What is the clinical evidence from this study?

Study design: Other. Intervention: BRL-32872, azimilide, and E-4031. Primary outcome: Action potential duration (APD).

What question did this study set out to answer?

The aim is to compare the effects of BRL-32872 and azimilide on action potential duration, specifically concerning their channel blocking activities.

January 1, 1998Cardiovascular ResearchOpen Access

Combined potassium and calcium channel antagonistic activities as a basis for neutral frequency dependent increase in action potential duration: comparison between BRL-32872 and azimilide

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Key result

BRL-32872, unlike azimilide, does not induce reverse-rate dependency of action potential prolongation, and reverse-rate dependency induced by E-4031 can be reduced by calcium channel antagonists.

Population

Guinea pig isolated papillary muscles

Comparison

BRL-32872, azimilide, and E-4031 with or without… vs Different basic cycle lengths and…

Design

Preclinical

Authors

ABAntoine BrilServier (France)

Discussion

Member takes

Implication

In vitro data on rate-dependent IKr blockade are hypothesis-generating; leaves open clinical translation to antiarrhythmic efficacy.

Key Points

The aim is to compare the effects of BRL-32872 and azimilide on action potential duration, specifically concerning their channel blocking activities.
Isolated guinea pig papillary muscles were stimulated and superfused with solutions at two different basic cycle lengths (BCL).
Action potential parameters were recorded using standard microelectrode techniques.
E-4031 was administered at varying concentrations with calcium channel antagonists to assess reverse-rate dependence.
Both BRL-32872 and azimilide caused a concentration-dependent increase in action potential duration (APD).
BRL-32872's effect was consistent across stimulation frequencies, while azimilide's effect diminished at shorter BCL.
E-4031 showed a more substantial APD increase at a longer BCL, with reverse-rate dependency impacted by calcium channel antagonists.

Structured PICO

Population

Guinea pig isolated papillary muscles

Intervention

BRL-32872, azimilide, and E-4031 (0.01, 0.03, 0.1 and 0.3 microM) with or without verapamil (0.3 microM), nitrendipine (0.03 microM) or ryanodine (0.1 microM)

Comparator

Different basic cycle lengths (300 and 1000 ms) and presence/absence of calcium channel antagonists

Outcome

Action potential duration (APD) and reverse-rate dependencesurrogate

Compounds with balanced potassium and calcium antagonistic activities, like BRL-32872, may avoid the reverse-rate dependency of action potential prolongation seen with selective potassium channel blockers, potentially reducing proarrhythmic adverse effects.

Cite This Study

Antoine Bril (1998) studied this question. BRL-32872, azimilide, and E-4031 was evaluated on Action potential duration (APD). BRL-32872, unlike azimilide, does not induce reverse-rate dependency of action potential prolongation, and reverse-rate dependency induced by E-4031 can be reduced by calcium channel antagonists.

synapsesocial.com/papers/6a6b00ce78a09e5ab7b39b4f https://doi.org/10.1016/s0008-6363(97)00216-2

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Combined potassium and calcium channel antagonistic activities as a basis for neutral frequency dependent increase in action potential duration: comparison between BRL-32872 and azimilide

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Combined potassium and calcium channel antagonistic activities as a basis for neutral frequency dependent increase in action potential duration: comparison between BRL-32872 and azimilide

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider