Souichiro Sekiya

Classification of antiarrhythmic drugs based on ventricular fibrillation threshold

The antifibrillatory action of antiarrhythmic drugs, classified on the basis of their effects on ventricular fibrillation threshold (VFT), was investigated. The relation between drug action and cardiac excitability, orthodromic/antidromic conduction through Purkinje fibers and ventricular muscle and the restitution of premature action potential duration was studied. Drug classifications were: group A, VFT markedly increased; group B, VFT moderately increased; and group C, no significant change. Group A was subdivided according to presence or absence of the dip phenomenon and supernormal period in the anodal strength-interval curve. Drugs in group A significantly reduced the difference between effective refractory period of orthodromic and antidromic conduction and the range over which the premature action potential duration reappeared. In groups B and C, the effective refractory period in orthodromic conduction was longer than that in controls, and the range of the restitution of premature action potential duration for Purkinje fibers was reduced only slightly.

Evidence that the Na+−Ca2+ exchange system is related to the antiarrhythmic action of disopyramide

1. Disopyramide induced a concentration-dependent decrease in action potential amplitude and Vmax, and prolonged action potential durations (APD50 and APD90) in ventricular muscle. 2. Na+-loaded membrane vesicles isolated from canine ventricular muscle rapidly accumulated Ca2+. 3. Monensin (10(-5) M) abolished Na+-dependent Ca2+ uptake, and Na+ enhanced Ca2+ efflux. 4. Na+-Ca2+ exchange by membrane vesicles was more active in preparations pretreated with disopyramide (10(-5) M) than in control membranes. 5. The results suggest that disopyramide changes Na+ influx from Na+ channel mediated to Na+-Ca2+ exchange mediated. This is verified in part by increased Ca2+ efflux.