Previous fasting (24 h) improves functional recovery and reduces ischemic lactate accumulation in rat hearts subjected to 25 min no flow global ischemia (I)-30 min reperfusion (RP), without affecting cell viability. On the other hand, the Na⁺/H⁺ exchanger blocker dimethylamiloride (DMA) improved functional recovery and reduced ischemic lactate accumulation in hearts from fed rats abolishing the differences between both groups. However, it improved cell viability in both nutritional states. In order to assess whether inhibition of mitochondrial permeability transition (MPT) is involved in the aforementioned effects of DMA. Langendorff perfused hearts from fed ad libitum or fasted rats were subjected to 25 min I and 30 min RP. 10 mM DMA was added to perfusion medium 10 min before the onset of I until 3 min RP. MPT was determined by loading the hearts with 0.5 mM 2-deoxy [3H] glucose (2DG) (0.1 mCi/mL), which enters mitochondria only during MPT. Fed vs Fasted 30 min RP: Control: 105xRatio of mitochondrial [3H]d.p.m per unit of citrate synthase to total heart [3H]d.p.m/gww 96.3±14.02; 86.25±11.57; Total 2DG uptake 103xd.p.m/gww 51.3±4.47, 45.36±3.47; Mitochondrial yield CS units/gww 10.3±0.81, 15.77±2.01. DMA: 105xRatio of mitochondrial [3H]d.p.m per unit of citrate synthase to total heart [3H]d.p.m/gww 33.1±14.21** , 62.65±14.35*; Total 2DG uptake 103xd.p.m/gww 86.8±1.75*, 78.54±10.07*; Mitochondrial yield CS units/gww 20.1±0.85*, 17.19±1.49. Data are presented as mean values±S.E.M. (n=8). **p <0.01; *p<0.05 vs control 30 min RP.

Present data suggest that the cardioprotective effect mediated by DMA is mediated, at least in part, by the inhibition of MPT.