Substrate metabolism in the perfused lung: Response to changes in circulating glucose and palmitate levels

Shaw, Mary E.; Rhoades, Rodney A.

doi:10.1007/bf02533313

Cited by 30 publications

(12 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In samples containing the larger amounts of substrate, incorporation into phosphatidylcholine increased approximately five-fold. This is likely due to greater substrate availability and is in agreement with the findings of Shaw and Rhoades (28). Furthermore, no differences were found between the two study groups indicating that large variations in endogenous fatty acids pools either do not occur, or do not necessarily affect uptake into phosphatidylcholine.…”

Section: Resultssupporting

confidence: 90%

Enhancement of Fetal Lung Surfactant Production by Aminophylline

et al. 1979

View full text Add to dashboard Cite

Summarystudies analyzing the biochemical effects of aminophylline on the Antepartum administration of aminophylline to pregnant rabbits production of pilmonary surfactant phospholipid^. These studies are a part of a continuing effort to evaluate the metabolic effects, resulted in P~~~P~~'~P~~~ to be and potential toxicity of aminophylline as a preventive important components of pulmonary surfactant. Increases in the tissue content and synthesis of saturated ~hos~hatidvlcholine and agent for idiopathic respiratory distress syndrome.-* phosphatidylinositolwere found in lung slice prepara60ns obtained from fetuses previously treated with aminophylline. Synthesis of MATERIALS AND METHODS phospholipids was measured using labeled palmitate, oleate, andThe fetal rabbit lung slice model was used. Details of gestational glucose as precursors. The results showed increased de novo timing as well as treatment schedule are described elsewhere (3). production of these lipids, and that glucose and glycogen may On the 27th day of gestation, the fetuses were delivered by serve as important precursors. There was a significant reduction cesarean section with the doe under general anesthesia. The fetal in triglyceride content while free fatty acids increased suggesting lungs were excised and placed in cold Krebs-Ringer buffer as increased lipolysis in the aminophylline-treated groups, but this described by O'Neil and Tierney (23). The lungs were rinsed in did not measurably affect the rate of labeled palmitate incorpora-the same buffer, blotted dry, and slices of 1000 micron thickness tion into total phospholipids.prepared. Approximately 300 mg tissue were transferred into metabolic flasks containing 4.5 ml Krebs-Ringer bicarbonate buffer and 5% bovine serum albumin (Pentex fraction V). IncorSpeculation poration of radiolabeled substrates into various tissue lipids was Prenatal treatment with aminophylline may prove to be an measured utilizin the following compounds in the concentrations k effective means of preventing idiopathic respiratory distress syn-specified: 32 PM' C-~-palmitic acid (0.65 ~C i /~m o l e ) , 32 PWH-9, drome. This method could be an effective and safe means of 10 oleic acid (7.8 PCi/Pmole), and 35 mM'4C-U glucose (18.5 accelerating pulmonary surfactant production before premature ~C i /~m o l e ) .Radiochemicals were purchased from New England delivery.Nuclear Corporation. Fatty acid substrates were bound to albumin. as their sodium salts by titration with 0.1N NaOH and heating to 80°C. After cooling, the lipids were added to a 5% solution of Maturation of fetal mammalian lungs can be accelerated by albumin in Krebs-Ringer bicarbonate buffer. The flasks were antenatal administration of glucocorticoids. Decreased morbidity weighed before and after addition of tissue and tissue weight was of prematurely born infants has been reported in human infants determined by the weight difference of flasks. After equilibration (22) and experimental evidence of increased pulmonary surfactant for 45 sec with 95% Oz and 5% CO...

show abstract

Section: Resultssupporting

confidence: 90%

Enhancement of Fetal Lung Surfactant Production by Aminophylline

et al. 1979

View full text Add to dashboard Cite

show abstract

“…The medium then was aspirated, work was confirmed by Salisbury-Murphy et al (18) in rabbit and and the tissue was washed with ice-cold 0.Wo saline until the wash later by Wang and Meng (24) in the rat. Shaw and Rhoades (19) was free of radioactivity (about five washes). The slices were then in the perfused rat lung reported that high concentrations of removed with forceps to a Dounce homogenizer and homogenized palmitate (1.8 mM) inhibited glucose oxidation to COz, suggesting in 1.6 ml of cold 0.9% saline.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Adaptation in Developing Lung

