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


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.


CONCLUSIONS
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.
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Bloco G-CCS, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ 21949-900, Brasil. emedei70@biof.ufrj.br
Emiliano Horacio
EH
Medei
José H M
JH
Nascimento
Roberto C
RC
Pedrosa
Luciane
L
Barcellos
Masako O
MO
Masuda
Serge
S
Sicouri
Marcelo V
MV
Elizari
Antonio C Campos
AC
de Carvalho
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000503:physiopathology; D002908:Chronic Disease; D004562:Electrocardiography; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D008137:Longitudinal Studies; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology / Q000502:physiology*; D012189:Retrospective Studies; D016276:Ventricular Function
D000889:Anti-Arrhythmia Agents; D020746:Calcium Channels, L-Type; D007074:Immunoglobulin G; D015221:Potassium Channels; D018342:Receptors, Adrenergic, beta-1; D001262:Atenolol