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


CONCLUSIONS
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.
Wang
Chuan
C
Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China.
Zhang
Yong-Jian
YJ
Want
Yong-Li
YL
D000818:Animals; D002118:Calcium; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002936:Cinnarizine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D009467:Neuromuscular Depolarizing Agents; D002936:Cinnarizine; D010042:Ouabain; C065758:dipfluzine; D002118:Calcium