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Biomedical subjects

A M Gerdes

Publications and source records attributed to A M Gerdes.

At least 91 records · Page 5Linked to original sources
PubMed1988

Regional changes in myocyte size during the reversal of thyroid-induced cardiac hypertrophy.

Regional changes in cardiac myocyte size resulting from thyroid treatment, and the subsequent reversal of hypertrophy following removal of the thyrotoxic stimulus, were examined. Isolated myocytes were prepared from weight-matched controls and rats treated with desiccated thyroid hormone for 10 weeks. Cells were collected from the right and left ventricles. Cell volume was determined with a Coulter Channelyzer system. Cell length was measured directly using a phase microscope. Myocyte cross-sectional area was calculated from cell volume/length. After 10 weeks thyroid treatment, cell volume was increased in all regions, especially the right ventricle and the epimyocardium of the left ventricle (P less than 0.01). Although cell length was increased in all regions (N.S.), most of the myocyte hypertrophy was due to an increase in cross-sectional area, especially in the right ventricle (P less than 0.01) and epimyocardium of the left ventricle (N.S.). By 2 weeks post-treatment, a substantial regression of myocyte hypertrophy had occurred. However, heart weight was still significantly larger than control (P less than 0.001), due to an incomplete regression of myocyte volume. This study indicates that thyroid hormones stimulate myocyte hypertrophy by increasing both cross-sectional area and cell length. The response is more pronounced in right ventricles than in left ventricles. Within the left ventricle, epimyocardial cells enlarge the most. At 2 weeks post-treatment, cardiac hypertrophy is still present and myocytes have not completely returned to a normal size.

Animals↗
PubMed1988

Structural remodeling of cardiac myocytes in rats with arteriovenous fistulas.

Structural changes in the heart associated with chronic volume overloading have not been adequately documented. In anesthetized adult rats, microsurgical techniques were used to produce two types of arteriovenous shunts. The end of a femoral artery was connected to the side of a femoral vein to produce a femoral shunt. Aortocaval fistulas were produced by placing a venous graft (femoral vein) between the abdominal aorta and inferior vena cava. A polyethylene ring was placed around the venous graft to control the size of the shunt. After 10 weeks, rats were anesthetized and hearts were excised, weighed, and perfused with collagenase to obtain isolated myocytes. Heart weight/body weight of rats increased 15% (p less than 0.005) with unilateral femoral fistulas and 41% (p less than 0.001) with aortocaval fistulas. Length of isolated cardiac myocytes was measured directly with a microscope. Cell volume was measured with a Coulter Channelyzer. Myocyte cross-sectional area was calculated from cell volume/cell length. Cell volume increased in proportion to heart weight in each experimental model. With both types of shunts, the majority of myocyte hypertrophy was due to an increase in cell length. There was a trend toward an increase in cross-sectional area in each region of both fistula groups, although this change was not statistically significant. These results indicate that eccentric cardiac hypertrophy was associated with enlargement of individual myocytes primarily as a result of increased length.

Animals↗
PubMed1987

Comparison of regional differences in cardiac myocyte dimensions in rats, hamsters, and guinea pigs.

Isolated myocytes were prepared from Sprague Dawley rats, golden Syrian hamsters, and Hartley guinea pigs to investigate regional variations in myocyte size. Cell volume (V) was measured with a Coulter Channelyzer, cell length (L) was measured directly, and cross-sectional area (CSA) was calculated from V/L. Compared to values from the left ventricle (LV), right ventricular L was shorter in the rat (P less than .01) and hamster (P less than .05) and longer in the guinea pig (P less than .01). Guinea pig atrial L was shorter (P less than .01) than L in the right ventricle (RV) but did not differ from L in the LV. No significant differences in L existed between endomyocardium, middle myocardium, and epimyocardium of the LV in all three species. In rats and hamsters, myocytes from the RV had smaller V and CSA values (P less than .01) compared to any region of the LV. A transmural gradient of cellular dimensions existed in the LV of the rat, but not in hamster, with V and CSA of endomyocardium being largest and epimyocardium smallest (P less than .01). Endomyocardial V and CSA were larger (P less than .01) than all other regions in the hamster, but the difference was not significant compared to epimyocardial V. In the guinea pig, no significant differences in V existed between RV and LV or between the three LV regions. No pattern of regional differences was seen between ventricular CSA values in the guinea pig. Guinea pig atrial V and CSA values were smaller (P less than .01) than those for ventricular myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Experience with first trimester prenatal diagnosis of Menkes disease.

