Enhancement of procainamide-induced rate-dependent conduction slowing by elevated myocardial extracellular potassium concentration in vivo.
Procainamide, a type 1A antiarrhythmic drug, blocks sodium channels and reduces the maximum rate of rise of the cardiac action potential (Vmax) in a rate-dependent fashion. In vitro, the magnitude of this rate-dependent reduction in Vmax is greater in tissue that is partially depolarized at rest than in tissue with a normal resting potential. Reductions in Vmax produced by drugs that block sodium channels are also directly related to the reductions in longitudinal conduction velocity of action potential propagation in papillary muscle preparations. We therefore sought to determine whether the rate-dependent conduction slowing induced by procainamide in the intact canine heart is enhanced in myocardial tissue abnormally depolarized by an elevated myocardial extracellular potassium concentration, [K+]o. QRS duration and epicardial activation times were measured as indexes of myocardial conduction. QRS duration and epicardial activation times were measured at control (4.0 mM) and at intermediate (6.5 mM) and high (9.2 mM) myocardial [K+]o in the presence or absence of a clinically relevant procainamide concentration (12.2 +/- 2.6 g/ml) at the longest obtainable interstimulus interval of 440 msec and at 330, 280, and 250 msec. Intermediate and high myocardial [K+]o alone induced rate-dependent conduction slowing as the frequency of stimulation increased (cycle length 440 msec to 330, 280, and 250 msec). In the presence of procainamide, rate-dependent conduction slowing was observed at all levels of myocardial [K+]o, and the amount of rate-dependent change in conduction time increased as the myocardial [K+]o was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Cascio
W E
WE
Department of Medicine, University of North Carolina at Chapel Hill 27599.
Foster
J R
JR
Buchanan
J W
JW
Johnson
T A
TA
Gettes
L S
LS
D000200:Action Potentials; D000704:Analysis of Variance; D000818:Animals; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004562:Electrocardiography; D006329:Heart Conduction System / Q000187:drug effects*; D007263:Infusions, Parenteral; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D011189:Potassium Chloride / Q000008:administration & dosage; D011342:Procainamide / Q000008:administration & dosage / Q000494:pharmacology*
D011189:Potassium Chloride; D011342:Procainamide; D011188:Potassium