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Biomedical subjects

A M Gerdes

Publications and source records attributed to A M Gerdes.

At least 73 records · Page 4Linked to original sources
PubMed1991

Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas. 1. Developing and established hypertrophy.

The effects of a large arteriovenous fistula on left and right ventricular hemodynamics and cardiac myocyte size were examined in adult rats at 1 week and 1 month after surgery. Cardiac output, left ventricular function, and right ventricular function were evaluated before obtaining isolated myocytes for cell size measurements. Average heart weight increased 35% at 1 week and 86% at 1 month in rats with fistulas. In general, myocyte hypertrophy was due to a proportional increase in length and width (length/width ratio remained constant). This change was more evident in the large hearts from rats with 1-month fistulas. At both the 1-week and 1-month intervals, the hypertrophic response of right ventricular myocytes was slightly greater than that observed in the left ventricle or interventricular septum. Left ventricular systolic pressure and dP/dtmax were significantly reduced at 1 week but returned to normal after 1 month of overloading. Left ventricular end-diastolic pressure was increased approximately fivefold and twofold at 1 week and 1 month, respectively. Right ventricular systolic pressure and dP/dtmax were increased at both intervals examined. We conclude that severe volume overloading from a large aortocaval fistula in the rat is characterized by 1) depressed left ventricular function at 1 week followed by a large compensatory hypertrophy and near normal function at 1 month, 2) right ventricular pressure overload, and 3) changes in myocyte shape that resemble normal physiological growth.

Animals↗
PubMed1991

Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas. 2. Long-term effects.

Regional changes in hemodynamics and cardiac myocyte size were examined in adult rats 5 months after creating a large aortocaval fistula. At that time, cardiac output, left and right ventricular pressures, and left and right ventricular dP/dtmax were measured. Subsequently, isolated cardiac myocytes were collected from the left ventricle, right ventricle, and septum for cell size measurements. Compared with sham-operated controls, percent dry weight was reduced in the liver and kidney but was unchanged in the lung. Heart rate, left ventricular systolic pressure, left ventricular dP/dtmax, and systolic aortic pressure were not changed in rats with fistulas. However, cardiac output, stroke volume, left ventricular end-diastolic pressure, and all measured parameters in the right ventricle were significantly increased. Mean cell volume and the ratio of heart weight to body weight were both elevated 92%. Cell volume, cell length, and cross-sectional area increased significantly in each heart region examined. Hypertrophy was more pronounced in cells from the right ventricle and the endomyocardium of the left ventricle. The percentage of cells with mononucleation or binucleation was not changed in any heart region of rats with fistulas. In summary, despite evidence of renal and hepatic congestion, most indexes of cardiac function were normal or elevated 5 months after creation of a large volume-overload-induced hypertrophy. Data from isolated cardiac myocytes suggested that cellular hypertrophy, rather than hyperplasia, was responsible for the increased cardiac mass.

Animals↗
PubMed1991

Effect of angiotensin converting enzyme inhibition on pressure-induced left ventricular hypertrophy in rats.

The influence of angiotensin converting enzyme inhibition on the development of left ventricular (LV) hypertrophy due to stenosis of the aortic arch was studied in female Sprague-Dawley rats. The aortic arch was banded to an outer diameter of 1.0 mm. After 14 days, LV and right ventricular functional parameters and transstenotic pressure gradient were measured in anesthetized rats. In addition, regional heart weights were determined, and myocytes of three different heart regions were isolated and subjected to morphometric analysis. To inhibit the angiotensin converting enzyme, ramipril was administered orally by gavage in a single daily dose of 1 mg/kg. Rats with aortic stenosis showed a marked increase in LV systolic pressure, mean prestenotic aortic pressure, and LV stroke work compared with sham-operated rats and demonstrated a systolic transstenotic pressure gradient of 82 mm Hg. This increase in LV hemodynamic load was paralleled by the development of LV hypertrophy as determined by a 37% increase in LV weight and by a 20% increase in cell volume of isolated LV myocytes. Concomitant ramipril treatment did not significantly affect LV functional parameters. The transstenotic pressure gradient was the same as in untreated rats with aortic stenosis. Likewise, the weight gain of the LV as well as the development of cellular hypertrophy of the LV were not influenced. Thus, in this model, angiotensin converting enzyme inhibition did not reduce the development of LV hypertrophy independent of the hemodynamic load.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Influence of age, growth, and sex on cardiac myocyte size and number in rats.