We have performed 28 first trimester diagnoses for Menkes disease in 27 high risk pregnancies by direct copper measurement on chorionic villi (c.v.) Two male fetuses were found to be affected because of significantly increased copper content. In one male fetus a slightly increased copper content was observed indicating an exogenous copper contamination of the sample. This view was supported by normal results observed after abortion. Three out of 15 diagnostic c.v. samples with a female karyotype showed increased copper levels. In two of these cases, part of the copper content might have been released from the cannulae used for these particular biopsies. Histochemical visualization of copper accumulation in fixed chorionic villi of two affected fetuses and one female fetus was observed. [64Cu]-uptake studies have been performed on 11 diagnostic and 10 control c.v. samples. As the control samples in some cases were found to incorporate more [64Cu] than the corresponding diagnostic sample, this method cannot at present be used for diagnosis. Compiled results on newborn females gave evidence that two carriers expressed the paternal X-chromosome, and two carriers expressed the maternal X-chromosome in in chorionic villi.

Adult↗
PubMed1987

Postmortem Menkes diagnosis from carrier testing of female relatives.

A boy who died at 6 months of age was noted to have sparse, stubby and light hair, pili torti were observed microscopically, and his skin was dry and redundant. As a suspicion of Menkes disease was first raised after his death, serum copper and ceruloplasmin in serum were not measured. Unfortunately, no fibroblasts were available - only fixed and paraffin-embedded samples of brain, spleen and liver. The copper contents of the brain and the liver were lower than in an age-matched control. Fibroblast cultures from the mother, the maternal grandmother, and a maternal aunt of the index patient were analysed for 64Cu-uptake. All these females showed the uptake values expected for Menkes carriers, thus supporting the clinical suspicion of Menkes disease in the index patient. From the above-mentioned results it was highly likely that the index patient had suffered from Menkes disease. Adequate genetic counseling could thus be offered to the family, and in the next pregnancy a first trimester prenatal diagnosis was performed.

Brain Chemistry↗
PubMed1987

Increased vigilance and dopamine synthesis by large doses of tyrosine or phenylalanine restriction in phenylketonuria.

In a group of 9 patients with classical phenylketonuria (PKU) aged 15-24 years we examined the effect of phenylalanine restricted diet on vigilance, as judged by the continuous visual reaction times, and neurotransmitter synthesis, as judged by cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) levels. HVA and 5-HIAA levels decreased significantly with increase in plasma phenylalanine concentration on free diet (p less than 0.01 and p less than 0.0005 respectively). Vigilance improved on phenylalanine restricted diet in 6 of the 7 patients with abnormally long reaction times on free diet. Addition of tyrosine (160 mg/kg/24 h) to the free diet resulted in an increased CSF in the six patients examined. In 14 patients on free diet supplemented with tyrosine, an improvement in vigilance (reaction times at the 90 percentile) was seen in all 12 patients with values longer than the normal mean (264 msec) (p less than 0.001). Tyrosine treatment may be a therapeutical alternative when phenylalanine restriction is impractical.

Adolescent↗
PubMed1987

Regional differences in cardiac myocyte dimensions and number in Sprague-Dawley rats from different suppliers.

