Evidence for a mitochondrial impact of trimetazidine during cold ischemia and reperfusion

Pharmacology. 2004 May;71(1):25-37. doi: 10.1159/000076259.

Abstract

In organ transplantation, ischemia-reperfusion injury (IRI) has been implicated in delayed graft function (DGF) as well as in short- and long-term complications. Using an autotransplant pig kidney model, changes in renal function and morphology were determined after different periods of cold ischemia in kidneys preserved in the University of Wisconsin solution (UW), high-Na(+) version of UW (HEH) or Celsior (CEL) a newly developed high-Na(+) solution, with or without trimetazidine (TMZ). Kidney function was better preserved in CEL, UW and particularly HEH in combination with TMZ, particularly after 48 and 72 h. Mitochondria integrity was improved in TMZ-preserved groups. This study indicates that TMZ is efficiently protective against IRI even after prolonged preservation and in different preservation solutions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / pharmacology
  • Allopurinol / pharmacology
  • Animals
  • Biomarkers
  • Cryopreservation*
  • Disaccharides / pharmacology
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Electrolytes / pharmacology
  • Glutamates / pharmacology
  • Glutathione / pharmacology
  • Histidine / pharmacology
  • Insulin / pharmacology
  • Kidney Function Tests / methods
  • Kidney Transplantation / methods
  • Kidney Transplantation / mortality
  • Mannitol / pharmacology
  • Mitochondria / drug effects*
  • Mitochondria / physiology
  • Mitochondria / ultrastructure
  • Organ Preservation / methods
  • Organ Preservation Solutions / pharmacology
  • Raffinose / pharmacology
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / physiology
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / prevention & control
  • Swine
  • Time Factors
  • Transplantation, Autologous / methods
  • Transplantation, Autologous / mortality
  • Trimetazidine / pharmacology*

Substances

  • Biomarkers
  • Celsior
  • Disaccharides
  • Electrolytes
  • Glutamates
  • Insulin
  • Organ Preservation Solutions
  • Receptors, GABA-A
  • University of Wisconsin-lactobionate solution
  • Mannitol
  • Histidine
  • Allopurinol
  • Glutathione
  • Adenosine
  • Raffinose
  • Trimetazidine