Rodney A. Rhoades

Long-term nitrogen dioxide exposure: effects on lung lipids and mechanical properties.

Male Long Evans hooded rats were chronically exposed to an average 2.9 ppm (±0.71 SD) of nitrogen dioxide 24 hours each day, five days a week for nine months. The major effects of NO2 were a significant 12.7% increase in lung wet weight, a 13.0% decrease in lung compliance, and a significant reduction in surface-active properties of the lung wash. The NO2-exposed lungs also revealed a significant 8.7% decrease in lung lipid content and a marked decrease in percentage of total saturated phospholipid fatty acids. This reduction in saturation was due almost entirely to a decrease in the percentage of palmitic acid. The suggestion is made that alterations in lung lipid metabolism may be the underlying mechanism which leads to some of the pulmonary effects following long-term exposure to subacute levels of NO2.

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

The effects of circulating levels of glucose and palmitate in the isolated perfused rat lung were investigated. Rat lungs were perfused for 1.5 hr with washed bovine erythrocytes (15% hematocrit) in Krebs-Henseleit bicarbonate buffer containing 5 g% bovine serum albumin. Glucose uptake in the perfused lung varied directly with circulating glucose concentration. Lactate production was affected proportionately more by high glucose levels than by low concentrations. Pyruvate production was decreased by both low glucose and palmitate concentration in the circulating medium. Oxidation of glucose to CO2 was depressed by low glucose and by high palmitate concentrations. Glucose incorporation into lung lipids was more strongly influenced by glucose concentration than by circulating palmitate levels. These data indicate acute changes in circulating levels of glucose and palmitate alone can act to either inhibit or stimulate glycolysis, glucose oxidation, and lipid synthesis in the perfused lung.

Quantitative recovery of phospholipids from alveolar wash.

Abstract Modifications and standardization of an alveolar perfusion technique, and normal alveolar phospholipid concentrations of rats are reported. The presence of surface active material in the alveolar wash was demonstrated by marked hysteresis loops, and maximum and minimum surface tensions of 43.4 (1.6 S.D.) and 1.6 (0.4 S.D.) dyne/cm, respectively, from surface tension-area measurements. Lipid analysis revealed a phospholipid distribution similar to that obtained from other species and/or methods. Phosphatidyl choline accounted for 79% of the total phospholipid. Phospholipid concentration in lung washings of eleven rats was 2.4 (0.48 S.D.) μg mg lipid mg dry lung The described method of alveolar phospholipid recovery in consistent amounts for quantitative estimations may be useful for further characterization of the pulmonary surfactant system and its metabolism in health and disease. Advantages of the method are enumerated.

14C-1-palmitate incorporation by rat lung: effect of nitrogen dioxide.

Summary The effect of breathing nitrogen dioxide (NO2) on the in vivo incorporation and turnover of 14C-1-palmitate in rat lung lecithin was studied. Continuous exposure to 5 ppm of NO2 for 14 days markedly decreased lecithin turnover. The suggestion is made that changes in lecithin turnover may lead to alterations in the surface-active material on the alveolar surface which in turn may account for some of the damage observed in NO2-exposed lungs.

in vivo Incorporation of 14C-1-palmitate and 3H-U-glucose into lung lecithin☆

Abstract Incorporation of 14 C-1-palmitate and 3 H-U-glucose into lung lecithins was studied by injection of the doubly-labeled isotopic solution intravenously into fed and fasted (72 hr) rats. Radioactivity was measured in lecithins from whole-lung homogenates as well as the hydrolytic products of these lecithins (fatty acid and glyceride-glycerol fractions) at 1, 2, 6, 15 and 24 hr after intravenous injection. Biological half-life of lecithins from control animals was calculated to be 12 hr and 11 hr for 14 C- and 3 H-decay curves, respectively. Fasting did not significantly alter the half-life of whole-lung lecithins. Hydrolysis of lecithins and analysis of the 14 C-labeled fatty acid and 3 H-labeled glyceride-glycerol fractions yielded similar half-lives for these moieties, indicating that the lung phosphatide is being turned over as an entity.

Fetal Rat Lung Development: Lipids and Surface Tension Properties After Decapitation in utero

Summary Decapitation in utero produces hormonal deficiencies which do not influence lung organogenesis but retards pneumocyte differentiation at the organelle and molecular levels. Such lungs contain decreased quantities of phospholipid and functionally are impaired in their ability to reduce surface tension to normal levels. The mechanisms by which these alterations are produced are most likely related to hormonal deficiencies during fetal development. These deficiencies may specifically alter lung phospholipid metabolism. Retardation of phospholipid metabolism may, however, be secondary to a more generalized retardation of pneumocyte differentiation. We favor the latter hypothesis in so far as pituitary failure occurring in man and animals with fully mature lungs does not lead to clinical respiratory distress (33, 38). Further inquiry into the manner in which hormones influence lung metabolism will require evaluation of the effect of specific hormonal replacements on in utero decapitated or hypophysectomized fetuses and on lung explants differentiating in vitro.

Characterization of lung geometry from the single-breath nitrogen washout test

Abstract A previously developed transport analysis was used to simulate two sets of single-breath nitrogen washout data from each of four normal subjects. The analysis treats simultaneous gas flow and longitudinal diffusion and incorporates a modified form of Weibels anatomical model “A” to describe the airway geometry. For each data set, four geometric parameters of the analysis were varied in a computer simulation until it matched the instantaneous expiratory concentration curve; particular emphasis was placed on matching the data in the concentration transition. Monitored values of functional residual capacity and instantaneous respiratory flow were supplied as inputs to each simulation. For each subject, a reasonable computer simulation could be obtained using a single set of lower airway geometric parameters, even though the average respiratory flow rate varied by as much as 53% from test to test; this result is due to the ability of the transport analysis to directly account for gas mixing during normal respiration. Under the same conditions the anatomic dead space varied by as much as 24%.

Influence of adrenalectomy on the rat lung.

Summary Glucose-U-14C, glucose-1-14C, and glucose-6-14C utilization were examined in vitro in lungs from adrenalectomized (ADX) male rats. Lungs from rats killed 3 weeks following adrenalectomy showed a significant increase (P < 0.05) in lung weight. Incorporation of glucose-U-14C by the lung was significantly depressed by 30% in total lipids and by 32% in phospholipids (PL) in the ADX group. Hydrolysis of PL revealed that the depressed incorporation was proportionately greater in PL fatty acid than in PL glyceride glycerol moiety. The ability to oxidize labeled glucose was also significantly reduced (26%) in the ADX lungs. The C1/C6 ratio was significantly lower in the ADX group, suggesting relatively less carbon flow through the hexose monophosphate shunt. The data shows that adrenal deficiency has a profound influence on glucose metabolism and lipogenesis in the rat lung. Adrenalectomy did not affect lung surface tension properties. The suggestion is made that following adrenalectomy there is an increase in amount of growth hormone or an increase sensitivity to normal secretions of growth hormone which leads to higher lung weight and altered carbohydrate metabolism. A sincere thanks is extended to Mary Lou Eskew for her technical assistance.

Influence of inhaled carbon particulates on pulmonary surface area.

Summary Pulmonary surface area was significantly reduced in rats chronically exposed to low levels of carbon particulates (545 μg/m3, μ 193 SD) for 9 months. The decrease in surface area was much more pronounced at lower lung volumes. The suggestion is made that the reduction in lung surface area is related to terminal airway obstruction. Thanks are extended to Mary Lou Eskew, Ronald Perrone and Anthony Wisbith for their technical assistance (CAES Publ. No. 217–72.)