Biomaterial Database

Relationship of antiarrhythmic to inotropic activity and antiarrhythmic qualities of the optical isomers of verapamil. 1976

M Raschack

1. The relationship of antiarrhythmic to inotropic activity of the optical isomers of verapamil was studied by comparing their effects on functional refractory period and force of contraction in the isolated left atrium of the guinea pig and on maximum follow frequency and contractility in the dog heart. To evaluate the antiarrhythmic profile of the optical isomers of verapamil the relationship between threshold voltage and impulse duration in the left atrium of the guinea pig and the antagonistic action against ventricular arrhythmias in the rat were studied. 2. (-)Verapamil is nearly 10 times more effective than (+)verapamil in prolonging the functional refractory period in the isolated left atrium of the guinea pig. 3. In the dog heart (-)verapamil is about 8 times more active in reducing a maximum follow frequency at atrial pacing, as well as spontaneous heart rate and in prolonging PQ-duration. 4. In the guinea pig atrium (+)verapamil shows less negative inotropic activity than its enantiomorph. With (+)verapamil the concentration producing a 25% decrease in contractility is 3.7 times higher than that causing a 25% increase in refractory period. With (-)verapamil these concentrations are identical. 5. In the dog i.v. infusion of the isomers, at a dosage inducing identical reduction of maximum follow frequency, is accompanied by a decrease in left ventricular dp/dtmax with (-)verapamil, whereas with the (+)isomer a significant increase of dp/dtmax is observed at a certain dose level. 6. Because of the higher antiarrhythmic activity of (-)verapamil, the antiarrhythmic profile and the inotropic pattern of the racemic compound are mainly due to this isomer. 7. (+)Verapamil shifts the voltage duration curve of the isolated left atrium of the guinea pig to the right and leads to a significant increase in the chronaxie value. (-)Verapamil has no comparable effects on the excitability of the atrial myocardium. 8. In the intact animal (+)verapamil shows additional antiarrhythmic qualities. Like procainamide, but with higher activity, it antagonizes ventricular arrhythmias (ectopic beats, automaticity and flutter or fibrillation) which can be provoked in the rat by i.v. infusion of aconitine. (-)Verapamil and the racemic compound are ineffective against these ventricular rhythm disorders.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009200	Myocardial Contraction	Contractile activity of the MYOCARDIUM.	Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D012032	Refractory Period, Electrophysiological	The period of time following the triggering of an ACTION POTENTIAL when the CELL MEMBRANE has changed to an unexcitable state and is gradually restored to the resting (excitable) state. During the absolute refractory period no other stimulus can trigger a response. This is followed by the relative refractory period during which the cell gradually becomes more excitable and the stronger impulse that is required to illicit a response gradually lessens to that required during the resting state.	Period, Neurologic Refractory,Periods, Neurologic Refractory,Refractory Period, Neurologic,Tetanic Fade,Vvedenskii Inhibition,Wedensky Inhibition,Inhibition, Vvedenskii,Inhibition, Wedensky,Neurologic Refractory Period,Neurologic Refractory Periods,Neuromuscular Fade,Neuromuscular Transmission Fade,Refractory Period, Neurological,Refractory Periods, Neurologic,Electrophysiological Refractory Period,Electrophysiological Refractory Periods,Fade, Neuromuscular,Fade, Neuromuscular Transmission,Fade, Tetanic,Neurological Refractory Period,Neurological Refractory Periods,Refractory Periods, Electrophysiological,Refractory Periods, Neurological,Transmission Fade, Neuromuscular
D002907	Chronaxy	The shortest duration of an electrical stimulus where the threshold amplitude is twice the rheobase - the minimum required for eliciting an ACTION POTENTIAL at any time period. It is a measure of the excitability of nerve or muscle tissue, and is characteristic of types and/or condition of the nerve or muscle cells in the tissue.	Chronaxie
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog
D005260	Female		Females
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006329	Heart Conduction System	An impulse-conducting system composed of modified cardiac muscle, having the power of spontaneous rhythmicity and conduction more highly developed than the rest of the heart.	Conduction System, Heart,Conduction Systems, Heart,Heart Conduction Systems,System, Heart Conduction,Systems, Heart Conduction
D006352	Heart Ventricles	The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.	Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right
D000157	Aconitine	A C19 norditerpenoid alkaloid (DITERPENES) from the root of ACONITUM; DELPHINIUM and larkspurs. It activates VOLTAGE-GATED SODIUM CHANNELS. It has been used to induce ARRHYTHMIAS in experimental animals and it has anti-inflammatory and anti-neuralgic properties.	Acetylbenzoylaconine,Aconitane-3,8,13,14,15-pentol, 20-ethyl-1,6,16-trimethoxy-4-(methoxymethyl)-, 8-acetate 14-benzoate, (1alpha,3alpha,6alpha,14alpha,15alpha,16beta)-,Acetylbenzoyl-aconine,Acetylbenzoyl aconine