The effects of altered neonatal nutrition on cardiac myocyte size and number was examined in 21-day-old and 3-month-old rats. Nutritional differences in growth rate were produced in newborns by adjusting litter size to four (fast-growing), eight (normally growing), or 16 (slow-growing) pups per litter. Isolated myocytes were prepared from animals in each group to evaluate changes in cell size and number. Heart weight (mg +/- S.D.), at 21 days of age, was 398 +/- 51 for "fast-growing" rats, 329 +/- 43 for "normally growing" rats, and 228 +/- 24 for "slow-growing" rats. Body weights showed a comparable decline with reduced nutrition. In adults, treatment-related differences in body and heart weight were present in males but not females. "Slow-growing" rats had 21% fewer myocytes than "fast-growing" rats at 21 days of age, a change that persisted in adults. Values for myocyte number from "normally growing" rats were intermediate between those of "fast and slow-growing" rats at both 21 days and 3 months of age. In each heart region of weanling rats, myocyte length and volume were smallest in 16 per litter rats. Cellular dimensions increased progressively with better nutrition.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

Changes in heart function and cardiac cell size in rats with chronic myocardial infarction.

Myocardial infarctions were induced in rats by ligation of the left anterior descending (LAD) coronary artery. After 4 weeks, parameters of left (LV) and right ventricular (RV) function and of peripheral circulation were measured in the intact, anesthetized animals. The morphology of the heart chambers was examined at the macroscopic and cell size level. In animals with slight reduction in LV function, LVEDP was elevated from 3.4 +/- 0.8 to 8.8 +/- 1.5 mmHg, LV stroke work was reduced by 14%, and dP/dtmax of both ventricles was depressed by 10% compared with sham-operated controls. Myocytes isolated from the LV and RV were elongated to some extent and had a greater cell volume, but there was no change in heart weight. These rats had infarctions that were small or medium in size. In rats with severe depression in left heart function, cardiac output, LVSP, LV stroke work, mean arterial pressure, and the LV weight/body weight ratio were markedly lower than in sham-operated controls. LVEDP was elevated up to 32 +/- 2 mmHg. These rats had large infarctions. RVSP, RV weight/body weight ratio, and the volume of myocytes isolated from the RV were doubled. RV stroke work was increased by 58%. Myocytes from the LV, RV and from the septum were elongated to about the same extent. The septum had developed a 23% hypertrophy. Histological examination of the lungs revealed marked thickening of the tunica medica of small pulmonary arteries with narrowing of the lumen. These changes are considered to represent the morphological basis for the increased pulmonary vascular resistance that was associated with RV pressure overload and hypertrophy.

Animals↗
PubMed1990

Influence of hypothyroidism and the reversal of hypothyroidism on hemodynamics and cell size in the adult rat heart.

Hypothyroid-induced atrophy of cardiac myocytes was examined in adult female rats in an effort to correlate hemodynamic and cellular changes associated with this disorder. Additional rats were studied 6 weeks after discontinuing antithyroid treatment to determine if structural and functional changes were completely reversible. To induce hypothyroidism, rats were injected daily with propylthiouracil (PTU) for 4 weeks. Control animals were injected similarly with Tris buffer. At the end of the treatment period, hemodynamic measurements were made prior to obtaining isolated myocytes. Cell volume, length, and cross-sectional area were obtained from the septum, and left and right ventricles of treated and untreated rats. After four weeks treatment with PTU, body weight was unchanged but heart weight was significantly reduced by 24%. Characteristic hemodynamic changes associated with hypothyroidism in the rat were noted (eg. reduced heart rate, cardiac output, dP/dtmax, and ventricular pressure). Cell volume was significantly smaller in hypothyroid rats primarily due to a reduction in myocyte cross-sectional area. The hemodynamic and cellular response to hypothyroidism was similar in the right and left ventricle. Six weeks after discontinuing PTU treatment, cellular and hemodynamics changes had returned to normal. It was concluded that hypothyroidism caused a true cardiac atrophy which was reversible. Reduced myocyte cross-sectional area was responsible for most of the myocyte atrophy.