Previous experiments conducted in this laboratory have indicated that adult Sprague-Dawley rats obtained from Holtzman Company (H) have hearts that are significantly larger than those obtained from Charles River (CR). To investigate potential differences in cell size and number, isolated myocytes were prepared by retrograde coronary perfusion with collagenase. Cell volume (V) was measured with a Coulter Channelyzer, cell length (L) was measured directly, and cross-sectional area (CSA) was calculated from V/L. Cell number was calculated using data from isolated cells and whole-sectioned tissue. Although V for left and right ventricular myocytes was similar in CR and H rats, myocytes from CR tended to be shorter in L (P less than 0.001), but larger in CSA (N.S.) than myocytes obtained from H rats. In both H and CR, left ventricular V and CSA were greater (P less than 0.01) in endomyocardium than epimyocardium and middle myocardium. Values for V and CSA of right ventricular myocytes were less (P less than 0.01) than those from left ventricles in both H and CR. Hearts from H had 19% more myocytes than those from CR (P less than 0.05). Values for cellular dimensions from CR generally showed less variability than those from H. We conclude that significant regional differences in myocyte size are present in rats from both H and CR. Hearts from H rats have significantly more myocytes than those from weight-matched CR rats. Therefore, investigators should be aware that differences in heart weight and myocyte number can be found in rats of the same strain, but obtained from different suppliers.

Animal Husbandry↗
PubMed1987

Regional changes in myocyte size and number in propranolol-treated hyperthyroid rats.

The effects of beta-adrenergic blockade and hyperthyroidism on cardiac myocyte structure was examined. Isolated myocytes were prepared from controls and rats treated for 10 weeks with desiccated thyroid hormone (T), propranolol, and desiccated thyroid hormone plus propranolol (TP). Cells were collected from the right and left ventricle. Cell volume was measured with a Coulter Channelyzer system. Cell length was measured directly using a phase microscope. Myocyte cross-sectional area was calculated from cell volume/length. In addition, hearts from animals in each group were perfusion-fixed and myocyte volume percent was determined morphometrically from tissue sections. The number of right and left ventricular myocytes was calculated using data from isolated cells and whole-sectioned tissue. Propranolol normalized heart rate in hyperthyroid rats. Heart weight to body weight ratios were elevated to a similar extent in both T and TP groups. Compared with controls, myocyte volume was increased (p less than 0.01) in each region of T and TP. Right ventricles had a greater degree of myocyte hypertrophy than left ventricles in both rat groups treated with thyroid hormones. Cell length was increased (p less than 0.01) in T and TP. Most of the myocyte hypertrophy, however, was due to an increase in cross-sectional area. Although volume was unchanged with propranolol treatment alone, myocytes from each region had an increase in length (p less than 0.01) and a reduction in cross-sectional area (N.S.). Myocyte number was slightly reduced in each treatment group, but changes were not statistically significant. In conclusion, thyroid hormones stimulate myocyte hypertrophy by increasing both length and cross-sectional area. Propranolol modifies myocyte dimensions in both euthyroid and hyperthyroid rats, but does not prevent thyroid hormone induced cardiac hypertrophy.

Animals↗
PubMed1986

Regional differences in myocyte size in normal rat heart.

Three independent methods were evaluated in an effort to obtain reliable values for myocyte size in adult Sprague-Dawley rats. Cell volume was determined from isolated myocytes by a Coulter Channelyzer system. Cell volume was also determined from the product of length and cross-sectional area of isolated myocytes. Additionally, myocyte cross-sectional area was measured morphometrically from electron micrographs of whole perfusion-fixed tissue. A major goal was to determine if anatomical methods used to measure cell volume produce values comparable to the more expeditious and objective Coulter Channelyzer method. The results of these experiments showed that myocyte dimensions obtained from all three techniques were similar. The second major objective was to use the above-mentioned techniques to evaluate regional differences in myocyte size. Myocyte cross-sectional area and volume were significantly larger in the endomyocardium than in the epimyocardium of the left ventricle. Right ventricle myocytes had significantly smaller volumes and cross-sectional areas than did left ventricle myocytes. There were no regional differences in cell lengths. We conclude that the Coulter Channelyzer system gives values for isolated myocyte volume that are similar to values obtained with histometric techniques; values for isolated myocyte cross-sectional area were representative of values obtained from myocytes in whole-sectioned tissue; significant regional differences in myocyte size are present in adult rat hearts; and regional variations in myocyte size are due to differences in myocyte cross-sectional area rather than cell length.

