000502:physiology; D007684:Kidney Tubules / Q000503:physiopathology; D019344:Lactic Acid / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D010477:Perfusion; D011887:Raffinose; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine; D014292:Trimetazidine / Q000494:pharmacology*
D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D019343:Citric Acid; D019344:Lactic Acid; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D014292:Trimetazidine