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Biomedical subjects

D Massaro

Publications and source records attributed to D Massaro.

At least 91 records · Page 5Linked to original sources
PubMed1981

Surfactant aggregation in rat lungs: influence of temperature and ventilation.

We examined the effect of the ventilatory rate and the temperature of excised lungs and of increased body temperature of anesthetized spontaneously breathing rats on the centrifugal sedimentation of disaturated phosphatidylcholine (DSPC) present in lung lavage returns. More DSPC sedimented from lungs ventilated at low than at high rates, and sedimentation of DSPC and lung volume loss were temperature dependent, 41 greater than 37 greater than 4 degrees C. Most of the noncellular sedimented material was tubular and common myelin; these had diminished ability to lower surface tension rapidly compared with less-aggregated surfactant. More aggregated DSPC accumulated and lung volume decreased more in spontaneously breathing rats anesthetized for 30 min than in rats killed immediately after being anesthetized; these changes were greater after 30 min of anesthesia in hyperthermic rats (40.4 +/- 0.3 degrees C) than in normothermic rats (37.4 +/- 0.1 degrees C). These studies have shown a correlation between the increased accumulation of surfactant as large aggregates and the loss of alveolar stability; however, a cause and effect between these events has not yet been shown.

Adsorption↗
PubMed1981

Regulation of secretion in Clara cells: studies using the isolated perfused rat lung.

Previous studies from our laboratory indicated that both beta-adrenergic and cholinergic agents stimulate in vivo secretion by rat bronchiolar Clara cells. Those studies also provided support for an in-series beta-adrenergic-cholinergic stimulation of secretion. To further explore the regulation of secretion in Clara cells, and to do it in the absence of systemic influences, we have used the isolated ventilated perfused rat lung. We have again used morphometry and electron microscopy to assess secretion by measuring the volume density (fraction of cell volume) of the secretory granules of bronchiolar Clara cells. We found that in the isolated perfused lung, as in the intact animal, isoproterenol stimulated secretion in Clara cells and that this effect was blocked by the beta-adrenergic antagonist propranolol. Pilocarpine, unlike its action in the intact animal, did not stimulate secretion in the isolated lung; rather it inhibited the secretory effect of isoproterenol. Increased tidal-volume ventilation stimulated secretion; propranolol did not block this effect. Analogs of cyclic (c)AMP and of cGMP also stimulated secretion by Clara cells. These findings indicate that there are at least two mechanisms by which Clara cells can be stimulated to secrete. One seems to be beta-adrenergic-cAMP mediated but the triggering event is unknown. The other is initiated by increased tidal volume and cGMP may be involved in the intracellular mediation of this stimulatory event. Finally, we found evidence of beta-adrenergic (stimulatory) -cholinergic (inhibitory antagonism in the regulation of secretion in Clara cells.

Animals↗
PubMed1980

A hypothesis relating breathing pattern to some forms of the "adult respiratory distress syndrome".

Quantitative deficiency of surfactant in neonates results in hyaline membrane disease. Although surfactant is also required for normal gas exchange in adults, no disorders have been clearly attributable to a deficient amount of surfactant. Based on studies in our laboratories as well as on information and ideas in the literature, we suggest that a physical alteration in surfactant may lead to, or contribute to, the development of some forms of "adult" respiratory distress syndrome." In particular, we suggest that an altered breathing pattern contributes to the alveolar collapse and liver-like appearance of the lung found in certain clinical entities, i.e., pulmonary embolism and oxygen toxicity. We hypothesize that in these conditions shallow breathing leads to the aggregation of surfactant into a less functional form resulting in increased alveolar surface tension and atelectasis. The increase in surface tension would also contribute to the edema found in these conditions.

Humans↗
PubMed1980

Oxygen toxicity.

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Animals↗
PubMed1980

Effect of prenatal isoxsuprine on pulmonary oxygen toxicity in the newborn rat.

