Cyclosporin in pulmonary sarcoidosis.
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Cyclosporins↗
Biomedical subjects
S F Man
Publications and source records attributed to S F Man.
Multiple spin echo imaging and quantitative relaxation measurements of pulmonary edema.
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Animals↗
Metabolic and hormonal responses in theophylline-increased cold resistance in males.
The effects of theophylline (a phosphodiesterase inhibitor-adenosine receptor antagonist) and substrate feeding (Ensure, 250 kcal/235 ml) on cold resistance were studied in seminude males undertaking submaximal (50% maximum O2 consumption), intermittent (34% of total time) exercise in the cold (-5 to 15 degrees C, individually adjusted) for 3 h. Each subject (n = 7) served as his own control and was tested on a weekly schedule. Under control treatment, rectal temperature (Tre) decreased by 0.9 degrees C to approximately 36.2 degrees C after cold exposure, whereas under theophylline and Ensure, the decrease of Tre was only 0.4 degrees C, indicating a significant increase (P less than 0.05) in cold resistance (50% better than control). The plasma concentration of theophylline was 4.8-5.9 micrograms/ml and was positively correlated with plasma concentration of free fatty acids. Plasma norepinephrine (NE) increased significantly during cold exposure; the absolute concentration was significantly higher after theophylline pretreatment. The plasma concentrations of glucose, epinephrine, cortisol, and adenosine 3',5'-cyclic monophosphate did not change and the changes of free thyroxine and triiodothyronine were minor. Together, the effectiveness of theophylline + Ensure in acutely increasing cold resistance may be due to increased substrate availability for thermogenesis, part of which, through theophylline's potentiation of both sympathetic release of NE and NE-stimulated lipolysis and part of which, through supplementary feeding of Ensure.
Adult↗
High-frequency oscillatory ventilation increases canine pulmonary epithelial permeability.
To investigate the effect of high-frequency oscillatory ventilation (HFOV) on the pulmonary epithelial permeability, we measured the clearance rate of nebulized sodium pertechnetate (99mTcO4-) and diethylenetriaminepentaacetate (99mTc-DTPA) before and after a 4-h period of mechanical ventilation in anesthetized mongrel dogs. The animals also underwent experiments with 4 h of spontaneous breathing (SB) and intermittent positive-pressure ventilation (IPPV) with and without addition of positive end-expiratory pressure (PEEP) for comparison. After IPPV and SB there was no change in the clearance rate of either 99mTcO4- or 99mTc-DTPA. After IPPV + PEEP and HPOV (8 and 16 Hz), there was an increase in the clearance rate of 99mTc-DTPA, but an increase in clearance rate of 99mTcO4- was seen after IPPV + PEEP only. In a separate group of dogs an increase in end-tidal lung volume was demonstrated after 4 h of ventilation with IPPV + PEEP (but not after HFOV), and this may account for the measured increase in 99mTcO4- clearance. We conclude that an increase in 99mTc-DTPA clearance rate after HFOV signifies an increase in pulmonary epithelial permeability, possibly through the mechanism of damage to the intercellular junctions during HFOV.
Animals↗
Effects of irradiation on canine tracheal epithelium: a physiological and morphological correlate.
We delivered 20 Gy irradiation in one fraction to a 6 cm segment of trachea in 11 dogs. Tracheal mucous transport was studied before and whenever possible at weekly intervals after irradiation using a gamma camera system and 99m technetium labeled sulfur colloid. Ten of the eleven animals were sacrificed at three different time intervals (1-2, 15-16 and 30-34 weeks) post-irradiation, and the tracheal epithelium removed for studies using Ussing chambers followed by preparation for microscopic analysis. Mucous transport along the length of the trachea was normal before irradiation, but following irradiation it became abnormal in the irradiated zone. Compared to the epithelium from the cranial and caudal segments, the irradiated epithelium had similar bioelectric measurements (potential difference, short-circuit current and resistance) and mannitol permeability. Also, the changes in the bioelectric measurements following indomethacin (10(-6) M) and epinephrine (10(-6) M) used sequentially, were similar in both the control and irradiated tissues. Scanning electron microscopic analysis of the irradiated zone revealed patches of nonciliated epithelial cells among the ciliates. We conclude that irradiation caused a persistent replacement of ciliated cells with nonciliates throughout the entire study period and that this alteration impaired mucous transport but did not affect epithelial ion secretion or barrier function.
Animals↗
Evaluation of the lung uptake of iodine-131 HIPDM by the single-pass multiple indicator dilution technique in a rabbit model.
