Skip to main content

Characterization of concentration- and use-dependent effects of quinidine from conduction delay and declining conduction velocity in canine Purkinje fibers.

Publication ,  Journal Article
Packer, DL; Grant, AO; Strauss, HC; Starmer, CF
Published in: J Clin Invest
June 1989

The dynamic response of squared conduction velocity, theta 2, to repetitive stimulation in canine Purkinje fibers with quinidine was studied using a double-microelectrode technique. With stimulation, a frequency-dependent monoexponential increase in conduction delay (CD) and a decline in theta 2 were observed. The exponential rates and changes in steady-state CD and theta 2 were frequency- and concentration-dependent. The overall drug uptake rates describing blockade and the interpulse recovery interval were linearly related and steady-state values of theta 2 were linearly related to an exponential function of the stimulus intervals. Based on first-order binding, the frequency- and concentration-dependent properties of quinidine were characterized by the apparent binding and unbinding rates of 14.2 +/- 5.7 X 10(6) mol-1.s-1 and 63 +/- 12 s-1 for activated and 14.8 +/- 1.0 X 10(2) mol-1.s-1 and 0.16 +/- 0.03 s-1 for resting states. The recovery time constant extracted from the pulse train interpulse interval was 5.8 +/- 1.5 s compared with 5.1 +/- 0.6 s determined from a posttrain test pulse protocol. This study demonstrates that the kinetics of drug action can be derived from measures of impulse propagation. This provides a basis for characterizing frequency-dependent properties of antiarrhythmic agents in vivo and suggests the plausibility of a quantitative assessment of drug binding and recovery rates in man.

Duke Scholars

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

June 1989

Volume

83

Issue

6

Start / End Page

2109 / 2119

Location

United States

Related Subject Headings

  • Sodium Channels
  • Quinidine
  • Purkinje Fibers
  • Pulse
  • Nerve Block
  • Membrane Potentials
  • Kinetics
  • Immunology
  • Heart Conduction System
  • Electric Stimulation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Packer, D. L., Grant, A. O., Strauss, H. C., & Starmer, C. F. (1989). Characterization of concentration- and use-dependent effects of quinidine from conduction delay and declining conduction velocity in canine Purkinje fibers. J Clin Invest, 83(6), 2109–2119. https://doi.org/10.1172/JCI114124
Packer, D. L., A. O. Grant, H. C. Strauss, and C. F. Starmer. “Characterization of concentration- and use-dependent effects of quinidine from conduction delay and declining conduction velocity in canine Purkinje fibers.J Clin Invest 83, no. 6 (June 1989): 2109–19. https://doi.org/10.1172/JCI114124.
Packer, D. L., et al. “Characterization of concentration- and use-dependent effects of quinidine from conduction delay and declining conduction velocity in canine Purkinje fibers.J Clin Invest, vol. 83, no. 6, June 1989, pp. 2109–19. Pubmed, doi:10.1172/JCI114124.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

June 1989

Volume

83

Issue

6

Start / End Page

2109 / 2119

Location

United States

Related Subject Headings

  • Sodium Channels
  • Quinidine
  • Purkinje Fibers
  • Pulse
  • Nerve Block
  • Membrane Potentials
  • Kinetics
  • Immunology
  • Heart Conduction System
  • Electric Stimulation