TY - JOUR
T1 - Potassium channel openers prevent potassium-induced calcium loading of cardiac cells
T2 - Possible implications in cardioplegia
AU - Lopez, J. R.
AU - Jahangir, R.
AU - Jahangir, A.
AU - Shen, W. K.
AU - Terzic, A.
N1 - Funding Information:
This study was supported by grants from the American Heart Association, the National Heart Foundation (Rockville, Md.), and the Pharmaceutical Research and Manufacturers of America Foundation (Washington, D.C.).
PY - 1996
Y1 - 1996
N2 - 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 Ca2+-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.
AB - 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 Ca2+-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.
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U2 - 10.1016/S0022-5223(96)70070-3
DO - 10.1016/S0022-5223(96)70070-3
M3 - Article
C2 - 8800173
AN - SCOPUS:0029908195
SN - 0022-5223
VL - 112
SP - 820
EP - 831
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 3
ER -