What question did this study set out to answer?

To characterize the electrophysiologic properties and evaluate the sinoatrial node selectivity of zatebradine across incremental intravenous doses.

March 1, 2002Journal of Cardiovascular Pharmacology and Therapeutics

Acute Effects of Zatebradine on Cardiac Conduction and Repolarization

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Why the study?

Does zatebradine alter cardiac conduction and repolarization in anesthetized dogs?

Population

15 anesthetized dogs

Comparison

Incremental doses of zatebradine via single i.v… vs Baseline (before zatebradine administration)

Design

Preclinical

Follow-up

15 minutes post-dose

Authors

LSLuyi SenCurtin University GCGuanggen CuiUCLA Medical Center YSYoshiheda SakaguchiUniversity of California, Los Angeles

Discussion

Member takes

Implication

Alerts to conduction effects at higher doses in dogs; leaves open human translation and optimal dosing.

Key Points

To characterize the electrophysiologic properties and evaluate the sinoatrial node selectivity of zatebradine across incremental intravenous doses.
Administered incremental intravenous bolus doses of zatebradine (0.1–1.5 mg/kg) in 15 anesthetized dogs.
Measured electrophysiologic parameters including sinus node recovery time, conduction intervals via His bundle recordings, atrial effective refractory period, and ventricular monophasic action potential duration.
Zatebradine produced peak electrophysiologic effects at 15 minutes (maximum effect at 0.75 mg/kg; IC50 = 0.23 mg/kg) without altering sinus node recovery time, P-wave duration, or PA/HV intervals.
Doses above 0.25 mg/kg significantly lengthened the PR interval and AH interval from 135 to 178 ms (EC50 = 0.58 mg/kg), while leaving the QRS interval unchanged.
Higher doses significantly lengthened QTc from 0.43 to 0.56 s^(1/2) (P < 0.05), ventricular action potential duration at >0.5 mg/kg (EC50 = 0.76 mg/kg), and atrial effective refractory period by 31% (EC50 = 0.69 mg/kg).

Structured PICO

Does zatebradine alter cardiac conduction and repolarization in anesthetized dogs?

Population

15 anesthetized dogs

Intervention

Incremental doses of zatebradine (0.1-1.5 mg/kg) via single i.v. bolus

Comparator

Baseline (before zatebradine administration)

Outcome

Electrophysiologic properties including corrected sinus node recovery time, sinoatrial conduction time, conduction intervals, atrial effective refractory period, and monophasic action potential duration in the ventriclesurrogate

Zatebradine selectively inhibits sinus node automaticity at low doses, but at higher doses, it also inhibits AV nodal conduction and prolongs atrial and ventricular repolarization.

Cite This Study

Sen et al. (2002) studied this question.

synapsesocial.com/papers/6a7e407455c19762e2b29b5c https://doi.org/10.1177/107424840200700i105

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Acute Effects of Zatebradine on Cardiac Conduction and Repolarization

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Acute Effects of Zatebradine on Cardiac Conduction and Repolarization

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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