The effects of veratridine and BDF 9148 on the action potentials and contractility of the rat right ventricle.
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.
Doggrell
S A
SA
Department of Pharmacology and Clinical Pharmacology, School of Medicine, University of Auckland, New Zealand.
Bishop
B E
BE
Brosch
S
S
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001384:Azetidines / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014701:Veratridine / Q000494:pharmacology*
D001384:Azetidines; D002316:Cardiotonic Agents; C071117:BDF 9148; D014701:Veratridine; D008012:Lidocaine; D007545:Isoproterenol