Effects of Trimetazidine on Lipid Peroxidation and Phosphorus Metabolites during Cold Storage and Reperfusion of Isolated Perfused Rat Kidneys1
- Th. Hauet1,2,
- G. Bauza2,
- J. M. Goujon1,
- J. C. Caritez1,
- M. Carretier1,
- M. Eugene2 and
- J. P. Tillement3
- 1Groupe de Recherche en Transplantation Multiviscérale-Institut National de Recherche Agronomique, Domaine du Magneraud (Th.H, J.M.G., J.C.C., M.C.), Surgères, France; 2Laboratoire de RMN et Explorations Fonctionnelles (Th.H., G.B., M.E.), Hôpital Saint-Louis, Paris, France; and 3Laboratoire de Pharmacologie (J.P.T.), Faculté de Médecine, Paris XII, Creteil, France
Abstract
This study was undertaken to evaluate the effect of trimetazidine (TMZ) during cold storage (CS) and the consequence during normothermic reperfusion in an isolated perfused rat kidney model (IPK). IPK was used to assess the rate of perfusion flow, the ratio of ATP to inorganic phosphate (ATP/Pi) as a reflection of the energetic status during reperfusion, intracellular pH (pHi), tissue water content and malondialdehyde (MDA) tissue levels in four different preservation solutions after 48-hr preservation at 4°C and 2-hr reperfusion at 37.5°C: EuroCollins (EC), University of Wisconsin (UW), EC plus TMZ (10−6 M) (EC + TMZ) and UW plus TMZ (10−6 M) (UW + TMZ). When TMZ was added to the preservation solutions, perfusion flow rate (PFR) was significantly improved during reperfusion. Tissue water content, which reflected tissue edema, was significantly lower in TMZ groups than in groups without TMZ during both CS and reperfusion conditions. In TMZ groups, ATP/Pi ratio was also significantly improved during CS and reperfusion. In addition, TMZ lowered the pHi both during preservation and after reperfusion. MDA renal tissue level significantly decreased with TMZ both during the preservation period and after reperfusion. These overall results strongly suggested that TMZ contributes to renal protection from cold ischemia-reperfusion injury in this IPK model, especially when TMZ was added to UW solution and during prolonged hypothermic ischemia.
Footnotes
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Send reprint requests to: Dr. Th. Hauet, Service de Nephrologie, Hôpital Saint Louis, Centre Hospitalier de La Rochelle, 17019 La Rochelle, France.
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↵1 This work was supported by grants from the Ministère de la Recherche (92C0746) and de l’Education Nationale (EA 427), the Association pour le developpement de la Dialyse àDomicile (ADA 17) and the Institut de Recherches Internationales SERVIER.
- Abbreviations:
- ATP/Pi
- ATP to inorganic phosphate ratio
- CS
- cold storage
- IPK
- isolated perfused rat kidney
- EC
- EuroCollins solution
- EC + TMZ
- EuroCollins solution plus trimetazidine
- MDA
- malondialdehyde
- PCr
- phosphocreatine
- Pi
- inorganic phosphate
- pHi
- intracellular pH
- PFR
- perfusion flow rate
- NMR
- nuclear magnetic resonance
- ROS
- reactive oxygen species
- TMZ
- trimetazidine
- UW
- University of Wisconsin solution
- UW + TMZ
- University of Wisconsin solution plus trimetazidine
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- Received September 4, 1997.
- Accepted January 20, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
