PROTECTION OF ISCHAEMIC-REPERFUSED RAT HEART BY DIMETHYLAMILORIDE IS ASSOCIATED WITH INHIBITION OF MITOCHONDRIAL PERMEABILITY TRANSITION

SUMMARY 1 The aim of the present study was to assess whether protection afforded by the Na+/H+ exchanger blocker dimethylamiloride (DMA) is associated with inhibition of mitochondrial permeability transition (MPT). The effects of DMA were compared with those of cyclosporine (Cs) A, an inhibitor of MPT. 2 Rat hearts were Langendorff perfused with Krebs’–bicarbonate medium containing 10 mmol/L glucose and were subjected to 25 min no‐flow global ischaemia and 30 min reperfusion in the presence or absence of 10 µmol/L DMA or 0.2 µmol/L CsA. Cell viability was measured using tetrazolium stain. The MPT was determined by loading hearts with 2‐deoxy‐[3H]‐glucose (2DG), which enters mitochondria only during MPT. Total heart 2DG content as an estimation of the extent of tissue damage was also measured. To assess whether DMA has any direct effect on glycolysis, a cell‐free heart extract containing all the glycolytic enzymes was used. 3 Dimethylamiloride improved functional recovery (rate–pressure product) from 24 ± 7 to 68 ± 11% (P