[The Ca(2+) sensitizers CGP 48506 and EMD 57033, but not the Na(+) channel modulator BDF 9148, prolong relaxation in isolated cardiomyocytes of the guinea pig]

Z Kardiol. 2001 Apr;90(4):286-91. doi: 10.1007/s003920170175.
[Article in German]

Abstract

The sodium channel modulator DPI 201-106 has been described to posses Ca(2+)-sensitizing properties. Therefore, the present study investigated the inotropic effect of the Na(+)-channel modulator BDF 9148 (1 microM), a congener of DPI 201-106, in comparison with the Ca(2+)-sensitizers CGP 48506 (1-50 mumol/l) and EMD 57033 (1-30 mumol/l) in electrically driven left ventricular cardiomyocytes isolated from guinea pigs. The changes of the contraction amplitude in comparison to the basal cell shortening (cell shortening in micron and %) were continuously recorded with a one-dimensional high speed camera. BDF 9148, CGP 48506, and EMD 57033 exerted a significant increase in the contraction amplitude (p < 0.05 vs. control). The maximal positive inotropic effects of CGP 48506 (50 mumol/l) and EMD 57033 (30 mumol/l) were +249 +/- 30% and +226 +/- 28%, respectively. The corresponding value for BDF 9148 (1 mumol/l) was +176 +/- 16%. However, only the Ca(2+)-sensitizers CGP 48506 and EMD 57033, but not BDF 9148, prolonged the contractile twitch. Especially in patients with an already enhanced intracellular myocardial Ca(2+)-concentration, Ca(2+)-sensitizers, which impair relaxation, may be disadvantageous for therapeutical use despite their positive inotropic effect.

Publication types

  • Comparative Study
  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azetidines / pharmacology*
  • Azocines / pharmacology*
  • Calcium Channels / drug effects*
  • Cardiotonic Agents / pharmacology*
  • Cells, Cultured
  • Diastole / drug effects
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Male
  • Myocardial Contraction / drug effects*
  • Quinolines / pharmacology*
  • Sodium Channels / drug effects*
  • Thiadiazines / pharmacology*

Substances

  • Azetidines
  • Azocines
  • Calcium Channels
  • Cardiotonic Agents
  • Quinolines
  • Sodium Channels
  • Thiadiazines
  • EMD 53998
  • BDF 9148
  • BA 41899