Propranolol prevents life-threatening arrhythmias in LQT3 transgenic mice: Implications for the clinical management of LQT3 patients☆
| Autor: | Laura Calvillo, Lia Crotti, Eleonora Vullo, Roberto Insolia, Carla Spazzolini, Peter J. Schwartz |
|---|---|
| Přispěvatelé: | Calvillo, L, Spazzolini, C, Vullo, E, Insolia, R, Crotti, L, Schwartz, P |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
WT
wild type LQTS long QT syndrome intraperitoneal Ventricular tachycardia Electrocardiography Mice Cardiac Conduction System Disease BIO/09 - FISIOLOGIA TG transgenic HR heart rate VT ventricular tachycardia LQT3 Transgenic mice WT HR heart rate Sudden death Propranolol ICD implantable cardioverter-defibrillator Long QT Syndrome Treatment Outcome Cardiology LQTS TG ventricular tachycardia wild type VF ventricular fibrillation VPB Cardiology and Cardiovascular Medicine IP intraperitoneal Injections Intraperitoneal medicine.drug medicine.medical_specialty VT Carbachol medicine.drug_class Long QT syndrome ventricular premature beat Adrenergic beta-Antagonists Mice Transgenic VPB ventricular premature beat QT interval Article Long QT syndrome type 3 implantable cardioverter-defibrillator Heart Conduction System Physiology (medical) Internal medicine medicine Animals Humans Beta-blocker Beta blocker transgenic BIO/15 - BIOLOGIA FARMACEUTICA business.industry ICD LQT3 long QT syndrome type 3 MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE ventricular fibrillation medicine.disease Disease Models Animal Death Sudden Cardiac IP Ventricular fibrillation VF business |
| Zdroj: | Heart Rhythm |
| ISSN: | 1556-3871 1547-5271 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|