Influence of fasting on the effects of dimethylamiloride and oxfenicine on ischaemic–reperfused rat hearts

Abstract

To assess whether glycolysis, Na⁺–H⁺ exchange and oxidation of fatty acid derived from endogenous lipolysis are involved in the beneficial effects of 24-h fasting on the ischaemic – reperfused heart, it was studied the effects of inhibiting Na⁺ – H⁺ exchange using 10 μM dimethylamiloride and fatty acid oxidation using 2 mM oxfenicine, on the functional activity, lactate production and cell viability measured with tetrazolium stain. Since fasting accelerates heart fatty acid oxidation, data were compared to those from fed rats; using Langendorff perfused (glucose 10 mM) hearts of 250–350 g Wistar rats exposed to 25 min ischaemia – 30 min reperfusion. Fasting reduced the ischaemic rise of end diastolic pressure (contracture), improved recovery of contraction and lowered lactate production in comparison with the fed whereas cellular viability was similar in both groups. Dimethylamiloride improved the recovery of contraction (fed control 24 ± 9%, fed treated 68 ± 11%, P < 0.05 at the end of reperfusion), attenuated the contracture (fed control 40 ± 9%, fed treated 24 ± 11%, P < 0.05 at the beginning of reperfusion) and reduced lactate production in the fed group and increased cellular viability in both groups (fed control 21 ± 6%, fed treated 69 ± 7%, P < 0.05, and fasted control 18 ± 7%, fasted treated 53 ± 8%, P < 0.05). Oxfenicine reduced the recovery of contraction (fasted control 88 ± 6%, fasted treated 60 ± 11%, P < 0.05) and increased lactate production of fasted group and attenuated the contracture in the fed. These data suggest that beneficial effects of fasting owe, at least in part, to a lowered glycolysis probably secondary to the increased fatty acid oxidation and to the accumulation of energy supplying acyl esters. Dimethylamiloride slowing of glycolysis might explain functional improvement, whereas it seems unrelated to the protection on cell viability.

Key words:  :

• Fasting
• heart
• ischemia
• oxfenicine
• dimethylamiloride