Circulation, Vol 74, 1156-1167, Copyright © 1986 by American Heart Association
M Talajic and S Nattel
Calcium-channel blockers are known to affect slow inward current in a
frequency-dependent fashion. The purpose of these experiments was to study
use-dependent effects of verapamil, diltiazem, and nifedipine on
atrioventricular conduction in vivo. Loading and maintenance infusion
techniques were developed to study each drug at a series of stable plasma
concentrations in autonomically blocked dogs anesthetized with morphine and
alpha-chloralose. All three agents produced changes in atrioventricular
conduction and refractoriness that increased with increasing stimulation
frequency. The time dependence of drug-induced changes in atrioventricular
conduction was characterized both by varying the coupling of single test
stimuli and by abruptly changing activation frequency. The time constants
for onset of (tau on) and recovery from (tau off) block were typical for
each drug, with nifedipine having a faster time constant (tau off = 0.36
+/- 0.12 sec) than verapamil (tau off = 3.2 +/- 1.0 sec, tau on = 28 +/- 8
sec) or diltiazem (tau off = 2.7 +/- 1.2 sec, tau on = 13 +/- 4 sec). The
time constants for each drug were independent of concentration but the
magnitude of time-dependent change increased with increasing drug
concentration. We conclude that calcium-channel blockers have important
frequency-dependent effects on atrioventricular conduction in vivo. This
frequency dependence may result in selective depression of atrioventricular
conduction in the presence of supraventricular tachyarrhythmias, with
important potential implications for the clinical use of these agents.
ARTICLES
Frequency-dependent effects of calcium antagonists on atrioventricular conduction and refractoriness: demonstration and characterization in anesthetized dogs
This article has been cited by other articles:
 |
|
 |
|
  L. Rivard, H. Sinno, A. Shiroshita-Takeshita, G. Schram, T.-K. Leung, and S. Nattel The pharmacological response of ischemia-related atrial fibrillation in dogs: Evidence for substrate-specific efficacy Cardiovasc Res, April 1, 2007; 74(1): 104 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Ballo, D. Bernabo, and S. A. Faraguti Heart rate is a predictor of success in the treatment of adults with symptomatic paroxysmal supraventricular tachycardia Eur. Heart J., August 1, 2004; 25(15): 1310 - 1317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Garattini, E. Parrella, L. Diomede, M. Gianni', Y. Kalac, L. Merlini, D. Simoni, R. Zanier, F. F. Ferrara, I. Chiarucci, et al. ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis Blood, January 1, 2004; 103(1): 194 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Hassan, H. Oral, C. Scharf, A. Chugh, F. Pelosi, B. P. Knight, S. A. Strickberger, and F. Morady Rate-dependent effect of verapamil on atrial refractoriness J. Am. Coll. Cardiol., February 5, 2003; 41(3): 446 - 451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Sticherling, H. Tada, W. Hsu, A. C. Bares, H. Oral, F. Pelosi, B. P. Knight, S. A. Strickberger, and F. Morady Effects of Diltiazem and Esmolol on Cycle Length and Spontaneous Conversion of Atrial Fibrillation Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2002; 7(2): 81 - 88. [Abstract] [PDF]
|
|
|
|
|
|
A. Benardeau, S. Fareh, and S. Nattel Effects of verapamil on atrial fibrillation and its electrophysiological determinants in dogs Cardiovasc Res, April 1, 2001; 50(1): 85 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fareh, A. Benardeau, and S. Nattel Differential efficacy of L- and T-type calcium channel blockers in preventing tachycardia-induced atrial remodeling in dogs Cardiovasc Res, March 1, 2001; 49(4): 762 - 770. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nattel, C. Matthews, E. De Blasio, W. Han, D. Li, and L. Yue Dose-Dependence of 4-Aminopyridine Plasma Concentrations and Electrophysiological Effects in Dogs : Potential Relevance to Ionic Mechanisms In Vivo Circulation, March 14, 2000; 101(10): 1179 - 1184. [Abstract] [Full Text] [PDF]
|
|