Animals↗
PubMed1990

Influence of ramipril on right ventricular hypertrophy induced by pulmonary artery stenosis in rats.

The influence of the angiotensin-converting enzyme (ACE) inhibitor ramipril (1 mg/kg orally in a single daily dose) on right ventricular (RV) hypertrophy was studied in Sprague Dawley rats. The pulmonary artery was banded to an outer diameter of 1.7 mm. After 14 days, left (LV) and RV hemodynamic parameters were measured in anesthetized animals. Furthermore, regional heart weights were determined, and myocytes of three different heart regions were isolated and subjected to morphometric analysis. Pulmonary artery stenosis caused a marked increase in RV systolic blood pressure (SBP) without alteration of LV functional parameters as compared with sham-operated animals. Correspondingly, the weight of the RV free wall as well as the RV cell volume were increased to about the same extent, while the LV weight was unchanged. Administration of ramipril to pulmonary artery-constricted animals slightly reduced LV SBP and LVdP/dtmax as compared with banded animals without treatment. The increase in RV SBP and the weight gain of the RV free wall were not affected, however. In contrast, the increase in cell volume of isolated myocytes was less pronounced in this group (+27% as compared with +58% in untreated animals). Because there were no differences in water content of the tissue, interstitial or cellular edema cannot be responsible for this discrepancy. Thus, ACE inhibition with ramipril appears to blunt the cellular hypertrophy in this model without affecting the weight gain of the RV.

Analysis of Variance↗
PubMed1990

Clinical expression of Menkes syndrome in females.

Three female patients with Menkes syndrome are described. Clinically, they have typical Menkes syndrome. Biochemically, they have significantly increased 64Cu-uptake in cultured fibroblasts. The chromosomal analysis was normal for two of the patients and abnormal for one patient (45X/46XX mosaicism).

Child, Preschool↗
PubMed1990

Plasma amino acids in term neonates and infants with phenylketonuria before and after institution of the diet.

The plasma amino acid concentrations were measured in 12 neonates with phenylketonuria (PKU). Blood samples were taken when fasting and two hours after a meal. The individual amino acid concentrations, the glycine/valine ratios, and the total amino acid concentrations were mutually compared and also compared to reference intervals. When the diet was instituted and plasma phenylalanine decreased, we observed a normalization of the postprandial response of isoleucine, leucine, tyrosine, and valine.

Amino Acids↗
PubMed1990

Plasma amino acids in phenylketonuric children treated either with phenylalanine-free amino acids or a protein hydrolysate.

The plasma amino acid concentrations were measured in 10 children with phenylketonuria (PKU) on the phenylalanine-free amino acid mixture Phenyldon and 9 PKU children on the phenylalanine-free protein hydrolysate Albumaid. The blood samples were taken fasting and two hours after the meal. The individual amino acid concentrations, the glycine/valine ratios, and the total amino acid concentrations were mutually compared and also compared to reference intervals. No differences of the concentration of phenylalanine on the two diet formulas were observed. Children on Phenyldon showed fasting and postprandial isoleucine higher than the reference intervals. Furthermore, a postprandial increase of several amino acids was observed on both diet formulas. This response was statistically significant in children on Phenyldon.

Amino Acids↗
PubMed1989

[Has Menckes' disease disappeared? Clinical picture and postnatal diagnosis].