Isoxsuprine, a beta-sympathomimetic agent used clinically to delay premature parturition and to possibly accelerate fetal lung maturation, was administered to pregnant rats at 48 and 24 h prior to delivery. Newborn rats were placed in 96-98% O2 (or room air) to determine if the prenatal isoxsuprine treatment compromised their tolerance to prolonged hyperoxic exposure. (Exogenous catecholamines are known to exacerbate O2 toxicity in adult animals). Survival of the isoxsuprine-treated pups in O2 (52%) was no different than for control neonates exposed to hyperoxia for 7 days (57%) (P = 0.22). Body weight, lung weight, lung protein, and DNA content of the newborns were also not altered by the prenatal isoxsuprine treatment. Lung antioxidant enzyme activities for superoxide dismutase, catalase, and glutathione peroxidase were the same at birth in the isoxsuprine-treated and control rat pups, and the enzyme activities increased in response to hyperoxic exposure in each group to an equivalent degree. Thus, in utero treatment with isoxsuprine had no apparent adverse effect on newborn rats exposed to a prolonged O2 challenge.

Animals↗
PubMed1980

Potection from oxygen toxicity with endotoxin. Role of the endogenous antioxidant enzymes of the lung.

Endotoxin treatment of adult rats before hyperoxic exposure significantly increases their survival rate in >95% O(2) (J. Clin. Invest.61: 269, 1978). In this study, we wished to determine: (a) whether endotoxin would protect against O(2) toxicity if it were administered after the animals were already in >95% O(2) for 12-48 h; and (b) the relationship between the endogenous antioxidant enzymes of the lung and the protective effect of endotoxin treatment. Our results showed that adult rats given a single 500 mug/kg dose of endotoxin up to 36 h after the onset of O(2) exposure had significantly increased survival rates and decreased lung fluid accumulation compared to untreated animals in O(2) (P < 0.05). (Survival, 16/49 [untreated rats]; 18/20 [endotoxin at 12 h after the start of O(2) exposure]; 25/26 [endotoxin-24 h]; 15/20 [endotoxin-36 h].)Endotoxin-treated animals in O(2) showed increases in pulmonary superoxide dismutase, catalase, and glutathione peroxidase activities before the usual time of onset of measurable pulmonary edema in untreated animals in O(2). When diethyldithiocarbamate was used to block the superoxide dismutase enzyme rise in the endotoxin-treated rats in O(2), the protective action of endotoxin against pulmonary O(2) toxicity was nullified. In endotoxin-treated, O(2)-exposed mice, there were no lung antioxidant enzyme increases, and no protective effect from O(2) toxicity was achieved. We conclude that, in the rat, a single dose of endotoxin given even 36 h after the onset of hyperoxic exposure results in marked protection against O(2)-induced lung damage; and the increased lung antioxidant enzyme activity in the endotoxin-treated rats appears to be an essential component of this protective action.

Animals↗
PubMed1980

The effect of prenatal dexamethasone treatment on oxygen toxicity in the newborn rat.

To determine whether prenatal corticosteroid therapy had adverse effects on the tolerance of the newborn lung to prolonged high O2 exposure, pregnant rats were given injections of dexamethasone (0.2 mg/kg) at 48 and 24 hours prior to parturition, and the newborn pups were placed in 96% to 98% O2 for the first seven days of life. Dexamethasone treatment resulted in significant decreases in body weight (-17%), lung weight (-30%), lung weight/body weight (-22%), and lung DNA (-18%) compared to untreated rat pups. Despite this growth inhibition, the dexamethasone-treated pups had improved survival in hyperoxia (36/48 = 75% vs 29/48 = 60% for untreated rats, P = .055). In addition, substantial "catch-up" lung growth had occurred by seven days and was complete in 28-day-old rats. Dexamethasone did not interfere with normal pulmonary antioxidant enzyme responses to hyperoxia. Thus, prenatal dexamethasone did not compromise the relative tolerance of the newborn to pulmonary O2 toxicity.

Animals↗
PubMed1979

Protein metabolism in lung: use of isolated perfused lung to study protein degradation.

This study investigates the use of the isolated perfused lung to study protein degradation. Proteins were labeled in vivo for 10 min or for 5 h using L-[U-14C]phenylalanine. When prelabeled lungs were perfused in vitro virtually all of the acid-soluble and acid-insoluble radioactivity in the tissue and perfusate remained as phenylalanine. Protein degradation was measured as the accumulation of free [14C]phenylalanine in ther perfusate; during the time this accumulated the amount of intracellular free phenylalanine and the free phenylalanine space remained constant. Proteins labeled during 10 min had a constant rate of degradation between 45 and 90 min of perfusion (about 11%.h-1); those labeled during 5 h had a constant rate of degradation for 90 (about 3%.h-1). The percent dry lung weight did not change during the perfusion. We conclude that measurable rates of proteolysis of "rapid" and "slowly" turning over proteins can be obtained while the lung is virtually free of edema. This system should allow studies on the modulation of proteolysis in intact lung under defined conditions.

