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 â̂†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.
| Original language | English |
|---|---|
| Pages (from-to) | 126-132 |
| Number of pages | 7 |
| Journal | Heart Rhythm |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2014 |
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Keywords
- Beta-blocker
- Long QT syndrome type 3
- Sudden death
- Transgenic mice
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
Cite this
Propranolol prevents life-threatening arrhythmias in LQT3 transgenic mice : Implications for the clinical management of LQT3 patients. / Calvillo, Laura; Spazzolini, Carla; Vullo, Eleonora; Insolia, Roberto; Crotti, Lia; Schwartz, Peter J.
In: Heart Rhythm, Vol. 11, No. 1, 01.2014, p. 126-132.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Propranolol prevents life-threatening arrhythmias in LQT3 transgenic mice
T2 - Implications for the clinical management of LQT3 patients
AU - Calvillo, Laura
AU - Spazzolini, Carla
AU - Vullo, Eleonora
AU - Insolia, Roberto
AU - Crotti, Lia
AU - Schwartz, Peter J.
PY - 2014/1
Y1 - 2014/1
N2 - 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 â̂†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.
AB - 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 â̂†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.
KW - Beta-blocker
KW - Long QT syndrome type 3
KW - Sudden death
KW - Transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=84891704985&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84891704985&partnerID=8YFLogxK
U2 - 10.1016/j.hrthm.2013.10.029
DO - 10.1016/j.hrthm.2013.10.029
M3 - Article
C2 - 24135497
AN - SCOPUS:84891704985
VL - 11
SP - 126
EP - 132
JO - Heart Rhythm
JF - Heart Rhythm
SN - 1547-5271
IS - 1
ER -