pH-dependent electrophysiological effects of quinidine and lidocaine on canine cardiac Purkinje fibers

S. Nattel, V. Elharrar, D. P. Zipes, J. C. Bailey

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

We used standard microelectrode techniques to evaluate the effects of lidocaine and quinidine on canine Purkinje fibers at normal pH (7.3) and in the presence of acidosis (pH 6.9). Acidosis alone reduced resting potential, action potential amplitude, and V̇max, while increasing APD90 and conduction time. Lidocaine concentrations of 6x10-6 to 1.5x10-5 M had minimal effect on resting potential, action potential amplitude, and V̇max at pH 7.3. At pH 6.9, the same lidocaine concentrations significantly reduced resting potential (3-10%), action potential amplitude (3-8%) and V̇max (14-22%). Quinidine (6x10-6 to 1.5x10-5 M) reduced resting potential (3-5%), action potential amplitude (4-9%), and V̇max (19-34%) at pH 7.3. At pH 6.9, quinidine produced significantly greater reductions in resting potential (4-15%), action potential amplitude (5-18%), and V̇max (22-49%). These changes were associated with much more quinidine- and lidocaine-induced prolongation of interelectrode conduction time at acidic than at normal pH. Inexcitability occurred at pH 6.9 in 4 of 14 experiments with 1.5x10-5 M quinidine and in 2 of 10 with 1.5x10-5 M lidocaine, and was reversed at the same drug concentration by normalizing pH. Acidosis did not alter the V̇max-resting potential relationship in either the absence or presence of antiarrhythmic agents. Furthermore, changes in ionization did not account for the alterations in electrophysiological effects of quinidine and lidocaine produced by acidosis. Our data suggest that extracellular pH changes may modify importantly the effects of antiarrhythmic agents.

Original languageEnglish
Pages (from-to)55-61
Number of pages7
JournalCirculation Research
Volume48
Issue number1
StatePublished - 1981

Fingerprint

Purkinje Fibers
Quinidine
Lidocaine
Canidae
Membrane Potentials
Action Potentials
Acidosis
Microelectrodes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Nattel, S., Elharrar, V., Zipes, D. P., & Bailey, J. C. (1981). pH-dependent electrophysiological effects of quinidine and lidocaine on canine cardiac Purkinje fibers. Circulation Research, 48(1), 55-61.

pH-dependent electrophysiological effects of quinidine and lidocaine on canine cardiac Purkinje fibers. / Nattel, S.; Elharrar, V.; Zipes, D. P.; Bailey, J. C.

In: Circulation Research, Vol. 48, No. 1, 1981, p. 55-61.

Research output: Contribution to journalArticle

Nattel, S, Elharrar, V, Zipes, DP & Bailey, JC 1981, 'pH-dependent electrophysiological effects of quinidine and lidocaine on canine cardiac Purkinje fibers', Circulation Research, vol. 48, no. 1, pp. 55-61.
Nattel, S. ; Elharrar, V. ; Zipes, D. P. ; Bailey, J. C. / pH-dependent electrophysiological effects of quinidine and lidocaine on canine cardiac Purkinje fibers. In: Circulation Research. 1981 ; Vol. 48, No. 1. pp. 55-61.
@article{2f99151e977e4d92beec4e063ed8119b,
title = "pH-dependent electrophysiological effects of quinidine and lidocaine on canine cardiac Purkinje fibers",
abstract = "We used standard microelectrode techniques to evaluate the effects of lidocaine and quinidine on canine Purkinje fibers at normal pH (7.3) and in the presence of acidosis (pH 6.9). Acidosis alone reduced resting potential, action potential amplitude, and V̇max, while increasing APD90 and conduction time. Lidocaine concentrations of 6x10-6 to 1.5x10-5 M had minimal effect on resting potential, action potential amplitude, and V̇max at pH 7.3. At pH 6.9, the same lidocaine concentrations significantly reduced resting potential (3-10{\%}), action potential amplitude (3-8{\%}) and V̇max (14-22{\%}). Quinidine (6x10-6 to 1.5x10-5 M) reduced resting potential (3-5{\%}), action potential amplitude (4-9{\%}), and V̇max (19-34{\%}) at pH 7.3. At pH 6.9, quinidine produced significantly greater reductions in resting potential (4-15{\%}), action potential amplitude (5-18{\%}), and V̇max (22-49{\%}). These changes were associated with much more quinidine- and lidocaine-induced prolongation of interelectrode conduction time at acidic than at normal pH. Inexcitability occurred at pH 6.9 in 4 of 14 experiments with 1.5x10-5 M quinidine and in 2 of 10 with 1.5x10-5 M lidocaine, and was reversed at the same drug concentration by normalizing pH. Acidosis did not alter the V̇max-resting potential relationship in either the absence or presence of antiarrhythmic agents. Furthermore, changes in ionization did not account for the alterations in electrophysiological effects of quinidine and lidocaine produced by acidosis. Our data suggest that extracellular pH changes may modify importantly the effects of antiarrhythmic agents.",
author = "S. Nattel and V. Elharrar and Zipes, {D. P.} and Bailey, {J. C.}",
year = "1981",
language = "English",
volume = "48",
pages = "55--61",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - pH-dependent electrophysiological effects of quinidine and lidocaine on canine cardiac Purkinje fibers

