What question did this study set out to answer?

To compare the electrophysiological and inotropic effects of the class III antiarrhythmic agents almokalant (H 234/09), dofetilide (UK-68,798), and E-4031 in vitro.

May 1, 1993Cardiovascular Research

Electrophysiological and inotropic effects of H 234/09 (almokalant) in vitro: a comparison with two other novel IK blocking drugs, UK-68,798 (dofetilide) and E-4031

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Why the study?

Does almokalant have different electrophysiological and inotropic effects compared to dofetilide and E-4031 in isolated rabbit and cat cardiac tissues?

Population

Isolated ventricular muscle and Purkinje fibres of the rabbit; isolated cat papillary muscle

Comparison

H 234/09 (almokalant) vs UK-68,798 (dofetilide) and E-4031

Design

Preclinical

Authors

CAChristina AbrahamssonAstraZeneca (Sweden)GDGöran DukerAstraZeneca (Sweden)CLCharlotte LundbergEricsson (Sweden)

Discussion

Member takes

Implication

Almokalant may confer less dispersion of repolarization than dofetilide or E-4031 in vitro; hypothesis-generating and should not yet change practice.

Key Points

To compare the electrophysiological and inotropic effects of the class III antiarrhythmic agents almokalant (H 234/09), dofetilide (UK-68,798), and E-4031 in vitro.
Recorded transmembrane action potentials in isolated rabbit ventricular muscle and Purkinje fibres.
Assessed contractile force development and refractoriness in isolated cat papillary muscle preparations.
All agents induced concentration-dependent action potential duration prolongation, with almokalant producing significantly less lengthening in Purkinje fibres than dofetilide or E-4031 at matched 15% ventricular prolongation.
All three drugs increased contractile force in cat papillary muscle alongside increases in effective refractory period, with force development plateauing beyond approximately 50% refractoriness prolongation.

Structured PICO

Does almokalant have different electrophysiological and inotropic effects compared to dofetilide and E-4031 in isolated rabbit and cat cardiac tissues?

Population

Isolated ventricular muscle and Purkinje fibres of the rabbit; isolated cat papillary muscle

Intervention

H 234/09 (almokalant)

Comparator

UK-68,798 (dofetilide) and E-4031

Outcome

Electrophysiological effects (action potential duration) and inotropic effects (force development and effective refractory period)surrogate

In vitro, almokalant demonstrated a less unfavorable profile regarding dispersion of repolarization compared to dofetilide and E-4031, while sharing their positive inotropic effects.

Cite This Study

Abrahamsson et al. (1993) studied this question.

synapsesocial.com/papers/6a8157bf080e7f4ac74d6947 https://doi.org/10.1093/cvr/27.5.861

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Implication

Almokalant may confer less dispersion of repolarization than dofetilide or E-4031 in vitro; hypothesis-generating and should not yet change practice.

Electrophysiological and inotropic effects of H 234/09 (almokalant) in vitro: a comparison with two other novel IK blocking drugs, UK-68,798 (dofetilide) and E-4031

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Electrophysiological and inotropic effects of H 234/09 (almokalant) in vitro: a comparison with two other novel IK blocking drugs, UK-68,798 (dofetilide) and E-4031

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider