Effects of dipfluzine on delayed afterdepolarizations and triggered activity induced by ouabain in guinea pig papillary muscles

Acta Pharmacol Sin. 2002 Oct;23(10):905-9.

Abstract

Aim: To investigate the effects of dipfluzine (Dip) on delayed afterdepolarizations (DADs) and triggered activity (TA) induced by ouabain and high Ca2+ in guinea pig papillary muscles.

Methods: Stable and reproducible DADs and TA in guinea pig papillary muscles were induced by ouabain (1 micromol/L) and high Ca2+ (5.4 mmol/L). DADs and TA were recorded using intracellular glass microelectrode technique.

Results: (1) DADs and TA were markedly inhibited by pretreatment with Dip (10, 30 micromol/L). The amplitude and duration of DADs were reduced by Dip (30 micromol/L) from 10.5 mV +/- 2.2 mV and 230 ms +/- 19 ms to 3.6 mV +/- 0.3 mV and 152 ms +/- 14 ms, respectively, and the induced time of DADs was prolonged from (21+/-5) to (66+/-11) min. TA was not observed. (2) Dip (10, 30 micromol/L) had significant therapeutic effects on DADs and TA. The amplitude and duration of DADs were reduced by Dip (30 micromol/L) from 10.4 mV +/- 1.2 mV and 218 ms +/- 22 ms to 3.3 mV +/- 0.6 mV and 159 ms+/-26 ms. The occurrence of TA was also abolished.

Conclusion: Dip has inhibitory effects on DADs and TA induced by ouabain and high Ca2+ in guinea pig papillary muscles, which might be related to alleviation of intracellular calcium overload through inhibiting calcium channel and/or calcium release from sarcoplasmic reticulum. The effects of Dip on DADs and TA might produce anti-arrhythmic effects.

MeSH terms

  • Animals
  • Calcium
  • Calcium Channel Blockers / pharmacology*
  • Cinnarizine / analogs & derivatives*
  • Cinnarizine / pharmacology*
  • Drug Interactions
  • Female
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Microelectrodes
  • Neuromuscular Depolarizing Agents / pharmacology
  • Ouabain / pharmacology*
  • Papillary Muscles / drug effects*
  • Papillary Muscles / physiology

Substances

  • Calcium Channel Blockers
  • Neuromuscular Depolarizing Agents
  • Cinnarizine
  • Ouabain
  • dipfluzine
  • Calcium