Format

Send to

Choose Destination
See comment in PubMed Commons below
Heart Rhythm. 2014 Jan;11(1):126-32. doi: 10.1016/j.hrthm.2013.10.029. Epub 2013 Oct 14.

Propranolol prevents life-threatening arrhythmias in LQT3 transgenic mice: implications for the clinical management of LQT3 patients.

Author information

1
IRCCS Istituto Auxologico Italiano, Laboratory of Cardiovascular Genetics, Milan, Italy.
2
Fondazione IRCCS Policlinico S. Matteo, Department of Cardiology, Pavia, Italy.
3
Fondazione IRCCS Policlinico S. Matteo, Department of Cardiology, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy.
4
Department of Molecular Medicine, University of Pavia, Pavia, Italy.
5
IRCCS Istituto Auxologico Italiano, Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy; Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
6
IRCCS Istituto Auxologico Italiano, Laboratory of Cardiovascular Genetics, Milan, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy; IRCCS Istituto Auxologico Italiano, Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy; Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town, Cape Town, South Africa; Department of Medicine, University of Stellenbosch, Stellenbosch, South Africa; Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia. Electronic address: peter.schwartz@unipv.it.

Abstract

BACKGROUND:

The efficacy of beta-blockers for treatment of patients with long QT syndrome type 3 (LQT3) has been repeatedly questioned, and it has been suggested that they might be detrimental for this genetic subgroup of patients with long QT syndrome (LQTS). The disquieting consequence has been that cardiologists confronted with LQT3 patients often do not even attempt pharmacologic therapy and implant cardioverter-defibrillators as first-choice treatment. However, the most recent clinical data indicate high efficacy of beta-blocker therapy in LQT3 patients.

OBJECTIVE:

The purpose of this study was to test the antiarrhythmic efficacy of beta-blockers in an established experimental model for LQT3.

METHODS:

After phenotypic validation of 65 ∆KPQ-SCN5A knock-in transgenic (TG) mice compared to 32 wild-type (WT) mice, we tested the effect of the arrhythmogenic cholinergic muscarinic agonist carbachol in 19 WT and 39 TG anesthetized mice, with and without pretreatment with propranolol given intraperitoneally.

RESULTS:

At the same heart rates, TG mice had a markedly longer QT interval than WT mice. Whereas carbachol had minor arrhythmic effects in the WT mice, it produced ventricular tachycardia (VT) and ventricular fibrillation (VF) in 55% of 20 TG mice. By contrast, in none of 19 TG mice pretreated with propranolol did VT/VF occur after carbachol injection.

CONCLUSION:

These experimental data indicate that, contrary to previous reports, beta-blockade effectively prevents VT/VF in a validated LQT3 model. Together with the most recent clinical data, these findings indicate that there is no reason for not initiating protective therapy with beta-blockers in LQT3 patients.

KEYWORDS:

Beta-blocker; HR; ICD; IP; LQT3; LQTS; Long QT syndrome type 3; Sudden death; TG; Transgenic mice; VF; VPB; VT; WT; heart rate; implantable cardioverter-defibrillator; intraperitoneal; long QT syndrome; long QT syndrome type 3; transgenic; ventricular fibrillation; ventricular premature beat; ventricular tachycardia; wild type

PMID:
24135497
PMCID:
PMC3882517
DOI:
10.1016/j.hrthm.2013.10.029
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center