Direct quantification of apparent binding indices from quinidine-induced in vivo conduction delay in canine myocardium

Frank N. Haugland, Susan B. Johnson, Douglas L. Packer

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

To characterize quantitatively the quinidine (QUIN)-induced conduction delay (CD) in vivo, canine ventricular activation times were examined with an epicardial mapping technique. A high-resolution index of normalized (N) QUIN CD, derived from all 56 recording sites, was used to quantify QUIN effect. Repetitive stimulation elicited monoexponential increases in CD(N), the rates of which were a linear function of interpulse recovery interval, t(r). Steady-state CD(N) was also linearly related to an exponential function of t(r) and drug uptake rates. The frequency-dependent properties of QUIN in 14 dogs were characterized by apparent binding and unbinding rates of k(a) = 7.1±3.5 x 106 M-1 s-1, l(a) = 81±51 s-1 for activated, and k(r) = 12.6±11.3 x 103 M-1 s-1, l(r) = 0.51±0.26 s-1 for resting states. k(a) and l(a) were similar to values previously derived in canine Purkinje fibers. During unbinding at resting potentials was faster in vivo than previously observed in vitro. The time constant of recovery from QUIN block extracted from the interpulse recovery rate was also identical to that determined from post-mature stimulus diastolic scanning. As predicted by the two-state model, similar binding rates were also derived from declining CD(N) elicited by step decreases in heart rate. These findings represent a complete quantitative description of use-dependent QUIN CD in vivo and provide a firm foundation for characterizing antiarrhythmic drug action under physiologic and pathologic conditions.

Original languageEnglish (US)
Pages (from-to)1798-1811
Number of pages14
JournalJournal of Clinical Investigation
Volume93
Issue number4
DOIs
StatePublished - Apr 1994

Keywords

  • antiarrhythmia agents
  • electromechanical coupling
  • electrophysiology
  • sodium channels
  • use dependence

ASJC Scopus subject areas

  • Medicine(all)

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