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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Packer, DL; Grant, AO; Strauss, HC; Starmer, CF

Published Date

  • June 1989

Published In

Volume / Issue

  • 83 / 6

Start / End Page

  • 2109 - 2119

PubMed ID

  • 2542382

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI114124

Language

  • eng

Conference Location

  • United States