What question did this study set out to answer?

To determine how the enantiomers [+]-EMD 60263 and [-]-EMD 60264 modulate ventricular membrane currents and to explain why [-]-EMD 60264 lacks positive inotropic activity despite phosphodiesterase inhibition.

February 1, 1999Journal of Cardiovascular Pharmacology

Effects of the Calcium Sensitizer +-EMD 60263 and Its Enantiomer −-EMD 60264 on Cardiac Ionic Currents of Guinea Pig and Rat Ventricular Myocytes

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Population

Isolated guinea pig papillary muscle, guinea pig ventricular myocytes, and rat ventricular myocytes

Design

Preclinical

Authors

HHHerbert M. HimmelBayer (Germany)GAG J AmosInstitut für Medizinische Informatik, Biometrie und Epidemiologie EWErich WettwerWest German Heart and Vascular Center Essen

Discussion

Member takes

Implication

No immediate clinical implications from myocyte data; leaves open how Na+/Ca2+ inhibition balances Ca2+ sensitization versus PDE effects in vivo.

Key Points

To determine how the enantiomers [+]-EMD 60263 and [-]-EMD 60264 modulate ventricular membrane currents and to explain why [-]-EMD 60264 lacks positive inotropic activity despite phosphodiesterase inhibition.
Recorded sodium current (I_Na) and L-type calcium current (I_Ca) in isolated guinea pig ventricular myocytes using the whole-cell voltage-clamp technique.
Measured inward rectifier and transient outward potassium currents in isolated rat ventricular myocytes under voltage-clamp conditions.
Both [+]-EMD 60263 and [-]-EMD 60264 significantly reduced peak I_Na and L-type I_Ca in guinea pig myocytes without shifting voltage-dependent activation or steady-state inactivation curves.
Neither enantiomer affected the inward rectifier or transient outward potassium currents in rat myocytes.

Structured PICO

Population

Isolated guinea pig papillary muscle, guinea pig ventricular myocytes, and rat ventricular myocytes

Intervention

[+]-EMD 60263 and [-]-EMD 60264

Outcome

Effects on membrane currents including sodium current, L-type calcium current, inward rectifier, and transient outward currentsurrogate

The distinct inotropic effects of EMD 60263 enantiomers are explained by the balance between their primary mechanisms (Ca2+ sensitization vs PDE inhibition) and their shared inhibitory effects on Na+ and Ca2+ currents.

Cite This Study

Himmel et al. (1999) studied this question.

synapsesocial.com/papers/6a7e4072fff18652e232f449 https://doi.org/10.1097/00005344-199902000-00019

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Implication

No immediate clinical implications from myocyte data; leaves open how Na+/Ca2+ inhibition balances Ca2+ sensitization versus PDE effects in vivo.

Effects of the Calcium Sensitizer +-EMD 60263 and Its Enantiomer −-EMD 60264 on Cardiac Ionic Currents of Guinea Pig and Rat Ventricular Myocytes

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Effects of the Calcium Sensitizer +-EMD 60263 and Its Enantiomer −-EMD 60264 on Cardiac Ionic Currents of Guinea Pig and Rat Ventricular Myocytes

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider