PubMed HealthSearch

Biomedical subjects

E Carmeliet

Publications and source records attributed to E Carmeliet.

At least 19 recordsLinked to original sources

Comparative effects of lignocaine and lorcainide on conduction in the Langendorff-perfused guinea-pig heart.

The effects of lignocaine and lorcainide on conduction through the AV node and the ventricular conduction system have been investigated in the Langendorff-perfused guinea-pig heart. Basal conduction times were estimated at 80 and 120/min; at each frequency extra-stimuli with variable coupling intervals were applied in order to determine the change in conduction velocity and estimate refractory periods. In most of the preparations paced at 80/min premature impulses were blocked at a site distal to the AV node (distal gate). In therapeutic concentrations (1 to 5 mg . litre-1) and at low frequency of stimulation lignocaine did not change basal conduction times but had a definite slowing effect on the conduction of extra-systoles. Slowing of basal conduction times became prominent at higher frequencies of stimulation or at concentrations above 5 mg . litre-1. In all conditions the effect on the ventricular conduction system was more pronounced than on the AV node. Compared with lignocaine, lorcainide was more effective and more selective. Important changes in basal conduction times and in conduction of premature impulses were observed at 0.31 and 0.63 mg . litre-1. The effect on conduction in the ventricular conduction system was more pronounced than on conduction in the AV node. The dose-effect relationship for different parameters was steeper with lorcainide than with lignocaine. At high concentrations of lorcainide (greater than 1.25 mg . litre-1) intermittent block, especially in the ventricular conduction system, was frequently observed.

Acetamides

Antiarrhythmic, electrophysiologic and hemodynamic effects of lorcainide.

Lorcainide hydrochloride or N-(4-chlorophenyl)-N-[1-(1-methyl-ethyl)-4-piperidinyl]benzeneacetamide mono-hydrochloride (R 15889) is a new anti-arrhythmic drug. Studies in dogs show that lorcainide is effective against post-infarction and ouabain-induced ventricular arrhythmias, and abolishes acetylcholine and aconitine-induced atrial fibrillation; it elevates the threshold of electrically induced ventricular fibrillation. In isolated dog and cow Purkinje fibers, in dog ventricular and in guinea-pig auricular muscle preparations, lorcainide decreases the rate of rise of the transmembrane action potential, the conduction velocity and spontaneous activity. It prolongs the refractory period of isolated Purkpinje and ventricular muscle preparations, and the functional refractory period of the AV node in the guinea-pig heart. It has no effect on Ca mediated electrical activity. Isometric force measurements in isolated cat papillary muscles and hemodynamic studies in anaesthetized and unanaesthetized dogs indicate that lorcainide moderately decreases myocardial contractility. Side effects observed at large doses are of central origin and include salivation, tremor and vomiting. Intravenous injection induces transient peripheral vasodilatation. Lorcainide is an antiarrhythmic of the local anaesthetic type. It is characterized by a good oral absorption, a long duration of action and a large safety factor.

Acetamides

Reduction of potassium permeability by chloride substitution in cardiac cells.

1. The efflux of radioactive K and Cl ions was measured in cow Purkinje fibres and ventricular preparations of cow, cat and frog. The effect of K and Cl was studied by changing the extracellular K concentration between zero and 54 mM, and by substituting Cl ions by acetylglycinate, isethionate, benzenesulphonate, propionate and nitrate. 2. In the absence of Cl the rate coefficient for 42K efflux showed a pronounced fall, which was more pronounced the higher the K concentration. This effect was not related to the change in membrane potential. The rate coefficient for 42K efflux increased in the presence of higher extracellular K concentrations. 3. 36Cl efflux increased in the presence of reduced as well as increased extracellular K concentrations. 4. The calculated permeability coefficient for K (PK) was maximal at 5-4 mM-K, decreased slightly at higher K concentrations, but fell markedly in K-free solutions, (to about 1/5 of the value in 5-4 mM-K). In Cl-free medium PK reduced to 0-67 of the value in the Cl medium, irrespective of the K concentration. 5. The calculated PCl was greater in K-free and 16-2 mM-K than in 5-4 mM-K. 6. The ratio PK/PCl showed important changes as a function of extracellular K concentration: the value was 5 in 5-4 mM-K and fell to 2 and 0-5 respectively in 16-2 and K-free solutions. 7. The results suggest that part of the changes in membrane resistance measured by electrical methods in Cl-free media is due to a simultaneous decrease in K conductance.

