[Comparison of the effect of nifedipine and verapamil on lipid metabolism in experimental atherosclerosis in rabbits]. / Porovnanie vplyvu nifedipínu a verapamilu na metabolizmus lipidov pocas experimentálnej aterosklerózy u králikov.

The aim of the work was to study the effect of 8-week treatment with two calcium channel blockers on some parameters of lipid metabolism in rabbits. Experimental atherosclerosis was induced by 1% cholesterol diet. The calcium channel blockers were administered twice daily in the following doses: nifedipine 1.0 mg.kg-1 and verapamil 2.0 mg/kg-1 x day-1. The treatment with calcium channel blockers enhanced the level of total cholesterol as well as of triglycerides and decreased the HDL: total cholesterol ratio in all the experimental groups. The changes induced by nifedipine were, however, less significant compared to the effect of verapamil. The absolute amount of fatty acids determined by gas chromatography was lower after nifedipine administration in comparison to the verapamil treated group. Nifedipine induced a more favorable proportion in the composition of fatty acids. The increase in the level of monounsaturated fatty acids (palmitoleic and oleic acid) as well as the decrease in the level of polyunsaturated fatty acids (especially linoleic acid) was the lowest in the nifedipine treated group. (Fig. 6, Ref. 30.).

Antiarrhythmic activity of heptacaine and some of its derivatives.

In the evaluation of experimental antiarrhythmic effect in guinea pigs, by a method of antagonizing ouabain arrhythmogenity, there was found a maximum effect of N-[2-(2-heptyloxy-phenylcarbamoyloxy)-ethyl]-piperidinium-chloride (heptacaine). The shortening or prolongation of the alkoxy substitution in the ortho-position, or the shift of hexyloxy substitution to the meta- or para-position, respectively, causes a decrease in activity. Negative chronotropic effect of heptacaine is increased and prolonged during the 5th min after acute i.v. application. The effect of lidocaine was short-lasting and decreased. In antagonizing experimental adrenaline (epinephrine) arrhythmogenity, heptacaine showed an important antiarrhythmic effect, too. In the relative hypotensive activity evaluation, there was an important effect in the 1st min after i.v. application and this decreased to the same values as those of lidocaine in the 5th min. Hypotensive effect evaluation of lidocaine and heptacaine after higher doses than therapeutic ones showed that the hypotensive effect of heptacaine takes place at the same rate as that of lidocaine and by the 10th min reaches control values. Values of experimental partition coefficient showed an increase in relation to prolongation of ortho-alkoxy substitution in the sequence: propoxy less than pentyloxy less than heptyloxy less than nonyloxy. Submaximal value by the heptacaine may reflect an optimal hydrophylic-lipophylic balance of its molecule. But in the evaluation on antiouabain effect and partition coefficient, there is no simple direct correlation in structure-activity relationship.

[The effect of stress factors on the ultrastructure of the myocardium and creatinine kinase activity in the blood of rats premedicated with metipranolol]. / Vplyv stresových faktorov na ultrastruktúru myokardu a aktivitu sérovej kreatinkinázy u potkanov premedikovaných metipranololom.

After a four-hour long immobilization stress, heart muscle cells, viewed in the electron microscope, showed a fine swelling of the endothelium of the capillaries, a fine dilatation of the sarcoplasmatic reticulum, but formation of fat drops was rare. Following sudden withdrawal of the application of metipronolol stress caused more serious damage to the ultrastructure of the heart muscle cells than if the animals were subjected to stress alone. The authors observed large accumulations of fat droplets, dilatation of the sarcoplasmatic reticulum, swollen mitochondria and spindle shaped dehiscences in the intercalated discs. Immobilization stress led to increased activity of creatine kinase in the serum, while previous application of metipranolol caused its decrease.

The metabolic and structural changes of the liver in experimental animals after administration of isoprenaline.

Application to rats and rabbits of higher doses of isoprenaline (IP) results in derangement of glycid metabolism, manifested by the decrease of free glycogen (free-GL), and in an even more significant impairment of lipid metabolism, evidenced by an earlier increase of non-esterified fatty acids (NEFA) followed by an increase of esterified fatty acids (EFA) and a concomitant development of fatty infiltration, all indicators of marked lipomobilization. Histograms obtained from hypersensitive individuals show besides fatty infiltrations also necrobiotic processes and structural changes, seen as distinctly marked liver cell membranes. It is perhaps relevant to draw attention to the fact that there are both individual and species differences in the metabolic changes ensuing on application of IP.