Alpha lipoic acid protects the heart against myocardial post ischemia–reperfusion arrhythmias via KATP channel activation in isolated rat hearts

Abstract

The cardiovascular effects of alpha lipoic acid were evaluated in isolated rat hearts exposed to ischemia-reperfusion injury in vitro. Alpha-lipoic acid raised the level of sulfane sulfur playing an important role in the release of hydrogen sulfide. H2S was shown to prevent the post-reperfusion arrhythmias and to protect the cardiomyocytes from death caused by hypoxia. The activation of potassium ATP-sensitive channels (K(ATP) channels) is one of the most important mechanisms of action of hydrogen sulfide in the cardiovascular system. The aim of this study was to investigate whether alpha lipoic acid can prevent the occurrence of post-reperfusion arrhythmias in vitro using a Langendorff model of ischemia-reperfusion in rats affecting the K(ATP) channels. Alpha lipoic acid significantly improved post-reperfusion cardiac function (reducing incidence of arrhythmias), especially in a dose of 10(-7)M. These cardiovascular effects of this compound on the measured parameters were reversed by glibenclamide, a selective K(ATP) blocker. Alpha lipoic acid increased the level of sulfane sulfur in the hearts. This may suggest that the positive effects caused by alpha lipoic acid in the cardiovascular system are not only related to its strong antioxidant activity, and the influence on the activity of such enzymes as aldehyde dehydrogenase 2, as previously suggested, but this compound can affect K(ATP) channels. It is possible that this indirect effect of alpha lipoic acid is connected with changes in the release of sulfane sulfur and hydrogen sulfide.

Alpha-Lipoic Acid Preconditioning and Ischaemic Postconditioning Synergistically Protect Rats from Cerebral Injury Induced by Ischemia and Reperfusion Partly via Inhibition TLR4/MyD88/ NF-κB Signaling Pathway

“…Due to its strong antioxidant effect, ALA has also been demonstrated to exert a similar protective effect in non-neuronal tissue as well. For instance, preconditioning or postconditioning with ALA is protective against I/RI-induced cardiac dysfunction, retinal damage, ovarian torsion injury and reperfusioninduced renal failure [25][26][27][28]. The latest clinical research has uncovered that the protective mechanisms of ALAP against simultaneous kidney-pancreas transplantation-induced renal dysfunction and post-transplant pancreatitis occur through its anti-inflammatory effects [29].…”

Hypotensive effect of alpha-lipoic acid after a single administration in rats

“…Other studies have shown that glibenclamide abolishes the decongestant action of alpha-lipoic acid, suggesting that ATP-dependent potassium channels are involved in this action (14, 15) and that this effect could be associated with the formation of H 2 S.…”

Penehyclidine hydrochloride protects against anoxia/reoxygenation injury in cardiomyocytes through ATP‐sensitive potassium channels, and the Akt/GSK‐3β and Akt/mTOR signaling pathways

“…KATP channels were first found in cardiac muscles in 1983 (Noma, 1983). Previous studies have revealed that mitochondrial KATP channels mediate the cardioprotection of other drugs (e.g., naringenin, alpha‐lipoic acid, and baicalein) against I/R injury (Chang et al, 2013; Dudek et al, 2014; Meng et al, 2016). Interestingly, in our study, we found that A/R activated mitochondrial KATP channels in H9c2 cells by upregulating the expression of channel subunits (Kir6.2 and SUR2A).…”