Positive inotropic effects of RP 62719, a new pure class III antiarrhythmic agent, on guinea pig myocardium. 1992

J P Beregi, and D Escande, and N Coudray, and P Mery, and M Mestre, and D Chemla, and Y Lecarpentier
Institut National de la Santé et de la Recherche Médicale, Unité 275, LOA-ENSTA-Ecole Polytechnique, Palaiseau.

The mechanical effects of RP 62719 [(-)1-[-2-(3,4-dihydro-2H-1- benzopyran-4-yl)ethyl]-4-(3,4-dimethoxyphenyl)-piperidine] were tested in vitro on guinea pig left ventricular papillary muscle. RP 62719 is a novel pure class III antiarrhythmic agent known to prolong the cardiac action potential duration by selectively blocking the inward rectifying K+ current. Mechanical parameters were determined from contraction and relaxation phases under isotonic and isometric conditions. At a concentration of 0.02 microM, RP 62719 did not produce significant effects on inotropy or lusitropy. At 0.2 and 2 microM, the drug improved contraction under both heavy and low loading conditions, as evidenced by a 30% increase in maximum unloaded shortening velocity (Vmax, P < .001), peak amplitude of shortening (delta L, P < .001), peak isometric active force normalized per cross-sectional area (AF/s, P < .001) and positive peak of the force derivative per mm2 (+dF/s, P < .001). At the same concentrations, positive lusitropic effects were evidenced by an increase in maximum lengthening velocity (maxVr) and negative peak of force derivative per mm2 (-dF/s, P < .001). At a higher concentration (20 microM), effects of RP 62719 on inotropy and lusitropy were less marked, thus accounting for the bell-shaped form of the dose-response curve. An increase in the extracellular Ca++ concentration from 2.5 to 3.75 mM improved inotropy to a similar extent (+30-50%) as did 2 microM RP 62719. However, lusitropy and mechanical coupling between contraction and relaxation were not modified in the same proportion under RP 62719 and under 3.75 mM Ca++.(ABSTRACT TRUNCATED AT 250 WORDS)

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
D010880 Piperidines A family of hexahydropyridines.
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002839 Chromans Benzopyrans saturated in the 2 and 3 positions. Dihydrobenzopyrans
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
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000889 Anti-Arrhythmia Agents Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade. Anti-Arrhythmia Agent,Anti-Arrhythmia Drug,Anti-Arrhythmic,Antiarrhythmia Agent,Antiarrhythmia Drug,Antiarrhythmic Drug,Antifibrillatory Agent,Antifibrillatory Agents,Cardiac Depressant,Cardiac Depressants,Myocardial Depressant,Myocardial Depressants,Anti-Arrhythmia Drugs,Anti-Arrhythmics,Antiarrhythmia Agents,Antiarrhythmia Drugs,Antiarrhythmic Drugs,Agent, Anti-Arrhythmia,Agent, Antiarrhythmia,Agent, Antifibrillatory,Agents, Anti-Arrhythmia,Agents, Antiarrhythmia,Agents, Antifibrillatory,Anti Arrhythmia Agent,Anti Arrhythmia Agents,Anti Arrhythmia Drug,Anti Arrhythmia Drugs,Anti Arrhythmic,Anti Arrhythmics,Depressant, Cardiac,Depressant, Myocardial,Depressants, Cardiac,Depressants, Myocardial,Drug, Anti-Arrhythmia,Drug, Antiarrhythmia,Drug, Antiarrhythmic,Drugs, Anti-Arrhythmia,Drugs, Antiarrhythmia,Drugs, Antiarrhythmic
D013268 Stimulation, Chemical The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical. Chemical Stimulation,Chemical Stimulations,Stimulations, Chemical
D015221 Potassium Channels Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits. Ion Channels, Potassium,Ion Channel, Potassium,Potassium Channel,Potassium Ion Channels,Channel, Potassium,Channel, Potassium Ion,Channels, Potassium,Channels, Potassium Ion,Potassium Ion Channel

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