Analysis of Variance↗
PubMed1983

Changes in myocardial cell size and number during the development and reversal of hyperthyroidism in neonatal rats.

Increased workload was produced in newborn rats to study myocyte structure during conversion from hyperplastic to hypertrophic growth. Newborn rats were given L-thyroxine (T4) for 12 days and killed at that time or 20 days after discontinuing T4 treatment. Myocytes were isolated by a perfusion technique with collagenase. Cellular dimensions were determined with a sonic digitizer. Mean cell volumes were also determined with a Coulter counter for comparison with values obtained with the digitizer. Heart weight to body weight ratios were increased 30% in 12-day-old hyperthyroid rats. Cell length increased 22%, and cell volume increased 31% after 12 days of treatment with T4. The calculated number of ventricular myocytes indicated that T4 inhibited rather than stimulated hyperplastic myocyte growth. Twenty days after discontinuing T4 treatment, heart weight to body weight ratio and mean cell volume of treated animals were similar to control values. Cell length, however, remained significantly increased (14%), and cell width was significantly reduced (8%) after reversal of hyperthyroidism. We conclude that excess T4 inhibits hyperplastic myocyte growth in neonatal rats while stimulating hypertrophy of existing myocytes primarily by increasing cell length. Myocytes remained significantly longer after reversal of hyperthyroidism, indicating that structural changes may persist.

Animals↗
PubMed1982

Regional differences in capillary density and myocyte size in the normal human heart.

Significant regional morphometric differences are reported for the normal human left ventricle. Epimyocardial capillary density (2,439 capillaries/mm2) is 21% greater than endomyocardial capillary density (2,014 capillaries/mm2). The minimum intercapillary distance is, therefore, increased in the inner region. Endocardial myocytes (617 micron2) have a 53% greater cross-sectional area than epicardial myocytes (403 micron2).

Adult↗
PubMed1982

Morphometric study of cardiac muscle: the problem of tissue shrinkage.

Comparison of data from morphometric studies dealing with the heart is complicated by the fact that little information dealing with cell size changes during tissue processing is available. To investigate these changes, isolated cardiac myocytes were adhered to glass cover slips of Sykes Moore chambers and photographed after each step of processing for transmission electron microscopy. Six different experiments with a minimum of 10 cells each were followed through the entire procedure after fixation with isoosmolar glutaraldehyde. Cellular dimension changes were determined by tracing individual isolated myocytes after each step of the procedure with a sonic digitizer. Significant cell volume changes occurred after osmium (16 per cent swelling), postosmium wash (10 per cent swelling), and uranyl acetate (25 per cent shrinkage). Hypertonic aldehyde solutions resulted in cellular shrinkage during fixation not found with isotonic solutions. Changes in cell cross-sectional area rather than length were largely responsible for altered cell volumes during any given phase of processing. The results indicate that, although cell volume changes occur during processing, final cell dimensions of embedded cells were not different from unfixed cells. In whole tissue blocks, inclusion of propylene oxide in the procedure resulted in tissue shrinkage which was not observed in isolated myocytes, suggesting that different tissue components react in a variable manner to propylene oxide. After each of the other steps in processing, tissue blocks reacted in a similar manner to the isolated myocytes.

Animals↗
PubMed1980

Morphometric study of endomyocardium and epimyocardium of the left ventricle in adult dogs.

