β-Adrenergic blocking property of dl-sotalol maintains class III efficacy in guinea pig ventricular muscle after isoproterenol

William J. Groh, Kevin J. Gibson, John H. McAnulty, James Maylie

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: Catecholamines antagonize the efficacy of several class III antiarrhythmic agents. To determine the role of the intrinsic β-adrenergic blocking property of dl-sotalol in maintaining class III efficacy during a high-catecholamine state, we compared the electrophysiological properties of dl-sotalol with those of d-sotalol, which is devoid of significant β- adrenergic blocking effect, before and after isoproterenol infusion. Methods and Results: Action potential duration at 90% repolarization (APD90) was prolonged in isolated guinea pig papillary muscles perfused with d-sotalol and dl-sotalol 10-4 mol/L over stimulation cycle lengths from 200 to 2000 ms. The increases in APD90 for d-sotalol and dl-sotalol over control were 10.9±2.5 to 23.7±4.8 ms and 27.9±4.0 to 39.0±5.6 ms, respectively. APD90 shortened to less than control in papillary muscles treated with d- sotalol but not dl-sotalol on addition of isoproterenol 10-6 mol/L: - 31.2±3.5 to -18.3±4.8 ms and 10.5±3.6 to 33.3±7.8 ms, respectively, P2+ channel block and Na+ channel inactivation. I(out), I(tail), and I(tot) were reduced in myocytes perfused with d-sotalol and dl-sotalol 10-4 mol/L: I(out), 36.1±4.1%, -40.5±3.3%; I(tail), -59.3±4.6%, -62.2±11.1%; I(tot), -27.3±4.3%, -50.0±11.8%. I(out) and I(tot) increased to a greater degree in myocytes treated with d-sotalol than dl-sotalol on addition of isoproterenol 10-6 mol/L: I(out), 100.3±20.6%, 11.3±7.6%, P=.002; I(tot), 86.8±39.2%, -41.1±20.9%, P=.01. I(tail) tended to increase more in myocytes treated with d-sotalol than dl- sotalol on addition of isoproterenol, but the difference was not significant (-9.1±13.5%, -28.0±9.0%). Conclusions: The β-adrenergic blocking property of dl-sotalol maintains APD prolongation and repolarizing outward current block during isoproterenol infusion in guinea pig ventricular muscle. Extrapolation of these data to a clinical setting may explain the efficacy of dl-sotalol in diminishing ventricular arrhythmia recurrence.

Original languageEnglish (US)
Pages (from-to)262-264
Number of pages3
JournalCirculation
Volume91
Issue number2
StatePublished - Jan 15 1995

Fingerprint

Sotalol
Isoproterenol
Adrenergic Agents
Guinea Pigs
Muscles
Muscle Cells
Action Potentials
Tail
pamidronate
Papillary Muscles
Catecholamines

Keywords

  • agents
  • antiarrhythmia
  • catecholamines
  • potassium

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

β-Adrenergic blocking property of dl-sotalol maintains class III efficacy in guinea pig ventricular muscle after isoproterenol. / Groh, William J.; Gibson, Kevin J.; McAnulty, John H.; Maylie, James.

In: Circulation, Vol. 91, No. 2, 15.01.1995, p. 262-264.

Research output: Contribution to journalArticle

@article{06bb98920bdd4ae490e03b9e46ddcbcd,
title = "β-Adrenergic blocking property of dl-sotalol maintains class III efficacy in guinea pig ventricular muscle after isoproterenol",
abstract = "Background: Catecholamines antagonize the efficacy of several class III antiarrhythmic agents. To determine the role of the intrinsic β-adrenergic blocking property of dl-sotalol in maintaining class III efficacy during a high-catecholamine state, we compared the electrophysiological properties of dl-sotalol with those of d-sotalol, which is devoid of significant β- adrenergic blocking effect, before and after isoproterenol infusion. Methods and Results: Action potential duration at 90{\%} repolarization (APD90) was prolonged in isolated guinea pig papillary muscles perfused with d-sotalol and dl-sotalol 10-4 mol/L over stimulation cycle lengths from 200 to 2000 ms. The increases in APD90 for d-sotalol and dl-sotalol over control were 10.9±2.5 to 23.7±4.8 ms and 27.9±4.0 to 39.0±5.6 ms, respectively. APD90 shortened to less than control in papillary muscles treated with d- sotalol but not dl-sotalol on addition of isoproterenol 10-6 mol/L: - 31.2±3.5 to -18.3±4.8 ms and 10.5±3.6 to 33.3±7.8 ms, respectively, P2+ channel block and Na+ channel inactivation. I(out), I(tail), and I(tot) were reduced in myocytes perfused with d-sotalol and dl-sotalol 10-4 mol/L: I(out), 36.1±4.1{\%}, -40.5±3.3{\%}; I(tail), -59.3±4.6{\%}, -62.2±11.1{\%}; I(tot), -27.3±4.3{\%}, -50.0±11.8{\%}. I(out) and I(tot) increased to a greater degree in myocytes treated with d-sotalol than dl-sotalol on addition of isoproterenol 10-6 mol/L: I(out), 100.3±20.6{\%}, 11.3±7.6{\%}, P=.002; I(tot), 86.8±39.2{\%}, -41.1±20.9{\%}, P=.01. I(tail) tended to increase more in myocytes treated with d-sotalol than dl- sotalol on addition of isoproterenol, but the difference was not significant (-9.1±13.5{\%}, -28.0±9.0{\%}). Conclusions: The β-adrenergic blocking property of dl-sotalol maintains APD prolongation and repolarizing outward current block during isoproterenol infusion in guinea pig ventricular muscle. Extrapolation of these data to a clinical setting may explain the efficacy of dl-sotalol in diminishing ventricular arrhythmia recurrence.",
keywords = "agents, antiarrhythmia, catecholamines, potassium",
author = "Groh, {William J.} and Gibson, {Kevin J.} and McAnulty, {John H.} and James Maylie",
year = "1995",
month = "1",
day = "15",
language = "English (US)",
volume = "91",
pages = "262--264",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - β-Adrenergic blocking property of dl-sotalol maintains class III efficacy in guinea pig ventricular muscle after isoproterenol

AU - Groh, William J.