Animals

Differential effects of hypoxia with age on the chick embryonic heart. Changes in membrane potential, intracellular K and Na, K efflux and glycogen.

The effects of hypoxia on different parameters of cell membrane function were studied in 7 and 19 day chick embryonic hearts. The following changes were observed: 1. Transmembrane potential: A depolarization of the cell membrane and a decrease in the duration and in the overshoot of the action potential. 2. Intracellular ion concentrations: A decrease in (K)i and an increase in (Na)i. Cellular Ca-content remained constant. 3. K efflux: An increase in the rate coefficient, which was larger in stimulated preparations. These changes were more pronounced in 19 day than in 7 day hearts. The effects of hypoxia were increased by simultaneous substrate depletion and counteracted by an excess external glucose. We conclude that: 1. The 19 day hearts are more sensitive to oxygen lack than the 7 day hearts. The difference can be correlated with the observation that the younger hearts are able to consume more glycogen during hypoxia. 2. The changes of the resting membrane potential and the overshoot of the action potential correlate with changes in respectively (K)i and (Na)i. 3. An increase in the background K current may be an important factor in explaining the shortening of the action potential during hypoxia.

Action Potentials

Hypoxia increases potassium efflux from mammalian myocardium.

Hypoxia with or without simultaneous depletion of extracellular glucose increases 42K-efflux in cat and guinea-pig papillary muscles and bovine Purkinje fibres. The change observed in K efflux may be the result of an increase in K conductance at rest.

Animals

Electrophysiological effects of droperidol in different cardiac tissues.

The effect of droperidol in concentrations between 0.05 and 5 mg/I was evaluated on different electrophysiological variables in auricular preparations of the guinea-pig, papillary muscles of dog and cat, Purkinje fibres of the dog, cow and sheep. At low concentration (0.25 to 0.5mg/I) droperidol decreased pacemaker activity and prolonged the effective refractroy period. The inhibition of pacemaker activity was not accompanied by a reduction in the rate of early diastolic depolarization, but was related to an inhibition of the depolarization process during late diastole. At high concentrations (5mg/I) resting potential, action potential amplitude, (dV/dt)max and conduction velocity were reduced. Reduction of dV/dt during the upstroke was more pronounced at lower membrane potentials, the inactivation curve was shifted to more negative membrane potentials. The action potential was lengthened or shortened, the effect being dependent on the frequency, dose, exposure time and animal species. Droperidol had no deleterious effect on Ca-mediated action potentials. The antiarrhythmic activity of droperidol in therapeutic concentrations (0.25 and 0.5mg/I) can be explained by the reduction of pacemaker activity and the lengthening of the effective refractory period. In terms of changes in ion conductance most effects can be explained by a reduction in Na conductance. No simple explanation can be offered for the complex changes in action potential duration.

Action Potentials

Lidoplazine and Na and K distribution in normo-and hypokalaemic rats.

The effects of lidoplazine on K-metabolism were investigated in two types of experiments. (1) K and Na concentrations were measured in plasma, heart, diaphragm and erythrocytes in normo- and hypokalaemic rats with or without chronic (1 month) lidoplazine treatment. Total body weight, heart weight, dry weight/wet weight ratios and extracellular space were also determined. (2) Radioactive K influx in the heart was measured in acute in vitro experiments with or without lidoplazine. It is demonstrated that while lidoflazine has no effect on the Na and K distribution of normokalaemic animals, it has rather a K-saving effect in conditions of severe loss of intra- and extracellular K-ions. In normal in vitro preparations the unidirectional K-influx is not affected by lidoflazine.

Animals