1. The effects of
veratridine,
BDF 9148 and
lignocaine on the action potentials and contractile force of the electrically-driven rat right ventricle have been determined. 2.
Veratridine at 10(-7)-10(-6) M and
BDF 9148 at 10(-7)-10(-5) M had no effect on the threshold potential or amplitude but prolonged the ventricular action potentials. 3. In contractility studies,
veratridine at 10(-7)-10(-6) M augmented the cardiac stimulation responses and the augmenting effects with 3 x 10(-7) and 10(-6) M were greater at 2 than 4 Hz. In the presence of
veratridine at 3 x 10(-6) M, the ventricle would not pace. 4.
BDF 9148 at 10(-7)-10(-5) M augmented the cardiac stimulation responses and the augmenting effects with 10(-7) and 3 x 10(-7) M were greater at 2 than 4 Hz and the effect was maximal at 3 x 10(-7) M and submaximal
at 10(-5) M. The effects of
BDF 9148 at 10(-5) were not readily reversible. 5.
Lignocaine at 10(-4) M had no effect on the ventricular action potential duration but decreased the threshold potential and amplitude and also reduced the cardiac stimulation force responses. In the presence of
lignocaine, the augmenting effects of
veratridine and
BDF 9148 on ventricular force were reduced. 6. In summary this study has shown that
BDF 9148 prolongs the action potential and augments the contractile force responses of the rat right ventricle by a
lignocaine-sensitive mechanism.
BDF 9148 or similar drugs may have potential as positive inotropes in the treatment of
heart failure.