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Biomedical subjects

R R Mercer

Publications and source records attributed to R R Mercer.

35 records · Page 2Linked to original sources
PubMed1989

Postnatal growth of pulmonary acini and alveoli in normal and oxygen-exposed rats studied by serial section reconstructions.

Three-dimensional reconstructions from serial sections were used to examine postnatal lung development of rats reared in air (control) or oxygen. From birth to age 21 days, control lung volume increased ninefold, and the average volume of each ventilatory unit (all airspaces distal to a single respiratory bronchiole) increased seven times. There were approximately 5,000 ventilatory units at birth and on day 21, indicating that the lung grew by enlargement and subdivision of ventilatory units and not by their multiplication. Growth in hyperoxia (greater than 97%) for 7 days had no effect on the number of ventilatory units but, compared to controls, total lung volume and ventilatory unit volume were reduced 32% and 16%, respectively. At birth there were 0.6 x 10(6) alveoli, and at age 7 days in controls alveolar number increased 16-fold while the average volume of a single alveolus fell to one-sixth that at birth. Exposure to hyperoxia for 7 days stopped alveolarization; the surface area to volume ratio (Sa/V) of the ventilatory unit was lower, alveolar number was the same as at birth, and the alveoli present were large. At age 21 days, after 14 days of recovery in air, lung volume and ventilatory unit volume were greater than in controls but the Sa/V of the ventilatory unit was still depressed 20%. Alveoli from oxygen-exposed lungs were larger than in controls, and a greater size distribution coefficient showed them to be more variable. A shape coefficient for alveoli did not change as a function of the animal's age or oxygen treatment; it demonstrated proportional growth of alveolar height and diameter.

Animals↗
PubMed1988

Effects of low levels of NO2 on terminal bronchiolar cells and its relative toxicity compared to O3.

This report describes structural changes occurring in the terminal bronchioles of rats exposed to low levels of NO2 continuously for 6 weeks. In addition, the relative susceptibility of epithelial cells to oxidants and the comparative toxicity of NO2 and O3 are discussed. Terminal bronchioles isolated from rats exposed 5 days/week to 2.0 ppm NO2 (plus two 1-hr daily spikes to 6.0 ppm) were found to have 19% less ciliated cells per unit area of epithelial basement membrane. The remaining ciliated cells had a reduced mean surface area (-29%). The shape of the Clara cell changed with reduced size of the dome protrusions but increased cell contact with the basement membrane. These data indicate that exposure to 2.0 ppm NO2 (+ spikes) for 6 weeks caused injuries to cilia and ciliated cells and possible Clara cell differentiation in the terminal bronchioles of adult rats. Exposures of adult or juvenile rats to 0.5 ppm NO2 (+ two 1-hr daily spikes 5 days/week to 1.5 ppm) did not cause morphologically measurable injuries in the terminal bronchioles. The severity of the concentration-dependent epithelial cell reactions to NO2 and O3 in adult rat terminal bronchioles were compared to those occurring in the proximal alveolar regions (PAR). Epithelial cells in the PAR appeared to be more susceptible to oxidant insult since both 0.5 ppm NO2 and 0.25 ppm O3 were found to cause epithelial injury only in the PAR. Comparison of epithelial reactions to 6-week exposures to either NO2 or O3 indicated that 0.25 ppm O3 caused four times as much increase in the number of type I epithelial cells as did 2 ppm (+spikes) NO2. Therefore, O3 could be 40 times more toxic than NO2 in the PAR on the basis of the inspired concentration and the focal response. On the other hand, there was no loss of ciliated cells following the 0.25 ppm O3 exposure. This suggests that the ratio of O3 to NO2 toxicity in the terminal bronchioles is considerably less than 10. The relative toxicity of the two oxidant gases appears to be site specific.

Animals↗
PubMed1988

Evaluation of lung diffusing capacity by physiological and morphometric techniques.