Animals↗
PubMed1979

Degradation of endogenous protein by rabbit pulmonary macrophages.

Pulmonary macrophages were preincubated for 1 or 20 h with L-[U-14C]phenylalanine and the degradation of labeled proteins studied by reincubating these cells in the presence of 4 mM L-phenylalanine and measuring rates of [14C]phenylalanine released from the cells into the medium. We found that proteins prelabeled in 1 or 20 h were degraded 8.0 and 3.0%.h-1, respectively. Decreases in cell viability reduced the rate of protein degradation. Lack of exogenous glucose slowed the rate of degradation of proteins labeled in 1 h, but not of those labeled in 20 h. Varying amino acids in the medium from normal to 5 times normal rabbit plasma levels had no effect on the degradation of either group of proteins. Rates of degradation of both fast and slowly turning over proteins were inhibited during phagocytosis of polystyrene latex particles by about 62 and 33%, respectively. The time course of the changes in protein degradation suggests they are related to intracellular events in the phagocytic process, rather than particle attachment or uptake.

Amino Acids↗
PubMed1979

Protein metabolism in lung. II. Influence of amino acids and glucose on protein degradation.

We used the isolated perfused lung to study protein degradation. Proteins were labeled in vivo during 10 min (fast) or 5 h (slow). The absence of exogenous amino acids lowered the rate of proteolysis of fast but not of slowly turning over proteins. Addition of normal rat plasma levels of amino acids, after 45 min of perfusion without amino acids, returned the rate of proteolysis to control levels. The absence of exogenous glucose increased the rate of degration of rapidly turning over proteins but decreased the degradation rate of slowly turning over proteins. These changes took place in the absence of any measurable effect of amino acids or glucose on the amount of lung water, the rate of perfusate flow, the lung concentration of ATP or the intracellular concentration of free phenylalanine. We conclude that these substrates influence proteolysis in our system and that the degradation of rapidly and slowly turning over proteins are regulated independently in the isolated perfused lung.

Adenosine Triphosphate↗
PubMed1979

Changes in sedimentation of surfactant in ventilated excised rat lungs. Physical alterations in surfactant associated with the development and reversal of atelectasis.

We ventilated excised rat lungs at a constant tidal volume (CTV); they developed areas of atelectasis which could be reversed by a large inflation (CTV + I) or prevented by the addition of positive end-expiratory pressure to the CTV. To explore the possibility that these modes of ventilation led to changes in surfactant, we lavaged the lungs and centrifuged the returns at 500 g; we measured the amount of disaturated phosphatidylcholine (DSPC) in the resultant pellet and supernatant fluid as a marker for surfactant. We found 16.9+/-1.5 (mean+/-SE), 38.0+/-2.4, 18.3+/-1.6, and 21.7+/-2.3% of the total lavage DSPC, in the pellet from freshly excised, CTV, CTV + I, and positive end-expiratory pressure to the CTV lungs, respectively. The total amount of lavage DSPC was the same in all groups. The ultrastructure of acellular material pelleted by sequential centrifugation of lavage returns at 500, 1,000, and 60,000 g was examined. We found mostly tubular myelin in the 500-g and 1,000-g pellets, but no tubular myelin in the 60,000-g pellet. Air inflation pressure-volume measurements from the degassed state revealed that the opening pressure and recoil pressures up to 75% of total lung capacity were significantly higher in the CTV than in the CTV + I lungs. There were no differences between these groups in air deflation or in saline inflation and deflation pressure-volume measurements. Our findings suggest that CTV leads to increases in the tubular myelin form of surfactant and that this leads to increased surface tension in alveoli which results in alveolar collapse.

Animals↗
PubMed1978

Interspecies variation in lung lavage and tissue saturated phosphatidylcholine.

