Effects of 5-hydroxydecanoate and ischemic preconditioning on the ischemic-reperfused heart of fed and fasted rats

Abstract

This investigation aimed to assess whether the mitochondrial ATP-sensitive potassium channel blocker 5-hydroxydecanoate (5-HD) could abolish the protection conferred by fasting and ischemic preconditioning (IPC) and to ascertain whether these effects are associated with glycogen breakdown and glycolytic activity. Langendorff perfused hearts of fed and 24-h fasted rats were exposed to 25 min ischemia plus 30 min reperfusion. IPC was achieved by a 3 min ischemia plus a 5 min reperfusion cycle. 5-HD (100 microM) perfusion begun 5 min before IPC or 13 min before sustained ischemia in the non preconditioned groups. Fasting improved the reperfusion recovery of contraction, decreased the contracture and the lactate production, increased glycogenolysis and did not affect the percentage of viable tissue. 5-HD abolished the effects of fasting on the contractile recovery but did not affect the contracture. 5-HD decreased the lactate production in the fed group, increased the preischemic glycogen content in both nutritional groups and did not affect the ischemic glycogen fall. IPC improved the contractile function but prevented the contracture only in the fed group, reduced lactate accumulation and glycogenolysis and evoked an increase of the viable tissue. 5-HD abolished the effects of IPC on the contractile recovery and did not affect its effect on the contracture, lactate production, glycogenolysis and viable tissue. These data suggest that the mitocondrial ATP-sensitive potassium channel is involved in the effects of fasting and IPC on the contractile function but the other cardioprotective and metabolic effects appear evoked through other mechanisms. Also suggest that besides the inhibition of the mitochondrial potassium channel, other mechanisms mediate the effects of 5-HD.

Involvement of Mitochondrial Permeability Transition, Glutathione Status, Pentose Phosphate Pathway and Oxidative Damage in the Protective Effect of Fasting on the Ischaemic‐reperfused Rat Heart

“…This is associated with an improved functional recovery following a period of ischaemia in hearts from fasted rats, as reported previously. [1][2][3][4][5][6] This suggests that the glutathione status of the heart The results of the present study agree with the data of Blaustein et al, 31 who observed that functional recovery was impaired in hearts that had been depleted of glutathione and were exposed to 20 min total global ischaemia. In contrast.…”

“…It is likely that this shift of metabolism towards the pentose phosphate pathway also occurs in hearts isolated from fasted rats, because both previously reported and current data indicate that fasting increases the oxidation of fatty acids derived from endogenous TAG and also decreases lactate production. 2,3,6,8 The heart has a large requirement for NADPH, which is needed to maintain the tissue content of GSH in order to counteract the oxidative stress that results mainly from the production of ROS in the mitochondria. Given that the capacity of the oxidative pentose phosphate pathway in the heart is very limited, 38 the myocardium has no efficient system to detoxify oxygen free radicals produced during reperfusion.…”

“…However, the cellular and molecular mechanisms that underlie this cardioprotective effect are not fully understood. [1][2][3][4][5][6][7] Marina Prendes et al [5][6][7] reported that the beneficial effects of previous fasting on rat hearts that were subsesquently perfused by the Langendorff method and exposed to global ischaemia-reperfusion (I/R) were associated with a higher pre-ischaemic glycogen content and increased glycogen utilization during ischaemia, together with a reduced accumulation of lactate, compared with hearts from fed rats. In agreement with earlier reports, inhibition of the Embden-Meyerhoff pathway is likely to be caused by the increased oxidation of fatty acids, derived from endogenous triacylglycerol (TAG), which is known to occur in aerobic isolated heart from fasted rats.…”

Cardiac metabolism as a driver and therapeutic target of myocardial infarction

“…182 It has been reported that fasting increased the myocardial BHB/AcAc ratio reflecting altered mitochondrial redox state and fasting of rats for only 24 hours improved the post-ischaemic recovery of contractile function and reduced the lactate dehydrogenase release in isolated hearts subjected to global IR. 183 In another study, short-term fasting increased the concentration of BHB and BHB/AcAc ratio compared to controls, limited the infarct size and reduced the total number of premature ventricular complexes and the duration of ventricular tachycardia occurring at early reperfusion. 184 However, low concentration of endogenous ketone bodies failed to preserve the myocardial ATP levels whereas exogenous supplementation (to 40 times the original concentration) prevented the loss of ATP by ischaemic injury.…”