Tedisamil in a chronic canine model of atrial flutter

Peter S. Fischbach, Peter V Johnston, Gregory S. Friedrichs, Benedict R. Lucchesi

Research output: Contribution to journalArticle

Abstract

Tedisamil inhibits several cardiac potassium channels including I(to), I(kr), and the adenosine triphosphate (ATP)sensitive potassium channel (I(KATP)), which may be important in the initiation and maintenance of atrial arrhythmias. We herein report the efficacy of tedisamil in terminating and protecting against the reinduction of atrial flutter (AFL) in a conscious canine model. Sustained AFL (>15 min) was induced in eight of 10 mongrel dogs by programmed atrial stimulation (PAS) 2-41 days after producing a surgical barrier to conduction in the right atrium. At the time of surgery, an epicardial electrode was attached to the right atrial appendage for pacing and recording. Normal saline, 1 ml/kg, was infused after 15 min of AFL as placebo. Tedisamil (1.0 mg/kg) was given intravenously after 30 min of sustained AFL while recording surface ECGs and atrial electrograms. Conversion to sinus rhythm was achieved in 10 of 10 trials (eight dogs) in a mean time of 20.5 s (SD, ± 11.8 s). Tedisamil had a negative chronotropic effect lasting ≥2 h and was protective against the reinduction of AFL. In five dogs, PAS was able to induce AFL in only two of seven trials 2 h after drug infusion. The corrected QT interval (QT(c)) was lengthened for the first 15 min after tedisamil administration (mean, ± 39.3 ms; p <0.05), but thereafter returned to baseline. The QRS interval was not altered by tedisamil. Saline alone, given after 15 min of sustained AFL, converted AFL in one of 11 trials (eight dogs) but did not alter the RR interval, QT(c), or QRS interval compared with values measured during AFL. No significant adverse effects of tedisamil were observed. The results indicate that tedisamil is effective in interrupting and/or preventing reinduction of canine AFL, possibly by prolonging atrial refractoriness through inhibition of one or more potassium ion repolarizing currents in atrial muscle. Further studies are required to address the exact mechanism by which tedisamil exerts its antiarrhythmic effect.

Original languageEnglish (US)
Pages (from-to)212-218
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume34
Issue number2
DOIs
StatePublished - Aug 1999
Externally publishedYes

Fingerprint

Atrial Flutter
Canidae
Dogs
Potassium Channels
tedisamil
Cardiac Electrophysiologic Techniques
Atrial Appendage
Heart Atria
Cardiac Arrhythmias
Potassium
Electrocardiography
Electrodes
Adenosine Triphosphate
Placebos
Maintenance
Ions
Muscles

Keywords

  • ATP-dependent potassium channel
  • Repolarization
  • Supraventricular tachyarrhythmia

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Tedisamil in a chronic canine model of atrial flutter. / Fischbach, Peter S.; Johnston, Peter V; Friedrichs, Gregory S.; Lucchesi, Benedict R.

In: Journal of Cardiovascular Pharmacology, Vol. 34, No. 2, 08.1999, p. 212-218.

Research output: Contribution to journalArticle

Fischbach, Peter S. ; Johnston, Peter V ; Friedrichs, Gregory S. ; Lucchesi, Benedict R. / Tedisamil in a chronic canine model of atrial flutter. In: Journal of Cardiovascular Pharmacology. 1999 ; Vol. 34, No. 2. pp. 212-218.
@article{41319e4928be4b5ba02ebc26e2806550,
title = "Tedisamil in a chronic canine model of atrial flutter",
abstract = "Tedisamil inhibits several cardiac potassium channels including I(to), I(kr), and the adenosine triphosphate (ATP)sensitive potassium channel (I(KATP)), which may be important in the initiation and maintenance of atrial arrhythmias. We herein report the efficacy of tedisamil in terminating and protecting against the reinduction of atrial flutter (AFL) in a conscious canine model. Sustained AFL (>15 min) was induced in eight of 10 mongrel dogs by programmed atrial stimulation (PAS) 2-41 days after producing a surgical barrier to conduction in the right atrium. At the time of surgery, an epicardial electrode was attached to the right atrial appendage for pacing and recording. Normal saline, 1 ml/kg, was infused after 15 min of AFL as placebo. Tedisamil (1.0 mg/kg) was given intravenously after 30 min of sustained AFL while recording surface ECGs and atrial electrograms. Conversion to sinus rhythm was achieved in 10 of 10 trials (eight dogs) in a mean time of 20.5 s (SD, ± 11.8 s). Tedisamil had a negative chronotropic effect lasting ≥2 h and was protective against the reinduction of AFL. In five dogs, PAS was able to induce AFL in only two of seven trials 2 h after drug infusion. The corrected QT interval (QT(c)) was lengthened for the first 15 min after tedisamil administration (mean, ± 39.3 ms; p <0.05), but thereafter returned to baseline. The QRS interval was not altered by tedisamil. Saline alone, given after 15 min of sustained AFL, converted AFL in one of 11 trials (eight dogs) but did not alter the RR interval, QT(c), or QRS interval compared with values measured during AFL. No significant adverse effects of tedisamil were observed. The results indicate that tedisamil is effective in interrupting and/or preventing reinduction of canine AFL, possibly by prolonging atrial refractoriness through inhibition of one or more potassium ion repolarizing currents in atrial muscle. Further studies are required to address the exact mechanism by which tedisamil exerts its antiarrhythmic effect.",
keywords = "ATP-dependent potassium channel, Repolarization, Supraventricular tachyarrhythmia",
author = "Fischbach, {Peter S.} and Johnston, {Peter V} and Friedrichs, {Gregory S.} and Lucchesi, {Benedict R.}",
year = "1999",
month = "8",
doi = "10.1097/00005344-199908000-00006",
language = "English (US)",
volume = "34",
pages = "212--218",
journal = "Journal of Cardiovascular Pharmacology",
issn = "0160-2446",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Tedisamil in a chronic canine model of atrial flutter

AU - Fischbach, Peter S.

