Do class I antiarrhythmic drugs exert negative inotropic effects via the Na+/Ca2+ exchanger in guinea pig ventricular myocardium?
The negative inotropic effects of class I antiarrhythmic drugs are mediated, at least in part, by Na+/Ca2+ exchanger facilitation secondary to Na+ channel blockade.
Involvement of the Na+/Ca2+ exchanger (NCX) in the negative inotropic effects of class I antiarrhythmic drugs, pilsicainide, cibenzoline, and propafenone, was examined in isolated guinea pig ventricular myocardium. The class I antiarrhythmic drugs, as well as tetrodotoxin, decreased contractile force in a concentration-dependent manner; the magnitude of the effect was propafenone > cibenzoline > pilsicainide. Under conditions of NCX inhibition with the NCX inhibitor SEA0400 or with a low-Na+ extracellular solution, the negative inotropic effects of the class I antiarrhythmic drugs were attenuated. While the effect of pilsicainide was almost abolished, the inhibition was only partial for cibenzoline and propafenone. These results suggest that NCX facilitation secondary to Na+ channel blockade constitutes a common mechanism underlying the negative inotropic effects of class I antiarrhythmic drugs. Drugs with stronger negative inotropic effects have additional mechanisms, and the overall magnitude of negative inotropy is determined by the sum of these actions.
Seki et al. (Wed,) studied this question.