title: Potassium channel openers prevent potassium-induced calcium loading of cardiac cells: possible implications in cardioplegia.
abstract: Hyperkalemic solutions that are used as cardioplegic agents, while effective in inducing electromechanical arrest, are only partially cardioprotective, and ventricular dysfunction has been observed. The underlying pathophysiology of cardioplegia-associated ventricular dysfunction is complex and not fully understood, but it could be related, in part, to intracellular Ca2+ loading induced by high K+ concentrations present in cardioplegic solutions. Yet no effective cytoprotective means against possible intracellular Ca2+ loading, under these conditions, has been described. Recently, potassium channel openers, which open adenosine triphosphate-sensitive K+ channels, have been reported to possess cardioprotective properties under global ischemic conditions. However, it is not known whether these novel agents could prevent intracellular Ca2+ loading that could occur during cardioplegia. Intracellular Ca2+ was monitored in ventricular myocytes, loaded with the Ca(2+)-sensitive fluorescent probe Fluo-3AM, using epifluorescent digital imaging and laser confocal microscopy. Exposure of a myocyte to a 16 mmol/L concentration of K+, a concentration of K+ commonly used in cardioplegic solutions, induced a nonhomogeneous increase in intracellular Ca2+. Potassium channel opening drugs, such as aprikalim or nicorandil, effectively prevented these solutions from increasing intracellular Ca2+. The preventive effect of potassium channel opening drugs was antagonized by glyburide, a selective blocker of adenosine triphosphate-sensitive K+ channels. This study demonstrates, at the single cardiac cell level, that solutions containing a 16 mmol/L concentration of K+ promote intracellular Ca2+ loading, which can be prevented by potassium channel opening drugs. Therefore, potassium channel opening drugs should be considered to prevent intracellular Ca2+ loading associated with the use of cardioplegic solutions.
authors.affiliation: Department of Internal Medicine, Mayo Clinic, Rochester, Minn 55905, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: López
authors.forename: R
authors.initials: R
authors.lastname: Jahangir
authors.forename: A
authors.initials: A
authors.lastname: Jahangir
authors.forename: W K
authors.initials: WK
authors.lastname: Shen
authors.forename: A
authors.initials: A
authors.lastname: Terzic
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000814:Aniline Compounds; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002314:Cardioplegic Solutions / Q000008:administration & dosage / Q000009:adverse effects; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006324:Heart Arrest, Induced; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D006982:Hypertonic Solutions / Q000008:administration & dosage / Q000009:adverse effects; D007091:Image Processing, Computer-Assisted; D015640:Ion Channel Gating / Q000187:drug effects*; D018613:Microscopy, Confocal; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil; D010847:Picolines / Q000494:pharmacology; D011188:Potassium / Q000008:administration & dosage / Q000009:adverse effects; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects*; D011714:Pyrans / Q000494:pharmacology; D018754:Ventricular Dysfunction / Q000209:etiology / Q000503:physiopathology; D014966:Xanthenes
chemical_list: D000814:Aniline Compounds; D002121:Calcium Channel Blockers; D002314:Cardioplegic Solutions; D005456:Fluorescent Dyes; D006982:Hypertonic Solutions; D010847:Picolines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011714:Pyrans; D014966:Xanthenes; C059715:Fluo-3; D009536:Niacinamide; D020108:Nicorandil; C061043:aprikalim; D000255:Adenosine Triphosphate; D011188:Potassium; D005905:Glyburide; D002118:Calcium