[Effects of combined use of dofetilide and verapamil on the action potential of papillary muscles in guinea pigs].
OBJECTIVE
To test the effects of combined use of dofetilide and verapamil on the action potential of papillary muscles in guinea pigs.


METHODS
Under the stimulation of different frequencies (0.2, 0.5, 1.0, 1.25 or 2.0 Hz), the action potential of papillary muscles in guinea pigs was recorded with the standard microelectrode techniques. The impacts of different concentrations of amiodarone (1, 5 or 10 micromol/L), dofetilide (10, 50, 100 nmol/L), and a combination of 100 nmol/L dofetilide and 1 micromol/L verapamil on the action potential were tested.


RESULTS
Amiodarone prolonged the action potential duration (APD) significantly, measured both at 50% (APD50) and 90% (APD90) of repolarization, in a concentration-dependent manner independent from stimulation frequencies. Dofetilide prolonged APD in a concentration-dependent manner, which was negatively dependent on stimulation frequencies. The frequency-dependent effect was ameliorated by adding 1 micromol/L verapamil to dofetilide.


CONCLUSIONS
Both amiodarone and dofetilide prolong APD in a concentration-dependent manner. The class III antiarrhythmic compounds, amiodarone, has less frequency-dependent effect than the pure class III antiarrhythmic drug. A combined use of potassium and calcium antagonists may reduce the frequency-dependence of the pure class III antiarrhythmic drug.
Li
Miao-Ling
ML
Department of Pharmacology and Biopharmaceutics, West China School of Pharmacy, Sichuan University, Chengdu, China.
Zeng
Xiao-Rong
XR
Yang
Yan
Y
Du
Jun-Rong
JR
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology*; D010627:Phenethylamines / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D010627:Phenethylamines; D026902:Potassium Channel Blockers; D013449:Sulfonamides; D014700:Verapamil; C063533:dofetilide