title: Role of intracellular calcium in the antiarrhythmic effect of procainamide during ventricular fibrillation in rat hearts.
abstract: Increased intracellular calcium (calcium overload) is considered one of the factors that can initiate ventricular fibrillation. In addition, ventricular fibrillation itself can cause and possibly maintain calcium overload. The goal of this study was to determine whether the class IA antiarrhythmic agent procainamide can reduce calcium overload during ventricular fibrillation and, if so, whether this reduction could be responsible for the recovery of the left ventricular function after defibrillation. For this purpose, the effects of 0.1 mmol/L of procainamide perfusion on left ventricular developed pressure, cardiac rate, and intracellular calcium during pacing-induced ventricular fibrillation were measured in isolated perfused rat hearts. Intracellular calcium was assessed by surface fluorometry after indo 1 loading. The concentration of procainamide was selected such that approximately half of the hearts would functionally recover from fibrillation. Cardiac rate and intracellular calcium were compared among four groups, depending on both the perfusate used and the recovery of left ventricular developed pressure at the end of the experiment. We found that procainamide reduced intracellular calcium to steady-state levels in hearts in which left ventricular function completely recovered (developed pressure > 67% of the steady-state value). However, intracellular calcium remained elevated in partially recovered hearts (33% < or = pressure < or = 67%) and in nonrecovered hearts (pressure < 33%). Thus procainamide can reduce calcium overload during ventricular fibrillation, and this reduction could be responsible for the recovery of left ventricular function after defibrillation. This reduction was use dependent, that is, dependent on high cardiac rates during fibrillation rather than on the decrease of cardiac rates before or during defibrillation.
authors.affiliation: Department of Medicine, University of California, San Francisco 94143-0124, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Zaugg
authors.forename: S T
authors.initials: ST
authors.lastname: Wu
authors.forename: S
authors.initials: S
authors.lastname: Kojima
authors.forename: J
authors.initials: J
authors.lastname: Wikman-Coffelt
authors.forename: W W
authors.initials: WW
authors.lastname: Parmley
authors.forename: P T
authors.initials: PT
authors.lastname: Buser
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D005470:Fluorometry; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D011342:Procainamide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014693:Ventricular Fibrillation / Q000378:metabolism* / Q000503:physiopathology; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D011342:Procainamide; D002118:Calcium