Thèse de doctorat en Sciences biologiques
Sous la direction de Édouard Coraboeuf.
Soutenue en 1989
à Paris 11 .
Acetylcholine (ACH), the parasympathetic nervous system neurotransmitter regulates cardiac activity, and has a slowing effect, through a main action on supra-ventricular structures. The ventricular effects of ACH are less clear. In the first part of this work, cholinomimetic compounds effects on the electrical activity of canine cardiac conducting system are determined. The results show that ACH or carbachol (CCH), lengthen action potential (AP) duration from canine cardiac Purkinje fibers ; the less the external calcium concentration is, the more important are the effects. This unusual CCH-induced lengthening of the AP duration is accompanied by a marked positive inotropic effect. Intracellular calcium movements modifications are presumedly at the onset of the observed phenomena. Cafeine, that is a potent inhibitor of the calcium release from the sarcoplasmic reticulum, antagonizes the CCH induced effects. The electrophysiological effects of CCH on the action potential, could be mediated through a decrease in the potassium background conductance, or an indirect stimulation of the sodium-calcium exchange. The second part of this work is concerned with the determination of the possible cellular origin of cardiac rhythm troubles (with a non muscarinic onset) that are often observed, during an intoxication with anticholinesterase organophosphorous insecticids. The results show that a powerful insecticid, VX (S-(2-diisopropylaminoethyl)-O-ethylmethylphosphonothiolate), has marked effects on the guinea-pig papillary muscle electrical and mecanical activities. These modifications (post-contractions and delayed-after depolarizations, eventualy leading to automatic activity) are not depicted when using CCH or physostigmine instead of VX. They could be explained by a calcium overload of the cardiac cells. An organophosphorous-induced sodium-potassium pump inhibition, could be at the onset of these toxic effects.
Cholinomimetic and anticholinesterase compounds effects on the electrical activity from several cardiac tissues
Détermination des effets de substances cholinomimétriques sur l'activité e��lectrique du tissu conducteur de cœur de chien et des effets d'un puissant insecticide VX sur l'activité électrique et contractile du muscle papillaire de cœur de cobaye.