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