The physical dimensions of the human neonatal cardiovascular system.

To establish a data base for studies which seek to model and simulate the human perinatal cardiovascular system, we dissected three stillborn, full-term infants and measured the length, internal diameter, and wall thickness of over 1000 blood vessel segments. Cumulatively, these segments represent the major and minor vessels of the systemic and pulmonary circulation at birth. Statistical analysis showed that the methods used to obtain these physical dimensions were highly consistent and that storage of tissue samples in 10 percent formaldehyde solution caused a linear shrinkage of approximately 6.3 percent. A topological code was developed to illustrate the network relationships of blood vessel segments. An example of data utilization based on the topological code is presented and discussed.

Corticosteroids and lung surfactant levels in adult male rats.

Following lung instillation in adult male rats of 3.4 mumol hexavalent chromium (K2Cr2O7) dissolved in 0.5 ml of 0.9% NaCl, increased levels of lung surfactant could be detected after 48 h. The blood serum concentration of corticosterone was elevated in these animals. Blood serum thyroxine and triiodothyronine showed an initial increase after lung instillation of hexavalent chromium followed by a decline. Metabolism of testosterone by the alveolar macrophages to 17 beta-hydroxy-5 alpha-androstane-3-one and 5 alpha-androstane-3 alpha, 17 beta-diol was reduced 6 and 12 h after the K2Cr2O7 instillation, which was also associated with damage of lung cell function and decreased uptake by the alveolar macrophages of Candida albicans particles. As early as 12 h after s.c. administration of 400 micrograms dexamethasone/100 g body wt, increased levels of lung surfactant could be measured. At this time the lungs showed no signs of cellular damage, and metabolism of testosterone as well as uptake of Candida albicans particles by the alveolar macrophages were normal. Lower s.c. doses of dexamethasone did not result in raising the levels of lung surfactant in 12 h. Within 12 h after s.c. administration of large doses of testosterone, dihydrotestosterone or dehydroepiandrosterone no measurable effects on the levels of lung surfactant could be measured. Since animals treated with dexamethasone (200 micrograms/100 g body wt) or long-acting synthetic ACTH (100 micrograms i.m. Synacthen Depot/100 g body wt) for 5 days after lung instillation of K2Cr2O7 had extremely high levels of lung surfactant, it is concluded that the corticosteroids in adult rats may help to create augmented surfactant levels following lung intoxication. This could proceed via stimulation of surfactant production and reduction of surfactant removal. Different aspects of lung surfactant metabolism are discussed.

Metabolism of testosterone to 17 beta-hydroxy-5 alpha-androstane-3-one and 5 alpha-androstane-3 alpha, 17 beta-diol in alveolar macrophages from rat lung--II. Effects of intratracheal instillation of 3.4 mumol K2Cr2O7.

Activity of the steroid 5 alpha-reductase in pulmonary alveolar macrophages from adult male rats has been investigated in vitro. Intratracheal instillation of 3.4 mumol K2Cr2O7 lowered the enzyme activity within 6 h, and the reduction was significant on the subsequent 2, 4 and 7 days. The activity of this enzyme was significantly decreased only 6 and 24 h after instillation when measured in the 800 g supernatant fraction of whole lung. Instillation of 3.4 mumol K2Cr2O7 increased serum levels of corticosterone. Serum levels of triiodothyronine and thyroxine decreased except for a transient increase 3 h after the K2Cr2O7 instillation. Subcutaneous administration of 200 micrograms dexamethasone/100 g b.wt, 200 micrograms/100 g b.wt of testosterone, 17 beta-hydroxy-5 alpha-androstane-3-one (5 alpha-DHT), dehydroepiandrosterone or corticosterone had no effect on the 5 alpha-reductase activity of the pulmonary alveolar macrophages within 12 h. The combined treatment with dexamethasone s.c. and intratracheal instillation of 3.4 mumol K2Cr2O7 reduced the steroid 5 alpha-reductase activity in the pulmonary alveolar macrophages to about 25% of controls. Measurement of the steroid 5 alpha-reductase activity in pulmonary alveolar macrophages as an index of lung damage when exposed to toxic material is discussed.

Metabolism of testosterone to 17 beta-hydroxy-5 alpha-androstane-3-one and 5 alpha-androstane-3 alpha, 17 beta-diol in alveolar macrophages from rat lung.

5 alpha-Reduction of testosterone was observed in lung cells obtained by bronchoalveolar lavage (greater than 95% macrophages) from the rats. This activity was inhibited by progesterone and corticosterone. Production of 17 beta-hydroxy-5 alpha-androstane-3-one and 5 alpha-androstane-3 alpha, 17 beta-diol from testosterone was higher in rat pulmonary alveolar macrophages than by the 800 g supernatant fraction of whole lung homogenate from the same animals. Alveolar macrophages from rats treated with the 5 alpha-reductase inhibitor 17 beta-N,N-diethylcarbamoyl-4-aza-4-methyl-5 alpha-androstane-3-one (5 mg/100 g b.w., s.c.) showed decreased metabolism of testosterone to 17 beta-hydroxy-5 alpha-androstane-3-one and 5 alpha-androstane-3 alpha, 17 beta-diol 4 h after treatment. This metabolism was also decreased in alveolar macrophages from rats exposed to potassium dichromate by intratracheal instillation. When bovine alveolar macrophages were incubated with potassium dichromate, 5 alpha-reduction of testosterone decreased significantly. The function of steroid 5 alpha-reduction in alveolar macrophages is currently not known.

Ileal metabolism in vitro of testosterone to 4-androstene-3 alpha, 17 beta-diol.

Testosterone metabolism to 4-androstene-3 alpha, 17 beta-diol by the 800 g supernatant fraction of ileum from male and female rats was investigated. Ileal production of this testosterone metabolite was higher in mature female animals than in mature males. This difference could be eliminated by administration of large doses estradiol-17 beta to mature male rats. Immature animals showed low ileal production of 4-androstene-3 alpha, 17 beta-diol before being weaned from their mother.

Metabolism in vitro of testosterone (T) to 17 beta-hydroxy-5 alpha-androstane-3-one (DHT) and 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha) by the 800 g supernatant fraction of ileum from rats.

The 800 g supernatant fraction of ileum from rats was incubated with testosterone and production of 17 beta-hydroxy-5 alpha-androstane-3-one and 5 alpha-androstane-3 alpha,17 beta-diol measured. No difference in this production could be determined between ileum from mature female and mature male animals. Ileum from immature rats staying with their mothers from day 12 to day 21 showed increased 5 alpha-reduction of testosterone on days 15, 17 and 21. Ileal metabolism to 17 beta-hydroxy-5 alpha-androstane-3-one and 5 alpha-androstane-3 alpha,17 beta-diol was increased in immature animals on day 25 of extrauterine life when consuming rat chow and water ad libitum from day 21. This increase could not be demonstrated on day 28. Immature and mature animals treated either with long-acting ACTH or dexamethasone showed increased ileal conversion of testosterone to the two 5 alpha-reduced metabolites determined. Ileum from mature male rats injected, subcutaneously, with arabinosylcytosine every 8th h for 2 days exhibited increased metabolism of testosterone to 17 beta-hydroxy-5 alpha-androstane-3-one and 5 alpha-androstane-3 alpha,17 beta-diol from the 1st to the 6th day after the last injection of arabinosylcytosine. Different aspects of intestinal metabolism of testosterone are discussed.