Biochemical, structural and ultrastructural changes in the Prague hereditary hypercholesterolemic (PHHC) rats heart after the long treatment with calcium channel blockers.

Elevated plasma cholesterol concentration may be important in the initiation of heart ischemia and progression of atherogenesis. It has been shown that drugs affecting calcium entry into cells can attenuate the development of this cholesterol induced changes. The aim of this work was to study the influence of five calcium channel blockers 6 weeks treatment on some parameters of lipid metabolism, morphological and ultrastructural changes in the Prague hereditary hypercholesterolemic (PHHC) rats myocardium. The calcium antagonists were administered twice daily perorally in the following doses: nifedipine and nitrendipine 0.2 mg.kg-1, nimodipine 2.5 mg.kg-1, verapamil and diltiazem 1.0 mg.kg-1 body weight. Cholesterol diet decreased the level of free fatty acids significantly (from 5.59 +/- 0.216 to 3.83 +/- 0.371 mumol.g-1), increased the level of total cholesterol (from 28.0 +/- 1.92 to 34.0 +/- 2.90 mumol.g-1) and caused micronecrosis. Examination of myocardial ultrastructure showed a frequent occurrence of lysosomes as well as large numerous autophagic vacuoles and contracture bands of myofibrils. These effects were partly suppressed by calcium channel blockers verapamil and diltiazem, but dihydropyridines were not effective. Observed biochemical changes were in accordance with structural and ultrastructural investigations.

[Quantitative changes in the ultrastructure of myocardial cells in Japanese quail during hypergravity, hypodynamia and space flight]. / Kvantitatívne zmeny ultrastruktúry buniek myokardu japonskej prepelice pocas hypergravitácie, hypodynamie a kozmického letu.

The experimental work aimed at the quantitative ultrastructure of the myocardial cells of the Japanese quail Coturnix coturnix japonica during hypergravitation, hypodynamism and space flight in a Soviet satellite. For the determination of quantitative changes of the myocardial ultrastructure a morphometrical method was used with parameters like the number of mitochondria, average mitochondrial size, relative mitochondrial volume, deficiency of cristae and relative volume of myofibrils. The quails were observed in 3 groups. The absolute control consisted of quails living in normal Earth conditions, in the laboratory group the quails were exposed to conditions of hypergravitation and hypodynamism in a specially constructed centrifuge, and in the flying group the quails were exposed to space flight in a Soviet orbital station MIR. In the group of absolute controls no pathological changes of the myocardial ultrastructure were found. In the flying group there were no significant changes, with the exception of decreased relative volume of myofibrils, which however agrees with the findings on symptoms corresponding to human and animal heart weakness during space flights. In the laboratory group, pathological changes were observed in each of the fractions. The most significant pathological findings were found in the group controls in the center and in hypergravitation combined with hypodynamism. It can be concluded that the laboratories can simulate conditions induced by the start and flight of space ships. (Fig. 2, Ref, 8.)

[Ultrastructure of the myocardium in the calcium channel blocker withdrawal syndrome]. / Syndróm vynechania podávania blokátorov kalciového vstupu v obraze ultrastruktúry myokardu.

Changes in the ultrastructure of rat myocardial cells were investigated after withdrawal of therapy with the calcium entry blockers diltiazem, nifedipine, and verapamil. Two hours after the last administration the ultrastructure was without significant changes in comparison to the control group. However the incidence of contracture bands, dehiscence of intercalated discs and lesions of mitochondria observed 30 hours after therapy withdrawal demonstrated serious damage of myocardial tissue. The recorded changes, practically identical with changes associated with the calcium paradox, were the consequence of withdrawal of calcium entry blocker therapy. The reported morphological changes reflected biochemical and functional changes characteristic of the calcium entry blocker withdrawal syndrome.