Menkes disease is an X-linked recessive disease with an unknown disturbance in the copper-metabolism. We have been diagnosing patients for the last 15 years. Until 1978, six Danish families with Menkes disease were detected. Since 1978 we have only diagnosed one additional patient and one affected fetus in one of the already known families. As the incidence should be about 1 in 45,000 liveborn males, three additional patients should have been seen since 1978. To increase the chances of diagnosing all Danish Menkes patients the clinical symptoms are described. Until now, we have diagnosed 115 Menkes patients and have been in contact with more than 209 Menkes families from many different countries. If we compare the number of inhabitants per Menkes family in different countries, we obtain the following figures, 0.86 x 10(6) inhabitants per Menkes family in Denmark, increasing to 5.21 x 10(6) inhabitants per Menkes family in Italy. Finally some recent experience with copper therapy for treatment of Menkes patients is described.

Brain Diseases, Metabolic↗
PubMed1989

[Isovaleric acidemia].

The three first cases of isovaleric acidemia diagnosed in Scandinavia are described. The disorder is characterized by periodic vomiting, lethargy and coma accompanied by ketoacidosis and a "sweaty feet" odour. These attacks are often triggered of by upper respiratory tract infections or by ingestion of large amounts of protein. Often there are feeding difficulties because these children have aversion to protein-containing foods. Isovaleric acidemia can be subdivided into two types: an acute neonatal form and a chronic intermittent form. The basic defect is deficient activity of isovaleryl-CoA dehydrogenase, resulting in increased urinary excretion of mainly isovaleryl-glycine and 3-hydroxy-isovaleric acid. The defective gene is assigned to the long arm of chromosome 15, and at least five different mutations among 15 patients have been demonstrated. Therapy is symptomatic with correction of the metabolic acidosis and protein restriction and long term treatment with oral glycine and possibly carnitine.

Acidosis↗
PubMed1989

First-trimester diagnosis of Menkes disease: intermediate copper values in chorionic villi from three affected male fetuses.

Chorionic villus samples with copper contents of 1.91, 4.2, 5.6, and 6.3 ng/mg were observed in four cases with male karyotypes. These values were outside the range for unaffected males (0.30-0.85 ng/mg), and three of them were outside the control range (0.20-2.39 ng/mg). But these three values were below the values previously observed for affected Menkes fetuses (12.0-24.8 ng/mg). Follow-up by 64Cu uptake studies on the amniotic fluid cells was performed in three of these cases. A combination of 64Cu uptake and chase experiments on the amniotic fluid cells showed more convincingly than 64Cu uptake per se the direct copper values of 4.2 and 5.6 ng/mg to correspond to affected fetuses. Amniotic fluid cells from the male fetus with the CV copper value of 1.9 ng/mg showed normal results. The CV copper value of 6.3 ng/mg was considered pathognomonic for Menkes disease. The pregnancy was terminated, and the diagnosis was confirmed on fetal fibroblasts. Maternal deciduum prepared from the placentae showed in one of the cases with an affected fetus copper values ranging from 1.5 to 5.7 ng/mg. In six additional diagnostic cases, the copper content was determined in both CV samples and maternal deciduum. In three of these cases with normal CV sample copper, maternal decidua values of 4.85-7.8 ng/mg copper were observed. These results show that maternal deciduum contamination of a CV sample could cause a false-positive diagnosis.

Amniotic Fluid↗
PubMed1989

Tetrahydrobiopterin and Parkinson's disease.

Two patients with Parkinson's disease were treated with 1 g tetrahydrobiopterin (BH4) for 5 days. Clinical improvement was not observed. In the cerebrospinal fluid (CSF) a 4-8 fold increase in the concentration of homovanillic acid (HVA), and a 3-fold increase in the concentration of 5-hydroxyindole acetic acid (5-HIAA) was measured. However, the concentration of HVA reached, was only approximately half as high, as that of patients treated with madopar (DOPA + benserazid). In urine, the excretion of HVA increased 13-37 fold, when the patients were treated with madopar, whereas no increase in the HVA excretion was measured after the BH4 administration. Additionally, 2 patients with Parkinson's disease were treated with 1 g BH4 in combination with 15 g tyrosine for 3 days, and 1 parkinsonian patient was treated with 15 g tyrosine daily for 7 weeks. No increase in the CSF concentrations of HVA or 5-HIAA was observed. The results suggest, the BH4 in the dosage used, is not effective in the treatment of Parkinson's disease.

