title: Characterization of concentration- and use-dependent effects of quinidine from conduction delay and declining conduction velocity in canine Purkinje fibers.
abstract: 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.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: D L
authors.initials: DL
authors.lastname: Packer
authors.forename: A O
authors.initials: AO
authors.lastname: Grant
authors.forename: H C
authors.initials: HC
authors.lastname: Strauss
authors.forename: C F
authors.initials: CF
authors.lastname: Starmer
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects*; D009407:Nerve Block; D011674:Pulse / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D011802:Quinidine / Q000008:administration & dosage / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects*
chemical_list: D015222:Sodium Channels; D011802:Quinidine