Abstract
Pharmacologic action of antiarrhythmic agents in hypoxia was studied with the microelectrode using the guinea pig papillary muscle. Tyrode solution saturated with 95% O2 and 5% CO2 provided normoxic condition and that with 95% N2 and 5% O2 hypoxic condition. The parameters measured were as follows: 1) Vmax: the maximum rate of rise of the action potential, 2) ERP: effective refractory period, 3) ERP/APD90%: the ratio of effective refractory period to action potential duration at 90% repolarization. [1] When the papillary muscle was perfused more than 15 minutes with the hypoxic solution, irreversible changes ensued inevitably. Accordingly, a perfusion with the hypoxic solution for 15 minutes was succeeded by that with the normoxic solution for 30 minutes. This was then followed by another perfusion with the hypoxic solution. [2] Flecainide was examined in 7 cases. The rate of the depression of Vmax by flecainide was significantly (p<0.01) increased in hypoxia (16.3±4.2%) than in normoxia (7.4±2.0%) . There were no significantly differences in the rate of the change of ERP between both conditions. The rate of ERP/APD90% was significandy (p<0.01) increased by flecainide during hypoxia (2.2±0.8%) than during normoxia (0.1±2.1%) . [3] The depression of Vmax and the in crease of ERP/APD90% by flecalnide accurred in a dose-dependent manner in normoxia.
It was concluded that the depression of Vmax by flecainide over the concentration of 2μg/dl were ascribed to its inhibitory effect on the fast Na channel and that its depressive effects were enhanced during hypoxic condition. This inhibitory action was regarded as the main antiarrhythmic action of flecainide.
From the above results, it is expected that flecainide could be effective in the treatment of ventricular arrhythmias in the ischemic heart disease.