AU - Johnston, Peter V

AU - Friedrichs, Gregory S.

AU - Lucchesi, Benedict R.

PY - 1999/8

Y1 - 1999/8

N2 - Tedisamil inhibits several cardiac potassium channels including I(to), I(kr), and the adenosine triphosphate (ATP)sensitive potassium channel (I(KATP)), which may be important in the initiation and maintenance of atrial arrhythmias. We herein report the efficacy of tedisamil in terminating and protecting against the reinduction of atrial flutter (AFL) in a conscious canine model. Sustained AFL (>15 min) was induced in eight of 10 mongrel dogs by programmed atrial stimulation (PAS) 2-41 days after producing a surgical barrier to conduction in the right atrium. At the time of surgery, an epicardial electrode was attached to the right atrial appendage for pacing and recording. Normal saline, 1 ml/kg, was infused after 15 min of AFL as placebo. Tedisamil (1.0 mg/kg) was given intravenously after 30 min of sustained AFL while recording surface ECGs and atrial electrograms. Conversion to sinus rhythm was achieved in 10 of 10 trials (eight dogs) in a mean time of 20.5 s (SD, ± 11.8 s). Tedisamil had a negative chronotropic effect lasting ≥2 h and was protective against the reinduction of AFL. In five dogs, PAS was able to induce AFL in only two of seven trials 2 h after drug infusion. The corrected QT interval (QT(c)) was lengthened for the first 15 min after tedisamil administration (mean, ± 39.3 ms; p <0.05), but thereafter returned to baseline. The QRS interval was not altered by tedisamil. Saline alone, given after 15 min of sustained AFL, converted AFL in one of 11 trials (eight dogs) but did not alter the RR interval, QT(c), or QRS interval compared with values measured during AFL. No significant adverse effects of tedisamil were observed. The results indicate that tedisamil is effective in interrupting and/or preventing reinduction of canine AFL, possibly by prolonging atrial refractoriness through inhibition of one or more potassium ion repolarizing currents in atrial muscle. Further studies are required to address the exact mechanism by which tedisamil exerts its antiarrhythmic effect.

AB - Tedisamil inhibits several cardiac potassium channels including I(to), I(kr), and the adenosine triphosphate (ATP)sensitive potassium channel (I(KATP)), which may be important in the initiation and maintenance of atrial arrhythmias. We herein report the efficacy of tedisamil in terminating and protecting against the reinduction of atrial flutter (AFL) in a conscious canine model. Sustained AFL (>15 min) was induced in eight of 10 mongrel dogs by programmed atrial stimulation (PAS) 2-41 days after producing a surgical barrier to conduction in the right atrium. At the time of surgery, an epicardial electrode was attached to the right atrial appendage for pacing and recording. Normal saline, 1 ml/kg, was infused after 15 min of AFL as placebo. Tedisamil (1.0 mg/kg) was given intravenously after 30 min of sustained AFL while recording surface ECGs and atrial electrograms. Conversion to sinus rhythm was achieved in 10 of 10 trials (eight dogs) in a mean time of 20.5 s (SD, ± 11.8 s). Tedisamil had a negative chronotropic effect lasting ≥2 h and was protective against the reinduction of AFL. In five dogs, PAS was able to induce AFL in only two of seven trials 2 h after drug infusion. The corrected QT interval (QT(c)) was lengthened for the first 15 min after tedisamil administration (mean, ± 39.3 ms; p <0.05), but thereafter returned to baseline. The QRS interval was not altered by tedisamil. Saline alone, given after 15 min of sustained AFL, converted AFL in one of 11 trials (eight dogs) but did not alter the RR interval, QT(c), or QRS interval compared with values measured during AFL. No significant adverse effects of tedisamil were observed. The results indicate that tedisamil is effective in interrupting and/or preventing reinduction of canine AFL, possibly by prolonging atrial refractoriness through inhibition of one or more potassium ion repolarizing currents in atrial muscle. Further studies are required to address the exact mechanism by which tedisamil exerts its antiarrhythmic effect.

KW - ATP-dependent potassium channel

KW - Repolarization

KW - Supraventricular tachyarrhythmia

UR - http://www.scopus.com/inward/record.url?scp=0032788127&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032788127&partnerID=8YFLogxK

U2 - 10.1097/00005344-199908000-00006

DO - 10.1097/00005344-199908000-00006

M3 - Article

C2 - 10445672

AN - SCOPUS:0032788127

VL - 34

SP - 212

EP - 218

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

IS - 2

ER -