AU - Gibson, Kevin J.

AU - McAnulty, John H.

AU - Maylie, James

PY - 1995/1/15

Y1 - 1995/1/15

N2 - Background: Catecholamines antagonize the efficacy of several class III antiarrhythmic agents. To determine the role of the intrinsic β-adrenergic blocking property of dl-sotalol in maintaining class III efficacy during a high-catecholamine state, we compared the electrophysiological properties of dl-sotalol with those of d-sotalol, which is devoid of significant β- adrenergic blocking effect, before and after isoproterenol infusion. Methods and Results: Action potential duration at 90% repolarization (APD90) was prolonged in isolated guinea pig papillary muscles perfused with d-sotalol and dl-sotalol 10-4 mol/L over stimulation cycle lengths from 200 to 2000 ms. The increases in APD90 for d-sotalol and dl-sotalol over control were 10.9±2.5 to 23.7±4.8 ms and 27.9±4.0 to 39.0±5.6 ms, respectively. APD90 shortened to less than control in papillary muscles treated with d- sotalol but not dl-sotalol on addition of isoproterenol 10-6 mol/L: - 31.2±3.5 to -18.3±4.8 ms and 10.5±3.6 to 33.3±7.8 ms, respectively, P2+ channel block and Na+ channel inactivation. I(out), I(tail), and I(tot) were reduced in myocytes perfused with d-sotalol and dl-sotalol 10-4 mol/L: I(out), 36.1±4.1%, -40.5±3.3%; I(tail), -59.3±4.6%, -62.2±11.1%; I(tot), -27.3±4.3%, -50.0±11.8%. I(out) and I(tot) increased to a greater degree in myocytes treated with d-sotalol than dl-sotalol on addition of isoproterenol 10-6 mol/L: I(out), 100.3±20.6%, 11.3±7.6%, P=.002; I(tot), 86.8±39.2%, -41.1±20.9%, P=.01. I(tail) tended to increase more in myocytes treated with d-sotalol than dl- sotalol on addition of isoproterenol, but the difference was not significant (-9.1±13.5%, -28.0±9.0%). Conclusions: The β-adrenergic blocking property of dl-sotalol maintains APD prolongation and repolarizing outward current block during isoproterenol infusion in guinea pig ventricular muscle. Extrapolation of these data to a clinical setting may explain the efficacy of dl-sotalol in diminishing ventricular arrhythmia recurrence.

AB - Background: Catecholamines antagonize the efficacy of several class III antiarrhythmic agents. To determine the role of the intrinsic β-adrenergic blocking property of dl-sotalol in maintaining class III efficacy during a high-catecholamine state, we compared the electrophysiological properties of dl-sotalol with those of d-sotalol, which is devoid of significant β- adrenergic blocking effect, before and after isoproterenol infusion. Methods and Results: Action potential duration at 90% repolarization (APD90) was prolonged in isolated guinea pig papillary muscles perfused with d-sotalol and dl-sotalol 10-4 mol/L over stimulation cycle lengths from 200 to 2000 ms. The increases in APD90 for d-sotalol and dl-sotalol over control were 10.9±2.5 to 23.7±4.8 ms and 27.9±4.0 to 39.0±5.6 ms, respectively. APD90 shortened to less than control in papillary muscles treated with d- sotalol but not dl-sotalol on addition of isoproterenol 10-6 mol/L: - 31.2±3.5 to -18.3±4.8 ms and 10.5±3.6 to 33.3±7.8 ms, respectively, P2+ channel block and Na+ channel inactivation. I(out), I(tail), and I(tot) were reduced in myocytes perfused with d-sotalol and dl-sotalol 10-4 mol/L: I(out), 36.1±4.1%, -40.5±3.3%; I(tail), -59.3±4.6%, -62.2±11.1%; I(tot), -27.3±4.3%, -50.0±11.8%. I(out) and I(tot) increased to a greater degree in myocytes treated with d-sotalol than dl-sotalol on addition of isoproterenol 10-6 mol/L: I(out), 100.3±20.6%, 11.3±7.6%, P=.002; I(tot), 86.8±39.2%, -41.1±20.9%, P=.01. I(tail) tended to increase more in myocytes treated with d-sotalol than dl- sotalol on addition of isoproterenol, but the difference was not significant (-9.1±13.5%, -28.0±9.0%). Conclusions: The β-adrenergic blocking property of dl-sotalol maintains APD prolongation and repolarizing outward current block during isoproterenol infusion in guinea pig ventricular muscle. Extrapolation of these data to a clinical setting may explain the efficacy of dl-sotalol in diminishing ventricular arrhythmia recurrence.

KW - agents

KW - antiarrhythmia

KW - catecholamines

KW - potassium

UR - http://www.scopus.com/inward/record.url?scp=0028876844&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028876844&partnerID=8YFLogxK

M3 - Article

C2 - 7805226

AN - SCOPUS:0028876844

VL - 91

SP - 262

EP - 264

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 2

ER -