What question did this study set out to answer?

To investigate the mechanisms and predisposing conditions of drug-induced torsades de pointes using an isolated, perfused rabbit heart model.

September 1, 1998Journal of Cardiovascular Pharmacology

Drug-Related Torsades de Pointes in the Isolated Rabbit Heart

View Full Paper

Ask AI

Bookmark

Why the study?

Does infusion of repolarization-prolonging agents induce torsades de pointes in isolated, perfused rabbit hearts?

Population

Isolated, perfused rabbit hearts (sinus-driven or atrioventricular-blocked)

Design

Preclinical

Authors

LELars EckardtElectrophysiology WHWilhelm HaverkampElectrophysiology HMH. MertensUniversity of Münster

Discussion

Member takes

Implication

Supports the AV-blocked rabbit heart model for torsades research; leaves open translation to clinical arrhythmia risk.

Key Points

To investigate the mechanisms and predisposing conditions of drug-induced torsades de pointes using an isolated, perfused rabbit heart model.
Infused clofilium (1 µM), d,l-sotalol (10 µM), or erythromycin (30–150 µM) into isolated perfused rabbit hearts under normal (5.88 mM) or low (1.5 mM) potassium concentrations.
Evaluated arrhythmias in both sinus-driven and atrioventricular (AV)-blocked heart preparations.
Recorded monophasic action potentials from endocardial and epicardial sites and tested rescue interventions with rapid pacing (<600 ms cycle length) and MgSO4.
Ventricular tachyarrhythmias resembling human torsades de pointes emerged 4 to 12 minutes post-infusion in AV-blocked hearts, presenting as nonsustained episodes that rarely progressed to ventricular fibrillation.
Arrhythmias required both hypokalemia and bradycardia in d,l-sotalol- and erythromycin-treated hearts, whereas bradycardia alone induced arrhythmia with clofilium.
Monophasic action-potential recordings demonstrated early afterdepolarizations in endocardial and epicardial layers, which were suppressed by MgSO4 or pacing at cycle lengths <600 ms.

Structured PICO

Does infusion of repolarization-prolonging agents induce torsades de pointes in isolated, perfused rabbit hearts?

Population

Isolated, perfused rabbit hearts (sinus-driven or atrioventricular-blocked)

Intervention

Infusion of clofilium (1 microM), d,l-sotalol (10 microM), or erythromycin (30-150 microM) in the presence of either normal (5.88 mM) or low (1.5 mM) potassium concentration

Outcome

Development of torsades de pointes (ventricular tachyarrhythmias)surrogate

The isolated AV-blocked rabbit heart serves as a viable experimental model for studying the mechanisms of drug-induced torsades de pointes.

Cite This Study

Eckardt et al. (1998) studied this question.

synapsesocial.com/papers/6a8a96895246293882fd9a63 https://doi.org/10.1097/00005344-199809000-00013

View Full Paper

Ask AI

Bookmark

Drug-Related Torsades de Pointes in the Isolated Rabbit Heart

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Drug-Related Torsades de Pointes in the Isolated Rabbit Heart

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider