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Biomedical subjects

H G Olbrich

Publications and source records attributed to H G Olbrich.

46 records · Page 3Linked to original sources
PubMed1990

Isolated rat cardiomyocytes as an experimental model for studying acute cardiotoxicity of cyclosporin A.

The acute cardiotoxicity of cyclosporin A was studied in isolated cardiac myocytes from adult rats. In an initial series of 7 animals, myocytes were incubated with concentrations of cyclosporin A ranging from 1 microgram/ml to 50 micrograms/ml. Shape changes of untreated cells, cells treated with cyclosporin A and cells treated with the solvent of cyclosporin A, Tween 80/ethanol, were evaluated. After 8 hours and 16 hours, respectively, of incubation 92 +/- 4.3% and 72 +/- 8.7% of the non-treated control cells were still rod-shaped. Cyclosporin A, however, in a concentration of 5 micrograms/ml decreased the number of rod-shaped cells (79 +/- 3.2% at 8 hours and 51 +/- 3.5% at 16 hours) in comparison to the solvent (94 +/- 3.5% at 8 hours and 76 +/- 5.8% at 16 hours, P less than 0.02). This effect became more pronounced with higher concentrations of cyclosporin A. On the other hand, Tween 80/ethanol alone in higher concentrations also led to a reduced number of rod-shaped cells. In a second series of 7 animals using Tween 80/ethanol and methanol as drug vehicles, myocytes were incubated for 16 hours with 15 micrograms/ml of cyclosporin A in a calcium containing medium (1 mM) or a calcium free medium (10(-4) M ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid). The number of remaining rod-shaped cells was higher in the calcium free medium as opposed to the medium containing calcium when the cells were exposed to cyclosporin A. It is concluded that in the applied model cyclosporin A at high concentrations has an acute cardiotoxic effect which in part appears to be calcium related.

Animals↗
PubMed1990

Calcium overload in human giant cell myocarditis.

Myocardial calcium overload was observed in a patient with giant cell myocarditis. The myocardial calcium content estimated by atomic absorption spectrophotometry amounted to 120 mEq/kg dry weight, and the von Kossa stain disclosed multiple foci with patchy calcifications of myocardial fibres. Cytochemical examination of the ultrastructural calcium localisation using the phosphate-pyroantimonate method showed considerable variation in the subcellular calcium distribution. In normal myocytes calcium precipitates were confined to the inner leaflet of the sarcolemma, T-tubules, intercalated disks, and sporadically to mitochondria. In contrast, extensive calcification of mitochondria and loss of sarcolemmal calcium was evident in necrotic myocytes. A number of grossly normal myocytes also showed an increase of calcium precipitates in slightly swollen mitochondria. These findings suggest that myocardial calcium overload in this case started in viable myocytes and was not merely a secondary phenomenon occurring after cell death.

Calcinosis↗
PubMed1989

[Diastolic ventricular function in hypertrophic, obstructive and non-obstructive cardiomyopathy--effect of gallopamil].

Left ventricular function was investigated by radionuclide ventriculography in 13 patients (11 male, two female) with hypertrophic cardiomyopathy, aged from 22-57 years (mean 45.5 years) at rest and during exercise. Ten patients had hypertrophic obstructive cardiomyopathy with maximal left ventricular outflow tract gradients of 64-290 mmHg (mean 147 mmHg). Left ventricular enddiastolic pressure of all patients ranged from 8-35 mmHg (mean 21 mmHg). Radionuclide ventriculography was performed without therapy, after acute application of a single oral dose of gallopamil (50 mg), and after longterm treatment for 3 weeks (50 mg tid). Ejection fraction at rest after single dose increased from 69.2% to 72.9% (p less than 0.02), peak ejection rate (PER) increased from 333.5 to 362.0/s (p less than 0.01) and peak filling rate (PFR) from 284.5 to 316.5/s (p less than 0.02). Under exercise single dose as well as longterm treatment led to a slight but significant shift in the ratio of PFR/PER (from 1.02 to 1.12 after single dose [p less than 0.04], and to 1.18 with longterm treatment [p less than 0.03]). There was no correlation between the individual response to gallopamil treatment and histopathological parameters such as hypertrophy or fibrosis. These data demonstrate that gallopamil in patients with hypertrophic cardiomyopathy leads to an improvement mainly in left ventricular diastolic function which appears to be most effective under exercise.

Adult↗
PubMed1988

Ultrastructural localization of calcium in the myocardium of cardiomyopathic syrian hamsters.

Cardiomyopathy of the Syrian hamster is characterized by myocardial calcium overload and focal myocardial necrosis. The cause of the myocardial calcium overload is not yet fully understood. In this study, the ultrastructural localization of calcium was determined in normal hamster hearts and in non-necrotic and necrotic myocardium of cardiomyopathic hamsters (strain BIO 82.62). In many cells from the non-necrotic myocardium of the cardiomyopathic hamsters the calcium deposits, visible as 20 nm particles, were confined to the inner leaflet of the plasma membrane, the T-tubules and the intercalated disks. This corresponds to the calcium distribution found in normal hamsters and other mammalian species. A number of morphologically normal cells, however, displayed an increased amount of calcium precipitate in the mitochondria as well as at the sarcolemma indicating that, in the cardiomyopathic hamster, focal calcium overload is detectable cytochemically in cells which otherwise do not show gross abnormalities. In cells showing morphological signs of myolytic degeneration a marked redistribution of calcium precipitate took place. Sarcolemma became devoid of calcium deposits whereas an enormous amount of clustered precipitate occurred in largely swollen mitochondria. These data are in support of a relationship between impaired ion homeostasis and degeneration events in cardiomyopathy. Furthermore, there appears to be a clear parallelism in calcium redistribution between hypoxic and cardiomyopathic myocardium.

Animals↗
PubMed1987

Radionuclide ventriculography: acute and chronic response to verapamil in patients with hypertrophic cardiomyopathy.

Eleven patients with hypertrophic cardiomyopathy were investigated by repeated radionuclide ventriculography. Nine of them were studied for the first time while under long-term treatment for 14 to 84 months. In all eleven patients radionuclide ventriculography was performed after a withdraw of verapamil for at least 14 days or before the onset of therapy respectively (control period). A third investigation was carried out 60 to 90 min after acute administration of 90 mg oral verapamil. A last radionuclide ventriculography was performed following 2 weeks of therapy with 480 mg oral verapamil. After acute administration heart rate significantly increased from 69 +/- 10 to 80 +/- 15/min. EDV was in the normal range. Left ventricular global ejection parameters showed no significant changes except for minimal decrease in ejection time from 309 +/- 29 to 278 +/- 50 ms after acute verapamil administration. The sectorial ejection fraction improved in apical sectors in relation to the basal one, while the global EF remained constant. The ventricular global peak filling rate increased significantly from 283 +/- 61 to 325 +/- 64%/EDV/s after acute administration of verapamil and the sectorial peak filling rate increased in apical sectors compared to basal sectors following acute administration as well as long-term therapy. After withdrawal of verapamil, six out of 11 patients showed a homogeneous left ventricular delay of contraction by means of the Fourier phases which were normalized under short- and long-term verapamil treatment. In conclusion, verapamil caused a marked improvement of the left ventricular contraction delay without significant changes in global systolic function.

Acute Disease↗
PubMed1987

[Muscular obstruction of the right ventricular outflow tract. Subvalvular pulmonary stenosis or hypertrophic cardiomyopathy?].

A case is reported of right ventricular outflow obstruction caused by hypertrophic cardiomyopathy. The pressure gradient between the inflow tract and the outflow tract of the right ventricle was 84 mm Hg. Resection of the hypertrophic muscle bundles practically eliminated the obstruction leaving only an insignificant subvalvular gradient of 2 mm Hg. Histologic examination revealed cardiac muscle cell hypertrophy and disorganization.

Adult↗
PubMed1986

Glutamic acid decarboxylase immunoreactivity in sector CA1 of the human Ammon's horn.

The distribution of glutamic acid decarboxylase (GAD) immunoreactive neurons, fibres and punctae in sector CA 1 of the adult human Ammon's horn was studied in Vibratome sections (40 micron thick) of tissue obtained at surgery and autopsy. On light microscopical examination, the material did not show pathological changes. The antibody was visualized by the unlabelled antibody enzyme method. GAD-immunoreactive neurons, fibres and punctae were present in all layers. Most immunoreactive neurons were located in the stratum pyramidale and stratum lacunosum. Their size ranged from 8 microns in the stratum lacunosum to about 50 microns in the stratum oriens. The somata offered a wide range of shapes, multiform to fusiform with the long axis aligned parallel or vertically to the alveus. All somata belonged to the heterogeneous group of non-pyramidal neurons. The dendrites either radiated in all directions or tended to run in two opposite directions. After bleaching the chromogen and staining for lipofuscin pigment granules and basophilic material, it turned out that within the stratum pyramidale all formerly GAD-immunoreactive neurons belonged to the group of lipofuscin-laden non-pyramidal neurons. Within the other layers, a few formerly GAD-immunoreactive neurons were devoid of lipofuscin pigment. The highest density of GAD-immunoreactive punctae was found in the stratum lacunosum. In addition to numerous GAD-immunoreactive punctae in the pyramidal layer and in the stratum radiatum there were thin GAD-immunoreactive fibres of varying length extending into various directions.

Adult↗
PubMed1985

Ratio of pyramidal cells versus non-pyramidal cells in sector CA1 of the human Ammon's horn.

Combined Golgi/pigment studies revealed that pyramidal neurons and non-pyramidal cells of the Ammon's horn of the human adult can be distinguished from each other by their characteristic lipofuscin pigment deposits. In sector CA1, both the typical pyramidal neurons and the modified forms of pyramidal cells contain a modest amount of fine lipofuscin granules while non-pyramidal cells are either pigment-laden or devoid of lipofuscin deposits. Strips running through the whole depth of the pyramidal cell layer and the stratum oriens of CA1 were examined and all nucleolated nerve cells present within these strips were classified and counted (16 brains, age range from 28 to 69 years). Of the 18,510 neurons classified, 16,765 were pyramidal cells, including their modified versions, and 1,745 were non-pyramidal cells. The pyramidal cells, accordingly, were intermixed with 9.4 +/- 1.0% non-pyramidal neurons. The data presented provide a basis for investigation of the aging and diseased human brain.

Adult↗
PubMedDate not supplied

Cyclosporine increases the intracellular free calcium concentration in electrically paced isolated rat cardiomyocytes.

The effect of cyclosporine on the mean cytoplasmic free calcium concentration in electrically paced single cardiomyocytes from adult rats was studied. Cardiac myocytes were paced by electrical field stimulation with either 2 or 3 Hz in the presence of 5 micrograms/ml cyclosporine or the solvent cremophor. Exposure to cyclosporine during 40 minutes of electrical pacing caused irreversible hypercontracture in most cells, only 22.1% +/- 1.2% (mean +/- SEM) remained rod-shaped versus 64.1% +/- 3.2% in the solvent (p = 0.01). The cytoplasmic free calcium concentration was measured by means of digital image processing of fura-2 fluorescence. Electrical field stimulation increased the cytoplasmic free calcium from 69.7 +/- 5.4 to 124.9 +/- 24.5 nmol/L Ca2+ in the presence of the solvent and from 84.2 +/- 25.4 to 250.1 +/- 55.9 nmol/L in the presence of cyclosporine (p = 0.036 versus solvent). The data provide direct evidence that cyclosporine enhances the cytoplasmic free calcium concentration in single paced rat cardiomyocytes. These findings may be of importance in the consideration of a possible cardiotoxicity of cyclosporine.

Animals↗