title: Depressant effect of magnesium on early afterdepolarizations and triggered activity induced by cesium, quinidine, and 4-aminopyridine in canine cardiac Purkinje fibers.
abstract: Magnesium chloride has been shown to terminate torsades de pointes in some patients with the acquired long QT syndrome. The mechanism for this effect is unknown. Recently early afterdepolarizations (EADs) and triggered activity (TA) have been proposed as causes of torsades de pointes. The purpose of the present study was to examine whether magnesium suppressed EADs that were initiated in vitro by different agents and if so its mechanism of action. TA arising from EADs was induced by quinidine (1 to 4 mumol/L, n = 5) at high temperature (38.5 to 40 degrees C), cesium chloride (5 to 12 mmol/L, n = 6), and 4-aminopyridine (1.5 to 5 mmol/L, n = 7) in canine cardiac Purkinje fibers superfused with modified Tyrode's solution (KCI = 2.7 mmol/L). MgCl2 (2 to 7 mmol/L) reversibly abolished TA and suppressed EADs. Tetrodotoxin (TTX; 1 to 5 mumol/L) also abolished TA elicited by 4-aminopyridine (n = 6). We then examined the effects of MgCl2, TTX, and verapamil on depolarization-induced automaticity by means of a single sucrose gap technique to gain insight into the mechanism of action of magnesium. MgCl2 (5 mmol/L) abolished automaticity arising from membrane potentials more negative than -70 mV and prolonged the spontaneous cycle length at less negative membrane potentials. The effects of TTX (1 to 5 mumol/L) resembled those of MgCl2. Verapamil (1 mumol/L) prolonged the cycle length of the initial automatic response at high levels of membrane potential and progressively reduced the amplitude of the subsequent automatic potentials. It abolished automaticity arising from less negative membrane potentials.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis.
authors.forename: S
authors.initials: S
authors.lastname: Kaseda
authors.forename: R F
authors.initials: RF
authors.lastname: Gilmour
authors.forename: D P
authors.initials: DP
authors.lastname: Zipes
mesh_terms: D015761:4-Aminopyridine; D000200:Action Potentials / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology*; D003864:Depression, Chemical; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D011802:Quinidine / Q000494:pharmacology*; D013610:Tachycardia / Q000188:drug therapy
chemical_list: D000631:Aminopyridines; D002317:Cardiovascular Agents; D002586:Cesium; D015761:4-Aminopyridine; D008274:Magnesium; D011802:Quinidine