title: 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.
authors.affiliation: Department of Pharmacodynamids, Jagiellonian University, Medical College, Kraków, Poland. Electronic address: magda.dudek@uj.edu.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dudek
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Knutelska
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bednarski
authors.affiliation: Department of Pharmacodynamids, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Nowiński
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zygmunt
authors.affiliation: Chair of Medical Biochemistry, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bilska-Wilkosz
authors.affiliation: Chair of Medical Biochemistry, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Iciek
authors.affiliation: Department of Pharmacodynamids, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Otto
authors.affiliation: Department of Pharmacodynamids, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Żytka
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
authors.affiliation: Chair of Medical Biochemistry, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Włodek
authors.affiliation: Department of Pharmacodynamids, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Filipek
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006862:Hydrogen Sulfide / Q000378:metabolism; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D054086:KATP Channels; D024101:Mitochondrial Proteins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D020011:Protective Agents; D008063:Thioctic Acid; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat; D005905:Glyburide; D006862:Hydrogen Sulfide
keywords: Alpha lipoic acid; Hydrogen sulfide; Ischemia–reperfusion; K(ATP) channels; Sulfane sulfur