Cyclophosphamide effect on ultrastructural myocardial changes in rats on low-magnesium diet.

Intraperitoneal cyclophosphamide administration to a total dose of 225 mg/kg body weight during six weeks produced in rat myocardial fibres evident focal degenerative changes in all organelles, and, fairly frequently, significant damage even up to necrosis. The experiment showed that in rats on low-magnesium diet cyclophosphamide produced more intense and more extensive changes than in rats receiving only cyclophosphamide. The extent of the lesions produced with low and high doses of cyclophosphamide was compared and it was observed that the lesions increased with an enlargement of doses of the drug.

Ultrastructural studies of the myocardium of rats on low-magnesium diet treated with cyclophosphamide.

Cyclophosphamide administration in 20 mg/kg doses intraperitoneally at intervals of 6 days for 6 weeks produced the appearance of slight focal changes in myocardial fibres from the third week on, with dilatation of T-tubules and smooth endoplasmic reticulum channels with electron-dense deposits in them, with the appearance of numerous fat droplets in myocardial fibres, slight mitochondrial changes, with swelling and the appearance of giant or bizarre shaped mitochondria with electron-dense granules and lamellae in them, with numerous lysosomes and some increase in the number of autophagosomes, focal widening of intercalated discs, lysis of myofilaments and myofibrils, cytoplasm swelling, focal necrosis of some myocardial fibres in the 6th week of the experiment, marked swelling of vascular endothelial cells, and a very great rise in the number of collagen fibres. Simultaneous administration of low-magnesium diet and cyclophosphamide caused a greater intensity and an earlier appearance from the 2nd week on, of the disseminated degenerative and necrotic changes in myocardial fibres.

Ultrastructural examinations of rat myocardium on low-magnesium diet during administration of methotrexate.

Methotrexate administration intraperitoneally in doses of 1 mg/kg body weight twice weekly for six weeks produced in the myocardial fibres of these animals slight focal lesions from the third week of the experiment on with the appearance of isolated giant mitochondria of bizarre shapes with electron-dense membranes containing granules, or groups of mitochondria with swollen matrix and disintegration or, partial breakdown of mitochondrial cristae, numerous lysosomes and less numerous autophagosomes, considerable lysis of myofibrils and myofilaments, widening of the tubules of the sarcoplasmic reticulum and T-tubules, presence of few fat droplets, widening of intercalated discs, rarely cytoplasm swelling. From the fifth week on foci of cardiomyocyte fibrosis, in some places swelling of vascular endothelial cells, and a very considerable rise in the number of collagen cells in extracellular spaces. Simultaneous low-magnesium diet and methotrexate caused earlier, from the second week on, and greater intensity of focal necrotic and degenerative changes of cardiomyocytes.

Stress-induced injury of pig myocardium is accompanied by increased lipid peroxidation and depletion of mitochondrial ATP.

The aim of the study was to investigate the mechanisms of myocardial lesions induced by stress in conscious, intact pigs. The animals were subjected to 24 h immobilization, controls were kept in normal conditions. The pigs were killed by electric shock and exsanguination.

Histological and histochemical examinations of myocardium of rats kept on low-magnesium diet and receiving methotrexate.

Methotrexate administration in 1 mg/kg doses intraperitoneally twice weekly for six weeks caused in rat myocardium the following focal, not very intense, histological and histochemical changes from the third week of the experiment on: focal increasing eosinophilia and fuchsinophilia of myocyte cytoplasm, undulating shape of myocardial fibres, contraction nodes, in the sixth week small necrotic foci with associated infiltrations composed of mononuclear cells, presence of p.a.S.

Histological and histochemical examinations of the myocardium of rats kept on low-magnesium diet and treated with cyclophosphamide.

Cyclophosphamide administered intraperitoneally in 20 mg/kg doses at intervals of six days for six weeks caused focal morphological and histochemical lesions of low intensity in rat myocardium. From the third week of the experiment focal eosinophilia and fuchsinophilia of the cytoplasm of a part and later on, of the whole cytoplasm of myocardial fibres, contraction nodes, undulant shape of the fibres, rupture of intercalated discs, very rarely in the sixth week small focal infiltrations composed of mononuclear cells at the site of damaged and disintegrated myocardial fibres, small amount of glycogen, focal increase of acid phosphatase activity and low-grade loss of alkaline phosphatase and magnesium and calcium-dependent ATPases in the sixth week, and unchanged activity of succinic dehydrogenase. Simultaneous use of cyclophosphamide and low-magnesium diet increased the intensity of degenerative changes, which appeared from the second week on, and necrotic changes appearing from the third week on, with more pronounced disturbances in the activity of all studied enzymes, including succinic dehydrogenase, in the sixth week.

Effect of nisoldipine on stress-induced myocardial damage in the conscious pig.

1. The effect of the calcium channel blocker nisoldipine on the myocardial content of lipid peroxidation products (malondialdehyde (MDA), conjugated double bonds (CDB), fluorescent end-products (RF) and mitochondrial adenine nucleotides) was investigated in conscious pigs (n = 14) subjected to 24 h of immobilization stress. Histoenzymatic and electron microscopic studies of the myocardium were also performed.

[Dynamics of lesions to the myocardium in experimental hyper- cholesterolemia].

Dynamics of changes in the myocardium of rabbits subjected to food hypercholesterolemia lasting from 6 to 16 weeks was investigated. An intensification of coronary atheromatosis was proportional to the duration of the high-cholesterol diet. There were observed focal and growing in time damages of cardiomyocytes.

[Selected organopathies caused by experimental magnesium deficiency].

A role of enzyme mediated metabolic processes is discussed. Unfavourable effect of magnesium deficiency on the functioning of various organs may lead to extensive and irreversible morphological changes of focal character. Basing on the results of several experiments and own experience, the author discusses an effect of low-magnesium diet on histological, histochemical, and microscopic lesions to the myocardium, skeletal musculature, liver, and pancreas.