The first-pass lung uptake of [131I]HIPDM was studied in a rabbit model using a conventional single-pass multiple indicator dilution (SPMID) technique with [99mTc]HSA as the intravascular marker. Lung extraction of [131I]HIPDM determined by the SPMID method was saturable, decreasing from 89.5 +/- 5.8% (mean +/- s.d., n = 4) at 4 nmol kg-1 to 63.8 +/- 6.2% at 1.5 X 10(4) nmol kg-1 relative to the intravascular tracer. The first-pass extraction of [131I]HIPDM derived from gamma-camera emission imaging data correlated well (R = 0.834) with simultaneously derived SPMID data. The extraction efficiencies were 94.4 +/- 3.3 and 87.9 +/- 3.2 at 200 nmol kg-1 and 68.0 +/- 6.2 and 64.0 +/- 10.7 at 1 X 10(4) nmol kg-1 (n = 4) for the SPMID and gamma-camera methods, respectively. Analysis of the lung arterial effluent blood indicated that no appreciable de-iodination or metabolism of [131I]HIPDM, within the limits of detection, occurred during the first pulmonary transit.
Animals↗
Effects of sulfur dioxide on pore populations of canine tracheal epithelium.
The bioelectric and barrier properties of the tracheal epithelium in nose-breathing dogs and in dogs that had been exposed for 75 min to compressed air or to two high concentrations of SO2 were measured and compared. We also studied tissues that had been treated with chloroform. Based on a model of restrictive diffusion we demonstrated heteropores (6 and 250 A) in the control tissues. Bioelectric changes due to 100-ppm SO2 were minimal. After exposure to 500 ppm SO2, adverse changes in the bioelectric properties were focal; they were marked in 8 out of 12 animals but were less striking in the other 4. Nonelectrolyte permeability increased with an increase in SO2 concentrations. Small pores were still present in the tissues severely affected by SO2 but they were absent in chloroform-treated tissues. Scanning electron microscopy of tissues from animals exposed to 500 ppm SO2 showed that in the same dog tissue appearance varied from normal to one of repair (normal bioelectric properties) or one of marked exfoliation of ciliated cells (abnormal bioelectric measurements).
Animals↗
Altered pulmonary epithelial permeability in canine radiation lung injury.
A radioaerosol scanning technique measuring regional clearance of sodium pertechnetate (99mTcO-4) and 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA) was used to assess changes in canine pulmonary epithelial permeability following lung irradiation. Doses of 2,000 cGy (11 dogs), 1,000 cGy (2 dogs), and 500 cGy (2 dogs) were given in one fraction to either the entire right hemithorax (500 cGy) or the right lower lung (1,000 and 2,000 cGy). Radioaerosol scans, chest roentgenograms, and computerized tomograms (CT) were obtained before and serially after irradiation. A dose of 2,000 cGy resulted in a decrease in regional pulmonary epithelial permeability to both 99mTcO4- and 99mTc-DTPA; both showed significant decreases from the 2nd wk postirradiation onward. In comparison, CT and chest roentgenogram did not become abnormal until 7.1 +/- 2.8 (SD) and 8.2 +/- 2.6 wk, respectively. Doses of 1,000 and 500 cGy produced reversible decreases in 99mTcO4- clearance. Lung morphology showed definite changes of radiation pneumonitis after 2,000 and 1,000 cGy but not after 500 cGy at approximately 9, 17, and 12 wk postirradiation, respectively. These results suggest that dose-dependent changes in pulmonary physiology may precede obvious structural alterations in radiation lung injury.
Aerosols↗
The effect of high frequency oscillatory ventilation on pulmonary stretch receptors in the dog.
High frequency oscillatory ventilation is a form of artificial ventilation where the tidal volume is less than the anatomical dead space. The efficacy of gas exchange depends upon the oscillatory frequency, volume, bias flow and the airway pressure. The present study was undertaken to determine the influence of oscillatory frequency, oscillatory volume and mean airway pressure upon the activity of pulmonary stretch receptors and rapidly adapting receptors during high frequency oscillatory ventilation. The experiments were conducted on dogs anaesthetized with either chloralose or nembutal. In Series I (16 slowly adapting stretch receptors) the effects of changing in turn, the oscillatory frequency, oscillatory volume and mean airway pressure were examined. The bias flow was held constant. Significant changes in the frequency of discharge of slowly adapting stretch receptors occurred only with alterations in oscillatory frequency (8,16,28 Hz) and mean airway pressure (3, 6 & 9 cm H2O). No significant changes in the activity of slowly adapting stretch receptors were observed when the oscillatory volume was altered (2.5, 5.0 & 7.5 ml/kg). With each manoeuvre there were significant small increments in intrathoracic gas volume. In Series II (16 slowly adapting stretch receptors) the interaction between oscillatory frequency and mean airway pressure was studied. The effect of each was greatest at the lowest value of the other variable. In Series III the effect of changing oscillatory frequency on the discharge from rapidly adapting receptors were examined. It was found that changes in frequency at a fixed airway pressure (3 cm H2O) and oscillatory volume failed to alter the activity significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
Action Potentials↗
Alveolar transfer of prostaglandin E2 in isolated perfused guinea pig lungs.