Determinations of pulmonary diffusing capacity for CO (DLCO) by physiological and morphometric techniques have resulted in substantially different values for both DLCO and its major components. To evaluate the differences in these methods of measurement of DLCO, measurements were made under controlled conditions on isolated perfused dog lungs. Multiple gas-rebreathing techniques were used to measure DLCO, the membrane component of the diffusing capacity for CO (DmCO), and pulmonary capillary blood volume (Vc) in both anesthetized dogs and after isolation and perfusion of their lungs. The isolated perfused lungs were than perfusion fixed for morphometric analysis of the components of DLCO. The values obtained morphometrically for Vc were similar to those measured by physiological techniques. Perfusion fixation did not substantially alter the morphometric estimate of DmCO when compared with previous values obtained on inflation fixed lungs. However, the morphometric estimate of DmCO was over 10 times higher than that estimated physiologically. Analysis of the potential errors in the techniques suggests that the correct value for DmCO is substantially higher than that commonly estimated by use of physiological techniques and that the explanation for the difference is due to a number of factors that can influence the binding of CO to hemoglobin under in vivo conditions. The net effect of these factors can be represented by an unknown in each component of the Roughton-Forster relationship so that 1/DL = 1/(U1.Dm) + 1/(U2.theta Vc), where theta is the binding rate for CO to hemoglobin. Because the magnitudes of the unknown terms (U1 and U2) in the Roughton-Forster relationship are likely to be large, this relationship cannot be reliably used to determine Dm and Vc.

Animals↗
PubMed1988

Effects of inhalation of 0.25 ppm ozone on the terminal bronchioles of juvenile and adult rats.

Cells of the terminal bronchioles are particularly susceptible to the effects of inhalation of low levels of ozone (O3). One-day-old (juvenile) or 6-week-old (adult) rats were exposed to 0.25 ppm O3 for 12 h/day or to continuous room air for 6 weeks. Morphometric analysis of perpendicular cross sections of terminal bronchioles demonstrated that exposure to O3 produced alterations in the surface characteristics of ciliated and nonciliated (Clara) cells in both groups of rats. There were significant losses (20-30%) of the surface area contributed by cilia and the luminal surface of Clara cells was decreased by 16-25%. O3 exposure also produced significant decreases in the number of brush cells per square millimeter of terminal bronchiolar basement membrane. The results of this study indicate that the normal structure of terminal bronchiolar epithelial cells is significantly altered by inhalation of 0.25 ppm O3. No statistically significant interactions between the effects of O3 and animal age at the beginning of the exposure were found.

Aging↗
PubMed1987

Three-dimensional reconstruction of alveoli in the rat lung for pressure-volume relationships.

To determine alveolar pressure-volume relationships, alveolar three-dimensional reconstructions were prepared from lungs fixed by vascular perfusion at various points on the pressure-volume curve. Lungs from male Sprague-Dawley rats were fixed by perfusion through the pulmonary artery following a pressure-volume maneuver to the desired pressure point on either the inflation or deflation curve. Tissue samples from lungs were serially sectioned for determination of the volume fraction of alveoli and alveolar ducts and reconstruction of alveoli. Alveoli from lungs fixed at 5 cmH2O on the deflation curve (approximating functional residual volume) had a volume of 173 X 10(3) microns3, a surface area of 11,529 microns2, a mouth opening diameter of 72.7 microns, and a mean caliper diameter of 91.8 micron (SE). Alveolar shape changes during deflation from total lung capacity to residual volume was first (30 to 10 cmH2O) associated with little change in the diameter of the alveoli (102.7 +/- 2.4 to 100.3 +/- 3.3 microns). In the range overlapping normal breathing (10 to 0 cmH2O) there was a substantial decrease in diameter (100.3 +/- 3.3 to 43.3 +/- 2.3 microns). These measurements and others made on the relative changes in the dimensions of the alveolus suggest that the elastic network, particularly around the alveolar ducts, are predominant in determining lung behavior near the volume expansion limits of the lung while the elastic and surface tension properties of the alveoli are predominant in the volume range around functional residual capacity.

Animals↗
PubMed1987

Three-dimensional reconstruction of the rat acinus.