1980

View full text Add to dashboard Cite

incorporation into lipids was concentrations were chosen because they gave optimal rates of greatest at 18 to 19 days of fetal development, at which time the oxidation. lung content of nonesterified fatty acids was highest.The flasks were fitted with rubber caps and polypropylene center wells and incubated in a shaking water bath at 37OC for Speculation one hr. Under these conditions, production of I4COz from labeled substrates was linear for at least 2 hr. At the end of the incubation, Tbe changes substrate oxidation and Utili~atioll observed in 0.3 ml of hymine hydroxide was injected through the serum cap developing lung probably reflect ch~nges in the avdabmty of into the center well to trap evolved "COz, the reaction was substrates and requirements for precursors to support functional terminated, and COz was released by the injection of 1 ml of 2m and mor~hologic differentiation of lung-Changes in cpochrome trichloroacetic acid through the cap down the side of the flask into oxidase activity in the postnatal period may reflect differential the incubation medium. After 45 min of further incubation, the lung growth.contents of the center well were transferred to counting vials containing 10 ml of Emnofluor (33), and radioactivity was measured in a liquid scintillation counter (35). Blanks were incubated The developing lung requires energy for growth and maturation along with the samples and treated in the same way. Standards as well as for the synthesis of surface active phospholipids which were prepared containing 100 pl of the incubation mix and counted maintain postnatal alveolar stability. Although there is consider-in 10 ml of Aquasol (33). The flasks or medium were not oxygenable information concerning glucose and fatty acid metabolism in ated because this did not affect the rate of substrate oxidation to adult lung, little is known about fatty acid and glucose oxidation COz. in the developing lung. Early work by Geyer et al. (8) showed that For measurement of fatty acid incorporation into lipid, slices adult rat lung slices oxidized radiolabeled triolein and octanoic (50 to 200 mg wet wt) were incubated at the same substrate acid to 14c02. Subsequent studies by Felts (7) using adult rat lung concentrations in 2 ml of medium. The reaction was terminated slices demonstrated oxidation of [1-"clpalmitate to I4Coz. This by transfer of the flask to ice. The medium then was aspirated, work was confirmed by Salisbury-Murphy et al. (18) in rabbit and and the tissue was washed with ice-cold 0.Wo saline until the wash later by Wang and Meng (24) in the rat. Shaw and Rhoades (19) was free of radioactivity (about five washes). The slices were then in the perfused rat lung reported that high concentrations of removed with forceps to a Dounce homogenizer and homogenized palmitate (1.8 mM) inhibited glucose oxidation to COz, suggesting in 1.6 ml of cold 0.9% saline. The homogenate was transferred to that under some conditions palmitate may be a preferred substrate. a stoppered centrifuge tube, 6 ml of chloroform:methan...

show abstract

“…The functional importance of such a high glycolytic flux of glucose to lactate in an organ that has one of the highest Po2 in the body is not fully understood. Glucose utilization and lactate production are affected by circulating glucose levels (16,19) and may account for some of the discrepancies in the literature regarding glucose uptake and lactate production. Also, it is important to point out that earlier studies, in which red cells were used as part of the perfusion medium, show abnormally high values for glucose uptake and lactate production (5).…”

Section: Mediummentioning

confidence: 99%

“…This section presents the methodology of an IPL preparation we have found to be appropriate for a variety of studies (10,14,18,19). In this method lungs are positive ventilated and perfused with an artificial medium which is recirculated at a constant flow.…”

Section: Isolated Perfused Lung Techniquementioning

confidence: 99%

See 1 more Smart Citation

Isolated perfused lung preparation for studying altered gaseous environments.

Rhoades¹

1984

Environ Health Perspect

View full text Add to dashboard Cite

The isolated perfused lung (IPL) preparation is ideally suited to investigate lung dynamics and cellular function, and is easily adapted to investigating biochemical and physiological responses to environmental insults. The IPL offers several advantages which permit one to study endothelial/epithelial interactions that are often disrupted with other model systems (e.g., isolated cells, minces, slices, homogenates, etc.). The IPL developed in our laboratory was devised for the rat lung and allows four lungs to be perfused simultaneously in which control over ventilation, flow, pressure, pH, P02 and Pco2 can be maintained.Isolated lungs perfused for 1 to 2 hr at a flow rate of 10 mL/min exhibit less that 2% weight gain, maintain normal ATP levels, and exhibit linear substrate uptake. Mechanisms leading to changes in vascular and airway resistance, lipid metabolism, vasoactive hormones, blood gases and changes in vascular permeability mediated by environmental insults can be quantified in the IPL preparation.

show abstract

Substrate metabolism in the perfused lung: Response to changes in circulating glucose and palmitate levels

Cited by 30 publications

References 25 publications

Enhancement of Fetal Lung Surfactant Production by Aminophylline

Enhancement of Fetal Lung Surfactant Production by Aminophylline

Metabolic Adaptation in Developing Lung

Isolated perfused lung preparation for studying altered gaseous environments.

Contact Info

Product

Resources

About