Alveolar transfer of prostaglandin E2 (PGE2) was characterized in isolated perfused guinea pig lungs (n = 19) by measuring radioactivity appearing in the venous effluent during 30 min after intratracheal instillation of [3H]PGE2, [14C]-mannitol, and [125I]iodoantipyrine. Recovery of lipid-soluble [125I]iodoantipyrine [91 +/- 3% (SE)] after 30 min was used to estimate total 3H and 14C delivered to the exchanging region of lung at time 0. In seven control lungs, 58 +/- 4% of [14C]mannitol and 16 +/- 4% of [3H]PGE2 was retained 10 min after instillation. Neither perfusion with diphloretin phosphate (10 micrograms/ml; n = 4) nor hypothermia (5 degrees C; n = 5) significantly affected the amount of [14C]mannitol retained; however, [3H]PGE2 remaining in these lungs increased significantly to 36 +/- 4 and 53 +/- 2%, respectively. Addition of unlabeled PGE2 (200 micrograms) to the instilled solution (n = 3) increased retention of both [14C]mannitol (80 +/- 3%) and [3H]PGE2 (65 +/- 4%). Alveolar transfer of [3H]PGE2 was calculated as the difference in percent retention of [14C]mannitol and [3H]PGE2 and normalized to that of [14C]mannitol. After 10 min, alveolar transfer of [3H]PGE2 was 71 +/- 8% in control lungs but was decreased to 26 +/- 7, 10 +/- 5, and 19 +/- 6% by diphloretin phosphate, hypothermia, or unlabeled PGE2, respectively. These data suggest that alveolar clearance of PGE2 involves a saturable drug- and temperature-sensitive process.
Animals↗
Characteristics of pertechnetate movement across the canine tracheal epithelium.
Several 99mTechnetium-labeled markers have been used to study the barrier properties of the pulmonary epithelium; among these compounds is sodium pertechnetate (TcO4-). As TcO4- has pseudohalide properties, and as the characteristics of the movement of this ion across the airway epithelium are unknown, we examined its bidirectional permeability coefficients, and compared them with those of radiolabeled Cl- and mannitol in canine tracheal epithelium in vitro. We found that this ion behaves similarly to Cl- in its translocation across the airway epithelium.
Animals↗
Effect of ethanol on intestinal uptake of fatty acids, fatty alcohols, and cholesterol.
The effect of acute exposure of the rabbit jejunum to ethanol on the uptake of fatty acids, fatty alcohols, and cholesterol was examined using a previously validated in vitro technique. The effective resistance of the intestinal unstirred water layer was determined from the rate of uptake of a homologous series of fatty alcohols. The addition of ethanol to the incubation or preincubation solutions had no effect on the uptake of these probes when the bulk phase was stirred at 600 rpm, but uptake was higher in the ethanol-exposed samples when the bulk phase was unstirred. Increasing the concentration of ethanol in the bulk phase was associated with a progressive decline in the rate of uptake of acetic, lauric, myristic, and palmitic acids, whereas the uptake of hexanoic, octanoic, and decanoic acids was unaffected, and the uptake of cholesterol was increased. Acute exposure of the intestine to ethanol was associated with an increase in the electrical conductance of the tissue, with no associated change noted in the tight junctions on transmission electron microscopy or in the surface epithelium on scanning electron microscopy. The results suggest that acute exposure of the rabbit intestine to ethanol is associated with a selective decline in the passive permeability properties of the membrane towards only certain lipids and that the effective resistance of the unstirred layer is influenced by ethanol only when the bulk phase is unstirred and the resistance is high.
Animals↗
Asymmetry of canine tracheal epithelium: osmotically induced changes.
