PubMed HealthSearch

PubMed · 90549

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

Abstract

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.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

E Carmeliet, M Y Zaman. 1979. Comparative effects of lignocaine and lorcainide on conduction in the Langendorff-perfused guinea-pig heart.. https://doi.org/10.1093/cvr%2F13.8.439

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Degradation of cytochrome P-450 haem by carbon tetrachloride and 2-allyl-2-isopropylacetamide in rat liver in vivo and in vitro. Involvement of non-carbon monoxide-forming mechanisms.

Degradation of intrinsic hepatic [(14)C]haem was analysed as (14)CO formation in living rats and in hepatic microsomal fractions prepared from these animals 16h after pulse-labelling with 5-amino[5-(14)C]laevulinic acid, a precursor that labels bridge carbons of haem in non-erythroid tissues. NADPH-catalysed peroxidation of microsomal lipids in vitro (measured as malondialdehyde) was accompanied by loss of cytochrome P-450 and microsome-associated [(14)C]haem (largely cytochrome P-450 haem), but little (14)CO formation. No additional (14)CO was formed when carbon tetrachloride and 2-allyl-2-isopropylacetamide were added to stimulate lipid peroxidation and increase loss of cytochrome P-450 [(14)C]haem. Because the latter effect persisted despite inhibition of lipid peroxidation with MnCl(2) or phenyl-t-butylnitrone(a spin-trapping agent for free radicals), it was concluded that carbon tetrachloride, as reported for 2-allyl-2-isopropylacetamide, may promote loss of cytochrome P-450 haem through a non-CO-forming mechanism independent of lipid peroxidation. By comparison with breakdown of intrinsic haem, catabolism of [(14)C]methaemalbumin by microsomal haem oxygenase in vitro produced equimolar quantities of (14)CO and bilirubin, although these catabolites reflected only 18% of the degraded [(14)C]haem. This value was increased to 100% by addition of MnCl(2), which suggests that lipid peroxidation may be involved in degradation of exogenous haem to products other than CO. Phenyl-t-butylnitrone completely blocked haem oxygenase activity, which suggests that hydroxy free radicals may represent a species of active oxygen used by this enzyme system. After administration of carbon tetrachloride or 2-allyl-2-isopropylacetamide to labelled rats, hepatic [(14)C]haem was decreased and haem oxygenase activity was unchanged; however, (14)CO excretion was either unchanged (carbon tetrachloride) or decreased (2-allyl-2-isopropylacetamide). These changes were unaffected by cycloheximide pretreatment. From the lack of parallel losses of cytochrome P-450 [(14)C]haem and (14)CO excretion, one may infer that an important fraction of hepatic [(14)C]haem in normal rats is degraded by endogenous pathways not involving CO. We conclude that carbon tetrachloride and 2-allyl-2-isopropylacetamide accelerate catabolism of cytochrome P-450 haem through mechanisms that do not yield CO as an end product, and that are insensitive to cycloheximide and independent of haem oxygenase activity.

Acetamides

Studies on the mechanism of action of hexamethylene bisacetamide, a potent inducer of erythroleukemic differentiation.

Hexamethylene bisacetamide (diacetyldiamino hexane) is a potent inducer of erythroid differentiation in murine erythroleukemia cells. Hexamethylene bisacetamide and the closely related pentamethylene bisacetamide were synthesized with radioactive labels in various portions of the molecule and the uptake, metabolism, and intracellular distribution determined. Bisacetamides are taken up by the cell; an intracellular concentration equal to the extracellular concentration is achieved by 6-8 h. Commitment to differentiation is not detected until at least 10 h after equilibration. Both uptake and commitment to differentiate are concentration and temperature dependent. The majority of the compound is deacetylated upon cell entry and the acetate portion incorporated nonspecifically into lipid and protein. Acetate competes with the incorporation of hexamethylene bisacetamide into protein and lipid, but does not affect inducing activity. The diamine portion of the molecule is detected only in the cytoplasm, in a trichloroacetic acid-soluble and acetylated form, whereas the acetate moiety is detected in both cytoplasm and nucleus and in both a trichloroacetic acid-soluble and insoluble form. The cellular uptake of diamines and bisacetamides (acetylated diamines) are similar, but acetylation of the diamine greatly increases inducing activity.

Acetamides