AU - Nattel, S.

AU - Elharrar, V.

AU - Zipes, D. P.

AU - Bailey, J. C.

PY - 1981

Y1 - 1981

N2 - We used standard microelectrode techniques to evaluate the effects of lidocaine and quinidine on canine Purkinje fibers at normal pH (7.3) and in the presence of acidosis (pH 6.9). Acidosis alone reduced resting potential, action potential amplitude, and V̇max, while increasing APD90 and conduction time. Lidocaine concentrations of 6x10-6 to 1.5x10-5 M had minimal effect on resting potential, action potential amplitude, and V̇max at pH 7.3. At pH 6.9, the same lidocaine concentrations significantly reduced resting potential (3-10%), action potential amplitude (3-8%) and V̇max (14-22%). Quinidine (6x10-6 to 1.5x10-5 M) reduced resting potential (3-5%), action potential amplitude (4-9%), and V̇max (19-34%) at pH 7.3. At pH 6.9, quinidine produced significantly greater reductions in resting potential (4-15%), action potential amplitude (5-18%), and V̇max (22-49%). These changes were associated with much more quinidine- and lidocaine-induced prolongation of interelectrode conduction time at acidic than at normal pH. Inexcitability occurred at pH 6.9 in 4 of 14 experiments with 1.5x10-5 M quinidine and in 2 of 10 with 1.5x10-5 M lidocaine, and was reversed at the same drug concentration by normalizing pH. Acidosis did not alter the V̇max-resting potential relationship in either the absence or presence of antiarrhythmic agents. Furthermore, changes in ionization did not account for the alterations in electrophysiological effects of quinidine and lidocaine produced by acidosis. Our data suggest that extracellular pH changes may modify importantly the effects of antiarrhythmic agents.

AB - We used standard microelectrode techniques to evaluate the effects of lidocaine and quinidine on canine Purkinje fibers at normal pH (7.3) and in the presence of acidosis (pH 6.9). Acidosis alone reduced resting potential, action potential amplitude, and V̇max, while increasing APD90 and conduction time. Lidocaine concentrations of 6x10-6 to 1.5x10-5 M had minimal effect on resting potential, action potential amplitude, and V̇max at pH 7.3. At pH 6.9, the same lidocaine concentrations significantly reduced resting potential (3-10%), action potential amplitude (3-8%) and V̇max (14-22%). Quinidine (6x10-6 to 1.5x10-5 M) reduced resting potential (3-5%), action potential amplitude (4-9%), and V̇max (19-34%) at pH 7.3. At pH 6.9, quinidine produced significantly greater reductions in resting potential (4-15%), action potential amplitude (5-18%), and V̇max (22-49%). These changes were associated with much more quinidine- and lidocaine-induced prolongation of interelectrode conduction time at acidic than at normal pH. Inexcitability occurred at pH 6.9 in 4 of 14 experiments with 1.5x10-5 M quinidine and in 2 of 10 with 1.5x10-5 M lidocaine, and was reversed at the same drug concentration by normalizing pH. Acidosis did not alter the V̇max-resting potential relationship in either the absence or presence of antiarrhythmic agents. Furthermore, changes in ionization did not account for the alterations in electrophysiological effects of quinidine and lidocaine produced by acidosis. Our data suggest that extracellular pH changes may modify importantly the effects of antiarrhythmic agents.

UR - http://www.scopus.com/inward/record.url?scp=0019379965&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019379965&partnerID=8YFLogxK

M3 - Article

VL - 48

SP - 55

EP - 61

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 1

ER -