This study provides a quantitative description of the small airways and alveolar duct-alveolar architecture of the rat lung. To accomplish this, quantitative three-dimensional reconstructions were made of small airways, the alveolar duct system, and alveoli. The branching pattern of the small airways immediately proximal to the alveolar ducts varied significantly. For example, the number of bronchiole-alveolar duct junctions per parent bronchus (terminal bronchiole) ranged from two to six. The number of bronchiole-alveolar duct junctions per lung was 7,280 +/- 250 (mean +/- SE). The general shape of the ventilatory unit arising from each bronchiole-alveolar junction was that of a space-filling sphere with an outer diameter of 1,490 +/- 130 microns. The average distance from the bronchiole-alveolar duct junction to alveoli at the end of the alveolar sac termination was 1,290 +/- 100 microns. Numerous trifurcations were found in the branching pattern of the alveolar ducts. The branching of the alveolar ducts did not fit a regular dichotomous pattern. The volume of the terminal branches (alveolar sacs) accounted for 64 +/- 5% of the volume of the ventilatory unit. Both of these factors, the pattern of branching and the substantial volume distributed in the most peripheral branches, contribute to the uniform distribution of gas within the ventilatory unit and thus minimize potential diffusion limitations to gas exchange.

Animals↗
PubMed1986

Differential distribution of brush cells in the rat lung.

The distribution of brush cells in the rat lung was studied using electron microscopic morphometry. Samples were taken from six distinctive anatomical regions. Tissue from the trachea, lobar bronchi, terminal bronchioles, first alveolar duct bifurcations, proximal alveolar regions, and the distal alveolar region were isolated and embedded in Epox 812. Aside from the trachea and the lobar bronchi, the other four regions were isolated from embedded tissue using microdissection techniques. Electron micrographs taken from thin sections of these samples were analyzed. It was found that brush cells made up 10% of the volume of epithelium covering the first alveolar duct bifurcation. Approximately 2% of the proximal alveolar epithelium, 1.4% of the terminal bronchiolar epithelium, and 3% of the tracheal epithelium were made up of brush cells. No brush-bordered epithelium was found in the lobar bronchi or in the distal alveolar walls. We conclude that brush cells have a distinct spatial location in the lung, being in high concentration in the trachea and in areas where first generation alveolar ducts bifurcate. The highest density was on the bifurcation of the first alveolar ducts, and their density decreased radially from this region.

Animals↗
PubMed1986

Airway branching patterns influence asbestos fiber location and the extent of tissue injury in the pulmonary parenchyma.

The degree to which various anatomic components of the lung influence the distribution of inhaled particles is not entirely clear. Therefore, we have studied the role intrapulmonary airways play in the localization of respired asbestos fibers and have correlated local asbestos fiber burden with tissue injury in rats following exposure to aerosolized chrysotile asbestos for 7 hours per day, 5 days per week for 12 months. Tissues arising from anatomically distinct pathways of the tracheobronchial tree were isolated by using microdissection. Adjacent tissue blocks from regions immediately distal to the last dissected airway were prepared for light microscopic evaluation or digested in hypochlorite solution to determine alveolar septal tissue density and asbestos fiber concentration respectively. These studies demonstrated regional differences in asbestos fiber number, size, and mass which were inversely related to airway pathlength and to bifurcation number along each airway path. Fiber burden within each region was found to be proportional to the relative degree of tissue injury present. These findings suggest that differences in tissue injury from region to region in the lungs following exposure to asbestos are a result of regional differences in the deposition and retention of these substances in the lungs. These airway characteristics which influence fiber deposition may also play an important role in the deposition and subsequent lung injury caused by other particulates and environmental pollutants.

Animals↗
PubMed1985

Inhalation studies of Mt. St. Helens volcanic ash in animals: respiratory mechanics, airway reactivity and deposition.

