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

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.

• Authors: Laura Calvillo, Carla Spazzolini, Eleonora Vullo, Roberto Insolia, Lia Crotti, Peter J Schwartz
• Journal: Heart rhythm (Heart Rhythm) Vol. 11 Issue 1 Pg. 126-32 (Jan 2014) ISSN: 1556-3871 [Electronic] United States
• PMID: 24135497 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Heart Rhythm Society Published by Heart Rhythm Society All rights reserved.

Chemical References

• Adrenergic beta-Antagonists
• Propranolol

Topics

• Adrenergic beta-Antagonists (administration & dosage)
• Animals
• Cardiac Conduction System Disease
• Death, Sudden, Cardiac (etiology, prevention & control)
• Disease Models, Animal
• Electrocardiography (drug effects)
• Heart Conduction System (drug effects, physiopathology)
• Humans
• Injections, Intraperitoneal
• Long QT Syndrome (complications, drug therapy, physiopathology)
• Mice
• Mice, Transgenic
• Propranolol (administration & dosage)
• Treatment Outcome