Potassium channel openers prevent potassium-induced calcium loading of cardiac cells: possible implications in cardioplegia

J Thorac Cardiovasc Surg. 1996 Sep;112(3):820-31. doi: 10.1016/S0022-5223(96)70070-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / antagonists & inhibitors
  • Adenosine Triphosphate / metabolism
  • Aniline Compounds
  • Animals
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Cardioplegic Solutions / administration & dosage
  • Cardioplegic Solutions / adverse effects
  • Cells, Cultured
  • Fluorescent Dyes
  • Glyburide / pharmacology
  • Guinea Pigs
  • Heart Arrest, Induced*
  • Heart Ventricles / cytology
  • Heart Ventricles / metabolism
  • Hypertonic Solutions / administration & dosage
  • Hypertonic Solutions / adverse effects
  • Image Processing, Computer-Assisted
  • Ion Channel Gating / drug effects*
  • Microscopy, Confocal
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Niacinamide / analogs & derivatives
  • Niacinamide / pharmacology
  • Nicorandil
  • Picolines / pharmacology
  • Potassium / administration & dosage
  • Potassium / adverse effects
  • Potassium Channel Blockers
  • Potassium Channels / drug effects*
  • Pyrans / pharmacology
  • Ventricular Dysfunction / etiology
  • Ventricular Dysfunction / physiopathology
  • Xanthenes


  • Aniline Compounds
  • Calcium Channel Blockers
  • Cardioplegic Solutions
  • Fluorescent Dyes
  • Hypertonic Solutions
  • Picolines
  • Potassium Channel Blockers
  • Potassium Channels
  • Pyrans
  • Xanthenes
  • Fluo-3
  • Niacinamide
  • Nicorandil
  • aprikalim
  • Adenosine Triphosphate
  • Potassium
  • Glyburide
  • Calcium