We measured the saturated phosphatidylcholine in lung lavage fluid and in lung tissue after lavage in five vertebrate species. The amount of saturated phosphatidylcholine recovered by lung lavage and from lung tissue showed a direct log linear correlation with species alveolar surface area. The saturated phosphatidylcholine content of lung lavage fluid per square meter of alveolar surface area varied in the sequence: mouse greater than rat greater than rabbit greater than dog greater than cat, and showed a direct correlation with species respiratory rate. We compared the lavage (presumably mainly alveolar) and tissue saturated phosphatidylcholine with the theoretical minimum amount required to produce a monomolecular layer over an area equal to the computed alveolar surface area. The data suggest that there is an alveolar and a tissue reserve of saturated phosphatidylcholine. The size of the alveolar reserve varied in the sequence: mouse greater than rat greater than rabbit greater than dog greater than cat. We conclude that in each species studied there is an alveolar and tissue reserve of saturated phosphatidylcholine and that both reserves are larger in animals with rapid ventilatory rates and small alveoli than in animals with slower breathing rates and larger alveoli.

Animals↗
PubMed1978

2-Deoxy-D-glucose uptake by lung slices from fed and fasted rats.

We studied the uptake and phosphorylation of 2-deoxy-D-[1-14C]glucose (2-[14C]DG) by lung slices from fed and fasted rats to obtain information on the effect of starvation on surgar transport by the lung. We found that 2-[14C]DG is taken up and phosphorylated by the lung, but that, as in other tissues it is not metabolized beyond the phosphorylation step. The accumulation of 2-[14C]DG as free 2-DG does not require energy, fails to show saturation in the range studied (5-100 mM), and is not inhibited by exogenous glucose. The phosphorylation of 2-DG by the lung is energy dependent, saturable, and competitively inhibited by exogenous glucose. Fasting does not interfere with the intracellular accumulation of unphosphorylated 2-DG but causes about a 40% decrease in the accumulation of phosphorylated 2-DG. We conclude that membrane transport does not limit uptake of 2-DG; fasting decreases the phosphorylation of 2-DG.

Animals↗
PubMed1978

Biochemical and anatomical adaptation of the lung to oxygen-induced injury.

A review of anatomical and biochemical responses of the lung to high concentrations of oxygen leads us to postulate a biphasic adaptive response. The early phase entails a defense against life-threatening pulmonary edema engendered by destruction of oxygen susceptible cells forming most of the air-blood interface. This defense is brought about by type II alveolar cell replication to reform a continuous epithelial layer in the alveoli; its success would depend upon the rapidly with which this continuity can be reestablished. Factors favoring a successful defense would include an initial large population of type II cells or the ability of type II cells to divide fast enough to reestablish continuity before of oxygen-sensitive cells (type 1 alveolar epithelial and endothelial cells) proceeds to fatal pulmonary edema; both conditions probably exist in young animals, which are known to be more resistant to hyperoxia than old animals. The second phase of adaptation would require the development of increased tolerance of previously susceptible cells to continued exposure to high oxygen concentrations to prevent their total destruction. We postulate that here the development of new biochemical defenses or the augmentation of those previously present would play a major role.

Animals↗
PubMed1977

Influence of fasting on the lung.

We examined the following in fed rats and in rats fasted for 72 h: 1) the dipalmitoyl lecithin (DPL) content of lung lavage fluid and of the remaining lung tissue, 2) descending air and saline pressure-volume curves of excised lungs, and 3) the volume density of granular pneumocyte lamellar bodies. Lung tissue DPL was decreased by 27% and lavage DPL was decreased by 40% in lungs of fasted rats. The decreased lung DPL content was associated with a 20% decrease in the volume density of lamellar bodies of granular pneumocytes. In spite of the decrease in lavage DPL content, air pressure-volume curves of excised lungs were the same as curves of lungs of fed rats. Saline pressure-volume curves of excised lungs were also the same in fed and fasted rats. The amount of lavage DPL obtained from both fed (1.1 +/- 0.1 mg, n=6) and fasted (0.7 +/- 0.1 mg, n=7) rats exceeded the theoretical minimum amount of DPL (0.5 mg) required for a monomolecular film to cover the alveolar surface of the rat at functional residual capacity. If we assume that lavage DPL represents mainly DPL lining the alveolus (surface film and hypophase) the data suggest that there is an alveolar reserve of DPL above that amount needed to maintain normal alveolar stability.

Animals↗