Quantitative light- and electron-microscopic data are reported for the endomyocardium and epimyocardium of the left ventricle in adult dogs. The endomyocardium has a markedly lower capillary density, and larger myocyte cross-sectional area, than the epimyocardium. The sarcolemmal-surface/cell-volume ratio is significantly less in endocardial myocytes. No regional differences were found with regard to capillary diameter, interstitial space volume, or volume percent occupied by blood vessels and myocytes. Likewise, there are no differences in proportions of cardiac cell volume occupied by myofibrils (57%), mitochondria (25%), nuclei (1.5%), T tubes (1.2%), and sarcoplasmic reticulum (2.0%). The ratios of surface areas of T tubes and SR to their respective volumes and to cell volumes do not vary with transmural location. The regional differences and similarities are discussed in relation to general problems of blood flow in the heart and cardiac hypertrophy.

Animals↗
PubMed1979

Differences in regional capillary distribution and myocyte sizes in normal and hypertrophic rat hearts.

Data are reported which show significant regional capillary differences in left ventricular endocardium and epicardium of normal rats and of rats with hyperthyroid-induced cardiac hypertrophy. The epicardial region of control rats has 38% more capillaries than the endocardial region. Control endocardial myocytes are 62% larger in cross-sectional area than epicardial myocytes. Hypertrophic hearts exhibit regional differences in capillary density similar to those in the normal hearts, but there is an overall reduction of 12 and 17.5% in capillary density in both regions. The average cross-sectional area of myocytes increases 34.5% in the epicardium and 22.5% in the endocardium.

Animals↗
PubMedDate not supplied

Change in cardiac myocyte size distribution in aortic-constricted neonatal rats.

Regional changes in cardiac myocyte size and population distribution were examined in Sprague Dawley rats receiving an abdominal aortic constriction at five days of age. At specific time intervals post-constriction, hearts were recovered from constricted animals and weight-matched controls and isolated myocytes were obtained from right and left ventricles using retrograde coronary perfusion with collagenase. Cell volume and cardiac myocyte population distribution curves were determined using a Coulter Channelyzer system. Cell length was measured directly using a Bioquant Image Analysis system. Myocyte cross-sectional area was calculated from cell volume/length. By three months of age, heart weight and heart weight-body weight ratio in constricted animals had increased by approximately 115% (p less than 0.001) in females and 85% (p less than 0.001) in males compared to controls. Between 15 and 90 days of age, the growth response, as indicated by increased cell volume, was approximately 4x greater in constricted females and 2.5x greater in constricted males compared to corresponding controls. This increase was manifested by a shift in the mean size of the myocyte population to the right and a substantial widening of the distribution. Most of the enlargement was due to increased cross-sectional area, with only a moderate contribution from increased cell length. Significant increases in size were seen in both left and right ventricles. By three months of age, a significant interaction was apparent between aortic constriction and sex. The capacity for hypertrophy was greater in the smaller myocytes in female rats of similar age compared to males. The final degree of hypertrophy was similar for male and female rats, possibly indicating a critical upper limit in cell size for cardiac myocytes.

Animals↗
PubMedDate not supplied

Failure of propranolol to prevent chronic hyperthyroid induced cardiac hypertrophy and multifocal cellular necrosis in the rat.

The effect of excess thyroid and thyroid plus propranolol on right and left ventricular structure was examined. Perfusion fixed hearts from untreated adults and those treated for 10 weeks with thyroid, propranolol, and thyroid plus propranolol were embedded in plastic and sectioned for light and electron microscopy. Hyperthyroidism stimulated a significant increase in heart rate, oxygen consumption, and systolic blood pressure. Propranolol was effective in normalizing the heart rate of hyperthyroid rats, but did not affect oxygen consumption or blood pressure. Both left and right ventricular weight increased similarly in thyroid and thyroid-propranolol treated animals, but right ventricular mass increased more than left ventricular mass in both groups. The majority (21 of 24) of right ventricles from thyroid and thyroid-propranolol treated animals had multifocal areas of histologically detected fibrosis. Left ventricular fibrosis was absent or minimal in both hyperthyroid groups. Neither left nor right ventricular fibrosis was observed in control or propranolol only treated animals. We conclude that beta adrenergic stimulation is unnecessary for thyroid induced cardiomegaly, and excess thyroid hormones induce right ventricular fibrosis which is not prevented by propranolol.

Animals↗