Antibodies with beta-adrenergic activity from chronic chagasic patients modulate the QT interval and M cell action potential duration

Europace. 2008 Jul;10(7):868-76. doi: 10.1093/europace/eun138. Epub 2008 May 30.

Abstract

Aims: The aim of this study was to investigate whether the sera from chronic chagasic patients (CChPs) with beta-1 adrenergic activity (Ab-beta) can modulate ventricular repolarization. Beta-adrenergic activity has been described in CChP. It increases the L-type calcium current and heart rate in isolated hearts, but its effects on ventricular repolarization has not been described.

Methods and results: In isolated rabbit hearts, under pacing condition, QT interval was measured under Ab-beta perfusion. Beta-adrenergic activity was also tested in guinea pig ventricular M cells. Furthermore, the immunoglobulin fraction (IgG-beta) of the Ab-beta was tested on Ito, ICa, and Iks currents in rat, rabbit, and guinea pig myocytes, respectively. Beta-adrenergic activity shortened the QT interval. This effect was abolished in the presence of propranolol. In addition, sera from CChP without beta-adrenergic activity (Ab-beta) did not modulate QT interval. The M cell action potential duration (APD) was reversibly shortened by Ab-beta. Atenolol inhibited this effect of Ab-beta, and Ab- did not modulate the AP of M cells. Ito was not modulated by isoproterenol nor by IgG-beta. However, IgG-beta increased ICa and IKs.

Conclusion: The shortening of the QT interval and APD in M cells and the increase of IKs and ICa induced by IgG-beta contribute to repolarization changes that may trigger malignant ventricular arrhythmias observed in patients with chronic chagasic or idiopathic cardiomyopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Action Potentials / physiology
  • Animals
  • Anti-Arrhythmia Agents / pharmacology
  • Atenolol / pharmacology
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / physiology
  • Chagas Cardiomyopathy / immunology*
  • Chagas Cardiomyopathy / physiopathology
  • Chronic Disease
  • Electrocardiography*
  • Guinea Pigs
  • Heart / drug effects*
  • Heart / physiology
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Heart Ventricles / drug effects
  • Humans
  • Immunoglobulin G / pharmacology*
  • Longitudinal Studies
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / physiology
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects
  • Potassium Channels / physiology
  • Rabbits
  • Rats
  • Receptors, Adrenergic, beta-1 / immunology
  • Receptors, Adrenergic, beta-1 / physiology*
  • Retrospective Studies
  • Ventricular Function

Substances

  • Anti-Arrhythmia Agents
  • Calcium Channels, L-Type
  • Immunoglobulin G
  • Potassium Channels
  • Receptors, Adrenergic, beta-1
  • Atenolol