Effects of fine volcanic ash aerosol on pulmonary mechanical properties of awake guinea pigs were evaluated during exposure by inhalation. Ash penetration into the lung as well as tissue response to ash were determined by transmission electron microscopy. The reactivity of airway epithelial irritant receptors following ash exposure was assessed using a histamine bronchoprovocation test. Results indicated that breathing 9,4 mg/m3 of ash for 2 hr did not cause a measurable change in pulmonary function of guinea pigs. Electron micrographs showed that ash particles in the lung below the hilus did not seem to produce any acute tissue reaction and were almost all phagocytized by macrophages. Airways of guinea pigs exposed to ash were significantly less responsive to histamine than were the airways of animals exposed only to air. It appears that even though Mt. St. Helens ash was well tolerated by the guinea pig during the exposure, its presence in the inhaled air did change the "histamine sensitivity" of airway epithelial irritant receptors.

Air Pollutants↗
PubMed1985

Inhalation studies of Mt. St. Helens volcanic ash in animals. II. Lung function, biochemistry, and histology.

Rats were exposed by inhalation to 9.4 mg/m3 size-fractionated volcanic ash for 5 days (2 hr/day) and examined for changes in pulmonary function and histology for periods of up to 1 year. Fine-mode volcanic ash, SO2, and a combination of ash and SO2 produced no observable effects in normal rats and rats with elastase-induced emphysema. However, there was a mild irritant response to SO2 which was not influenced by the volcanic ash. Rats injected intratracheally with fine-mode volcanic ash or saline showed no evidence of pulmonary alterations after 6 months. Those injected with coarse-mode volcanic ash showed minor pulmonary functional changes, histologically detectable alveolitis, and small increases in lung weight. In contrast, quartz-injected rats showed large alterations in pulmonary function, lung weight, hydroxyproline levels, and large areas of lung consolidation and fibrosis.

Animals↗
PubMed1985

The role of osteocytes in bone resorption during lactation: morphometric observations.

It has been suggested that osteocytes may resorb bone during the calcium mobilization that occurs during lactation. To test this hypothesis morphometric methods were used to evaluate changes in mature nonmated female rats, 6-day postpartum nonlactating rats, 21-day postpartum nonlactating rats, 6-day lactating rats, 15-day lactating rats, and 21-day lactating rats using femur cross sections in the diaphyseal region. Osteoclast resorption per unit length of periosteal surface, as well as other measures of resorption activity, demonstrated that by 15 days of lactation a significant mobilization of calcium was occurring. The volume density of osteocyte lacunae and individual lacunar volumes from serial section reconstruction showed no increase in the lactating groups. Indeed, the only significant change in lacunae volume was a decrease apparently due to pregnancy. It is concluded from this study that osteocytes do not resorb bone during lactation.

Animals↗
PubMed1984

Alterations in lung structure caused by inhalation of oxidants.

Morphometric and morphologic methods have been used to evaluate changes in rat lungs caused by the inhalation of a variety of oxidants. Exposure to 100% oxygen causes diffuse pulmonary injury and leads to death after 66-72 h of exposure. The primary insult leading to death in rats exposed to hyperoxia is injury to pulmonary capillary endothelium. Sublethal exposure to hyperoxia was found to cause diffuse injury to all major components of the alveolar septum and was associated with destruction of approximately 50% of the pulmonary capillary endothelial cells. A corresponding decrease in pulmonary capillary surface area and capillary lumen volume also occurred. Exposure to ozone and to nitrogen dioxide in low concentrations did not cause a diffuse injury throughout the alveolar region of the lung, but rather led predominantly to structural alterations in terminal bronchioles and in their adjacent alveoli. Morphometric evaluation of animals exposed to 0.25 ppm ozone and to 2 ppm NO2 demonstrated quantitatively and qualitatively similar lesions. These lesions primarily involve injury and remodelling of the alveolar epithelium. These changes in the alveolar epithelium were also associated with the recruitment of increased numbers of alveolar macrophages to the proximal alveolar region. The different types of lung injury caused by various oxidants are most likely to be related to differences in their reactivity with tissue components and to differences in concentration, distribution, and diffusion characteristics of the oxidant gases.

Animals↗
PubMed1983

Effects of prenatal nitrofen exposure on postnatal lung function in the rat.