Adult↗
PubMed1989

Right ventricular performance after monocrotaline-induced pulmonary hypertension.

Chronic pulmonary hypertension leads to a compensatory hypertrophy of the right ventricle (RV). Performance of the hypertrophied heart has been shown to vary depending on the type and severity of the overload, the species, age, and sex of the animal in which the hypertrophy is induced and the ventricle to which the overload is applied (left ventricle vs. right ventricle). In this study we employed two novel approaches to examine the performance of the hypertrophied right ventricle in male Sprague-Dawley rats. First, monocrotaline (MCT), a pyrrolizidine alkaloid isolated from the plant Crotalaria spectabilis, was used to noninvasively induce chronic pulmonary hypertension, RV pressure overload, and RV hypertrophy. After 5 wk the RV-to-(left ventricle + septum) ratio was increased by 94% over control. The volume of isolated right ventricular myocytes from MCT-treated rats was increased due primarily to an increase in cell cross-sectional area. Second, a stable, isolated, working heart preparation, normally used to study left ventricular function, was modified to study right ventricular function. In vitro ventricular performance of severely hypertrophied hearts was elevated compared with control hearts at all preloads. Significant elevations in positive and negative maximum pressure development (dP/dtmax) suggested that both the rate of pressure development and the rate of relaxation were enhanced. Coronary flow and RV-diastolic pressure were similar in the MCT and control group. Thus RV hypertrophy caused by a chronic pressure overload induced by MCT resulted in enhanced ventricular performance with no evidence of failure.

Animals↗
PubMed1988

Increased neurotransmitter biosynthesis in phenylketonuria induced by phenylalanine restriction or by supplementation of unrestricted diet with large amounts of tyrosine.

Seven phenylketonuria (PKU) patients aged 15-24 years were allowed unrestricted diet for 3 weeks. Three of these patients performed well on unrestricted diet according to visual reaction time variability (RTv 50-100 ms) and did not show significant changes when returning to the phenylalanine-restricted diet (RTv 70-100 ms). Neither did the concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) change significantly. Four of the patients, however, performed rather poorly (RTv 120-220 ms) on unrestricted diet and improved significantly (P less than 0.03) when the diet was restored (RTv 70-150 ms). The improvements were accompanied by significant (P less than 0.01 and P less than 0.02) increases (mean 52% and 109%) in CSF levels of HVA and 5-HIAA. Five PKU patients aged 15-23 years were allowed unrestricted diet or unrestricted diet supplemented with various amounts of tyrosine (106-194 mg/kg per 24 h). Two of these patients performed very well on unrestricted diet (RTv 60 ms) and showed little change when the unrestricted diet was supplemented with tyrosine (RTv 70 ms and 80 ms). The three other patients, who performed rather poorly (RTv 120-220 ms), improved significantly (P less than 0.03) when the unrestricted diet was supplemented with tyrosine (RTv 70-140 ms). HVA in CSF increased significantly (P less than 0.01) with the tyrosine supplement when the amount exceeded a threshold of approximately 80 mg/kg per 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Variability in clinical expression of Menkes syndrome.

Six patients with Menkes syndrome are described, who differ from patients with the classical form of Menkes syndrome because of their longer survival; some of them also exhibited a milder manifestation of symptoms. Based on the present data and a summary of seven case reports describing Menkes patients with long survival, it may be possible to divide these patients into two subgroups: one group of severely affected patients with long survival and another group of very mildly affected patients with late onset of symptoms. Perhaps only the latter represents a true subgroup of Menkes syndrome. The possible benefits of copper therapy are discussed.

Brain Diseases, Metabolic↗