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 (pH_i), 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 pH_i 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.