Sodium pentobarbital reduces transmural dispersion of repolarization and prevents torsades de Pointes in models of acquired and congenital long QT syndrome

J Cardiovasc Electrophysiol. 1999 Feb;10(2):154-64. doi: 10.1111/j.1540-8167.1999.tb00656.x.


Introduction: Sodium pentobarbital is widely used for anesthesia in experimental studies as well as in clinics, and it is known to prevent the development of torsades de pointes (TdP) in in vivo models of the long QT syndrome (LQTS).

Methods and results: This study examines the effects of pentobarbital on transmural dispersion of repolarization (TDR) and induction of TdP in arterially perfused canine left ventricular wedge preparations in which transmembrane action potentials were simultaneously recorded from epicardial, M, and endocardial regions using floating glass microelectrodes together with a transmural ECG. d-Sotalol and ATX-II were used to mimic the LQT2 and LQT3 forms of congenital LQTS. Both d-sotalol (100 micromol/L, n = 6) and ATX-II (20 nmol/L, n = 6) preferentially prolonged the action potential duration (APD90) of the M cell, thus increasing in the QT interval and TDR, and leading to the development of spontaneous and stimulation-induced TdP. In the absence and presence of d-sotalol, pentobarbital (10, 20, and 50 microg/mL) prolonged the APD90 of epicardial and endocardial cells, and, to a lesser extent, that of the M cell, thus prolonging the QT interval but reducing TDR. In the ATX-II model, the effects of pentobarbital on the QT interval and APD90 were biphasic: 10 microg/mL pentobarbital further prolonged APD90 of epicardial and endocardial cells more than that of the M cell; 20 to 50 microg/mL pentobarbital abbreviated the APD90 of epicardial and endocardial cells less than that of the M cell, thus abbreviating the QT interval and markedly reducing TDR. Twenty to 50 microg/mL pentobarbital totally suppressed spontaneous as well as stimulation-induced TdP in both models

Conclusion: Our data indicate that pentobarbital reduces TDR in control and under conditions of congenital and acquired LQTS, and suggest that this mechanism may contribute to the ability of the anesthetic to prevent the development of spontaneous as well as stimulation-induced TdP under conditions mimicking LQT2, LQT3, and acquired (drug-induced) forms of the LQTS. The data also serve to illustrate that there are circumstances under which QT prolongation may not be arrhythmogenic.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects*
  • Animals
  • Cation Transport Proteins*
  • Disease Models, Animal
  • Dogs
  • Dose-Response Relationship, Drug
  • Electrocardiography / drug effects
  • Electrocardiography / instrumentation
  • Endocardium / drug effects
  • Endocardium / physiopathology
  • Ether-A-Go-Go Potassium Channels
  • Heart Rate / drug effects
  • Heart Ventricles / drug effects
  • Heart Ventricles / pathology
  • Heart Ventricles / physiopathology*
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / therapeutic use*
  • Injections, Intravenous
  • Long QT Syndrome / complications*
  • Long QT Syndrome / congenital
  • Long QT Syndrome / physiopathology
  • Microelectrodes
  • Pentobarbital / administration & dosage
  • Pentobarbital / therapeutic use*
  • Pericardium / drug effects
  • Pericardium / physiopathology
  • Potassium Channels / genetics
  • Potassium Channels, Voltage-Gated*
  • Torsades de Pointes / etiology
  • Torsades de Pointes / physiopathology
  • Torsades de Pointes / prevention & control*


  • Cation Transport Proteins
  • Ether-A-Go-Go Potassium Channels
  • Hypnotics and Sedatives
  • KCNH6 protein, human
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Pentobarbital