The symmetry of osmotic conductivity of the canine tracheal epithelial cells was examined in vitro. When an osmotic load of 100 mosM sucrose was added to the serosal bathing solution, no change in the transepithelial potential difference was observed in 15 tissue preparations. In contrast, when the same osmotic load was added to the mucosal bathing solution, there was a rapid decrease in the transepithelial potential difference of 3.9 +/- 0.5 mV (n = 23); ouabain (10(-4) M) eliminated this change. Tissues that had been exposed to the osmotic load added to either the mucosal or serosal side were compared with the control using light and electron microscopy. When the osmotic load was added to the mucosal fluid, there was no change in the nuclear-to-cytoplasmic area ratio of the cell types examined. However, when the same osmotic load was added to the serosal fluid, a marked increase in the nuclear-to-cytoplasmic area ratio of the ciliated cells was observed. This finding indicated cell shrinkage. Dilution potentials measured by substituting NaCl with mannitol also showed asymmetry. The morphological features are probably caused by differences in the osmotic conductivity (Lp) of the basolateral and apical cell membranes, with the Lp of the apical membrane being less than that of the basolateral membrane. The basis for osmotically induced potentials remained undetermined.
Animals↗
Relationship between regional ventilation and aerosol deposition in tidal breathing.
The regional distribution of the deposition of 1.2 micron particles of 99mTc sulfur colloid inhaled by tidal breathing was compared with the distribution of ventilation as measured by a 133Xe washout technique. Twelve subjects were studied, 6 with normal pulmonary function tests, 5 with air-flow limitation, and 1 with unilateral phrenic nerve paralysis. Both xenon and aerosol were inhaled at tidal volume by the subjects while seated upright. A large field gamma camera acquired posterior scans. Thirteen experiments were also done on 7 dogs: 1 with extrathoracic obstruction of the airway to 1 lung, and 12 with bronchoconstriction from the instillation of methacholine chloride into the airways of a lower lobe. Two of these dogs were studied with a gamma camera system, and the others were studied with a Picker multi-probe system. Both in humans and in dogs, an increase in time constant, which indicated a decrease in ventilation, was associated with an increase in peripheral aerosol deposition when normalized for ventilation. It is suggested that the increased residence time is responsible for the increased deposition in regions that received lesser ventilation.
Adult↗
Single photon emission tomography of lungs imaged with 99mTc-labeled aerosol.
The use of single photon emission computed tomography (SPECT) and radiolabeled aerosols for lung scanning offers theoretical advantages over conventional gamma camera imaging. We verified the feasibility of using such a system to define particle deposition. First, in two dogs, we detected segments of the lung which had received fewer radiolabeled particles because of obstruction to the airway by a balloon or a lead shot. Second, by comparing axial computed tomography (CT) images to their SPECT counterparts, we were able to demonstrate the effectiveness of SPECT in delineating large thoracic structures such as major vessels and central airways. We feel that SPECT also provides excellent images for qualitative work. We then used SPECT to study aerosol deposition in 13 normal subjects and eight patients. We found that the normal subjects had uniform peripheral deposition, but the eight with abnormal lung function had patchy deposition. Furthermore, we found that regions of abnormal deposition not seen on conventional views could be delineated by tomography. We conclude that this technique will improve our understanding of aerosol deposition in humans by providing a three-dimensional visualization of the lungs and airways.
Aerosols↗
Re: Mucociliary clearance mechanism in smoking and nonsmoking normal subjects.
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Cilia↗
Exercise impairment in chronic obstructive pulmonary disease.
This article reviews factors that may limit exercise performance in patients with COPD. These factors include alteration in pulmonary mechanics, respiratory muscle fatigue, impairment in pulmonary gas exchange, abnormal perception of breathlessness and ventilatory control, cor pulmonale, and poor nutritional status. The clinical application of exercise testing in patients with COPD and the role of various therapeutic modalities in altering exercise performance in COPD are discussed.
Diaphragm↗
Nutrient intake of patients with cystic fibrosis.
Nutrient intake, anthropometric measurements, and pulmonary function were assessed in 26 young adult patients with cystic fibrosis (CF). Mean nutrient intakes, excluding those from vitamins and nutrient supplements, were less than the Recommended Dietary Allowances for folate for men and women and for iron and vitamin B-6 for women. Male cystic fibrosis patients consumed significantly more of 11 of 16 nutrients in comparison with men with Crohn's disease and men with functional gastrointestinal complaints. Female cystic fibrosis patients consumed significantly more of 9 of 16 nutrients than did women with gastrointestinal complaints. The relative body weight was less than 85% of standard in 65% of men and 50% of women with CF. Relative body weight was correlated with variables indicative of airflow obstruction, reduced vital capacity, and hyperinflation of lung volumes.
Adolescent↗