The herbicide Nitrofen was administered by gavage to pregnant F-344 rats during Days 10 through 13 of gestation. Postnatal lung function was measured in male progeny at 3 and 6 weeks of age. There were no differences in body weight or wet and dry lung weights between control and Nitrofen-exposed rats in either age group. Nitrofen produced no observable effects on lung function at 3 weeks of age. However, by 6 weeks of age the Nitrofen-exposed animals had significant decreases in tidal volume (p less than 0.01), vital capacity (p less than 0.01), total lung capacity (p less than 0.05), and quasi-static lung compliance (p less than 0.01). There was also a mild ventilation inhomogeneity, as indicated by significant increases in the nitrogen washout slope (p less than 0.01) and the moment ratio (p less than 0.05). Histopathology of lung, liver, kidney, and testes was not significantly altered by Nitrofen exposure. These data suggest that prenatal Nitrofen exposure may have an effect on postnatal lung maturation in the rat and could potentially be useful as a model of pulmonary hypoplasia.

Aging↗
PubMed1982

Oxygen consumption measured with microcomputer-assisted Warburg manometry.

We have developed and tested an automated system that measures in vitro oxygen consumption by Warburg manometry in as many as 16 units that are under the simultaneous control of a microcomputer which requires attention at the beginning of the study only. The all-glass Submarine Volumometers used are readily adapted to automation using a microcomputer that interacts with an infrared photodetector sensitive to manometric changes in the reaction vessel and a stepper motor that can advance the calibrated micrometer in response to these changes. The microcomputer interacts with the user at the start of the study during data entry and subsequently determines volume changes related to oxygen consumption, calculates respiration rates, and prints or graphs the results without further user interaction. We compared this automated system with manual methods by measuring the oxygen consumption of lung tissue slices and by determining the ability of the system to match known volumes entered manually. We found that the results obtained using the automated system were not significantly different from known manual methods (P less than 0.05).

Animals↗
PubMed1982

Dose response of elastase-induced emphysema in hamsters.

Elastase-induced emphysema in hamsters was studied using pulmonary function tests in an effort to develop techniques for determining the effects of air pollutants on the progression of this disease. Single intratracheal injections of 6, 12, or 24 units of porcine pancreatic elastase produced dose-related changes in pulmonary function after 4 wk when compared with sham-injected control animals. Boyle's law end-expiratory volume and residual volume, measured by gas dilution, increased (p less than 0.05) at 12 and 24 units, respectively, whereas vital capacity, determined plethysmographically, and total lung capacity wee increased (p less than 0.05) at all 3 elastase doses. Respiratory system compliance, calculated by a nonlinear least squares regression fit of the deflation pressure-volume curve, increased (p less than 0.05) at 24 units only. The multiple-breath nitrogen washout slope (N2 slope) and the single-breath diffusing capacity for carbon monoxide (DLCO) decreased (p less than 0.05) at all 3 doses of elastase. Both histologic and physiologic evaluation showed dose-related pulmonary impairment. It appears, therefore, that as little as 6 units of elastase produces mild emphysema in hamsters, which is detectable by pulmonary function testing. Of these tests, the DLCO and N2 slope were the most effective in detecting the degree of impairment.

Animals↗
PubMed1978

Servo control of end-tidal CO2 in paralyzed animals.

We are reporting an electronic circuit which uses the peak end-tidal CO2 signal from a rapid infrared CO2 analyzer to vary the motor rate of a fixed volume respirator. It contains variable gain and a lag compensation network which permits critical damping to prevent oscillation. The CO2 analyzer, circuitry, and respirator are connected in a closed-loop servo system that allows automatic control of the CO2 level. The system's gain and performance are such that it can accommodate large changes of CO2 return to the lungs with no more than +/- 0.5 Torr carbon dioxide pressure (PCO2) error signal. It has proved useful in experiments on neural respiratory control in paralyzed animals where it is desired to keep PCO2 constant despite changes in cardiac output and venous and CO2 return to the lungs, and to monitor the approximate magnitude of these changes.

Carbon Dioxide↗