A model to check the arrhythmogenic activity of antiarrhythmic drugs.
1. In order to evaluate a condition which allows to check arrhythmogenic properties of antiarrhythmic drugs first experiences with the following model are presented. 2. Papillary muscles of guinea pig hearts were exposed to subthreshold concentration of aconitine (8 x 10(-8) M) for 30 min. 3. During the last 10 min of this period a lack of oxygen and glucose was additionally imposed on the muscle. 4. After this priming period, reoxygenation with glucose containing Tyrode solution was introduced and aconitine removed from the organ bath. 5. Restoring the normal conditions, the contractile force and the membrane potential completely recovered. Also the amplitude of the action pontial regained the control value. 6. Only the action potential duration displayed a prolongation of the late repolarization phase which can be described as a hump at a potential of about -55 mV. 7. 30 Minutes after the end of the priming period the muscles were exposed to antiarrhythmic drugs. 8. Quinidine, propafenone and gallopamil (at concentrations reducing the contractile force by 50%) induced a further prolongation of the action potential duration and provoked early after-depolarizations thus acting arrhythmogenic. 9. In contrast, lidocaine and phenytoin did not prolong the action potential duration under this condition and were devoid of any arrhythmogenic activity. 10. The proposed model might offer a possibility to differentiate antiarrhythmic drugs with respect to their unwanted arrhythmogenic activity.
Damarowsky
M
M
Department of Pharmacology, University of Kiel, Germany.
Lüllmann
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D004594:Electrophysiology; D005947:Glucose / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D009200:Myocardial Contraction / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D005947:Glucose; D010100:Oxygen