Related Experiment Videos
Frequency dependent prolongation of effective refractory period by a complex class III antiarrhythmic agent CPU-86017
1Research Division of Pharmacology, Department of Pharmaceutical Chemistry, China Pharmaceutical University, Nanjing 210009, China.
Aim:
To compare the prolongation of the effective refractory period (ERP) of a novel complex Class III agent CPU-86017 with compounds blocking INa (lorcainide, Lor), IK (dofetilide, Dof), ICa (verapamil, Ver) and a complex Class III multiple channel blocking agent (amiodarone, Ami) at different frequency levels.
Methods:
The ERP of the guinea pig right papillary muscle and the anoxic left atrial muscle treated with high K+ at pH 6.6-6.8, in concentrations ranging 0.03-30 micromol/L was compared at frequency levels ranging from 0.5-4.0 Hz.
Results:
CPU-86017 showed a positive frequency dependence (PFD) with respect to ERP in the papillary muscles and a mild reverse frequency dependence (RFD) in the diseased atrium. The potency of ERP prolonging effect of various agents at 4.0 Hz was Dof > CPU-86017 > Ver > Ami > Lor, and Dof > CPU-86017 > Ami > Lor > Ver in the normal papillary and diseased atrial muscle, respectively.
Conclusion:
The profile and potency of prolonging the ERP by CPU-86017 is similar to Dof which blocks IKr in the diseased atrium, and to Ver which blocks ICa in guinea pig ventricle.