Protective role of magnesium in catecholamine-induced arrhythmia and toxicity in vitro.
The present study examined the arrhythmogenic and toxic liability of isoprenaline, noradrenaline and adrenaline using a model of spontaneously beating, cultured rat cardiomyocytes. The cardioprotective role of magnesium (Mg) was also evaluated. Following two hours of exposure to 0.1-2.7 mM doses of isoprenaline, noradrenaline or adrenaline, there were dose-dependent increases in the incidence of arrhythmia and decreases in beating activity. Myocyte LDH release increased 64-189% while total myocyte K+ and Mg2+ decreased 13-60% at high catecholamine doses. Levels of the secondary messengers IP3 and cAMP were also increased. Equimolar Mg (0.9 mM) significantly reduced the incidence of catecholamine arrhythmia while preserving beating activity, membrane integrity and electrolyte levels. Mg proved to be in vitro a potent antiarrhythmic and cardioprotective agent which is likely to exert its beneficial effects via antagonism of calcium.
Zdanowicz
M M
MM
College of Pharmacy and Allied Health, St. John's University, Jamaica, New York 11439.
Barletta
M A
MA
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D002395:Catecholamines / Q000633:toxicity*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000633:toxicity; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis; D007545:Isoproterenol / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000187:drug effects; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000166:cytology; D009638:Norepinephrine / Q000633:toxicity; D011188:Potassium / Q000378:metabolism; D051381:Rats
D002395:Catecholamines; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D007770:L-Lactate Dehydrogenase; D008274:Magnesium; D007545:Isoproterenol; D011188:Potassium; D009638:Norepinephrine; D004837:Epinephrine