Biomedical subjects

T E Nicholas

Publications and source records attributed to T E Nicholas.

At least 37 records · Page 2Linked to original sources

PubMed1996

Differential changes in SP-A and disaturated phospholipids in the isolated perfused rat lung and in vivo.

Alveolar disaturated phospholipids (DSPA) increase in vivo in rats with hyperpnea and in isolated perfused lungs (IPL) in response to either salbutamol or increasing tidal volume (VT). Because surfactant protein-A (SP-A) may play a role in surfactant homeostasis, we have examined the relationship between SP-A and DSP in the alveolus lamellar bodies (LB-A), and in a vesicular (LB-B) lung subfraction. Whereas 2 h swimming increased total DSPA (approximately 48%), it had no effect on alveolar SP-A (SP-AA). In the IPL, salbutamol increased total DSPA (approximately 30%) and SP-AA (approximately 41%); increasing VT (2.5-fold) only increased DSPA (approximately 22%). SP-A and DSP also varied differentially in the tubular myelin-rich and -poor subfractions. In both the IPL and in vivo, we found inverse relationships between DSPA and SP-AA/DSPA, indicating that although SP-AA and DSPA are related, they vary independently. Whereas total SP-AA/DSPA varied between 0.046 and 0.074, it remained constant in LB-A (approximately 0.015) and LB-B (approximately 0.010), suggesting that DSP and SP-A are secreted differentially and that only a small portion of SP-AA is derived from lamellar bodies.

Animals↗

PubMed1995

Serum surfactant protein-A levels in patients with acute cardiogenic pulmonary edema and adult respiratory distress syndrome.

Detection of alveolo-capillary damage has important implications for treatment modalities in ventilated patients. Although surfactant protein-A (SP-A) is normally only found in appreciable amounts in the lung, we describe significantly elevated concentrations in the sera of patients with acute cardiogenic pulmonary edema (median, 250 ng/ml; range, 180 to 364; n = 10) and in those with the adult respiratory distress syndrome (ARDS) (median, 378 ng/ml; range, 215 to 1,378; n = 15) relative to healthy control subjects (median, 175 ng/ml; range, 123 to 248; n = 15) and ventilated patients with no cardiorespiratory disease (median, 169 ng/ml; range, 126 to 253; n = 6) (p < 0.01, in all cases). Serum SP-A was inversely related to blood oxygenation and to static respiratory system compliance both at the time of the patient's entry into the study (p < 0.005, rs = -0.51, n = 31; p < 0.001, rs = 0.82, n = 17; respectively) and during the course of admission (p < 0.001, rs = -0.34, n = 168; p < 0.001, rs = -0.50, n = 111; respectively). In addition, we describe in detail three cases of ARDS where lung function either improved, remained static, or deteriorated. We conclude that serum SP-A is an acute indicator of lung function and alveolo-capillary membrane injury.

Adult↗

PubMed1994

Pulmonary-type surfactants in the lungs of terrestrial and aquatic amphibians.

We examined the composition and function of pulmonary surfactants in amphibians inhabiting aquatic and terrestrial habitats with particular regard to the influences of (1) variations in body temperature, (2) external hydrostatic pressure and (3) breathing pattern. Two fully aquatic salamanders, and the completely terrestrial cane toad Bufo marinus (all maintained at 21-23 degrees C) were selected. Whereas one of the salamanders (Siren intermedia) possessed gills and lungs, Amphiuma tridactylum only possessed lungs. We determined the amounts of cholesterol (Chol), disaturated phospholipids (DSP) and total phospholipid (PL) in lavage of all three species, and also determined the types of phospholipids of B. marinus and A. tridactylum. DSP lowers surface tension at the air-water interface in the lung, while Chol and unsaturated phospholipids assist spreading and maintain the DSP in its disordered, liquid-crystalline state at high lung volumes. All three species had significant amounts of pulmonary-type surfactant. The two aquatic salamanders had identical ratios of both Chol/PL and DSP/PL both of which in turn were nearly twice those of B. marinus. All three species had similar Chol/DSP ratios. Aquatic salamanders sustain high external hydrostatic pressures exerted by the aquatic environment and tend to collapse their lungs during expiration. We hypothesize that these salamanders might require a DSP-rich surfactant to prevent the epithelial surfaces from adhering and large amounts of Chol to keep the DSP fluid. The terrestrial B. marinus has less DSP, suggesting a surfactant which is fluid over a large range of temperatures. Possibly, cane toads do not require a DSP rich surfactant as they neither collapse their lungs on deflation, nor experience external hydrostatic pressures promoting lung collapse. The PL profile of B. marinus lavage was similar to that of other frogs and mammals, containing phosphatidylcholine (PC) as the predominant phospholipid together with substantial amounts of phosphatidylglycerol (PG). On the other hand, although A. tridactylum exhibited high levels of PC, it contained phosphatidylinositol (PI) in place of PG, a pattern typical of reptiles and birds.

Amphibians↗

PubMed1994

Composition of human pulmonary surfactant varies with exercise and level of fitness.

We have tested the hypothesis that the composition of alveolar surfactant varies with pattern of breathing and level of fitness. We examined three major components of surfactant, surfactant protein A (SP-A), disaturated phospholipids (DSP), and cholesterol (CHOL) in bronchoalveolar lavage (BAL) fluid from 12 healthy men before and after exercise. Fitness was assessed as work load/heart rate ([kpm.min-1]/[HR.HRmax-1]) achieved during cycling for 30 min at 90% theoretical maximal heart rate. Using a bronchoscope, four 20-ml vols of 0.15 M NaCl at 37 degrees C were instilled and then recovered from first a right upper and then a right lower lobe segmental bronchus. As we found no differences in the BAL from upper and lower lobes, the fluid was combined. We found a direct relationship between CHOL and DSP (rs = 0.84, p < 0.001), SP-A and CHOL (rs = 0.40, p < 0.025), and between SP-A and DSP (rs = 0.44, p < 0.025). The change in the ratios CHOL/DSP, SP-A/CHOL, and SP-A/DSP immediately after exercise was correlated with fitness (rs = -0.56, p < 0.025; rs = 0.75, p < 0.005; rs = 0.62, p < 0.025, respectively). We conclude that the composition of surfactant can change rapidly with exercise in a manner related to fitness, and we suggest that this is consistent with the existence of at least two pools of tissue surfactant of different composition supplying the alveolar compartment.

Adult↗

PubMed1994

Distribution of surfactant protein A in rat lung.

Although surfactant protein A (SP-A) is an integral component of alveolar surfactant, its relative abundance in lamellar bodies, regarded as the intracellular storage organelles for surfactant, remains contentious. We have previously shown that lamellar bodies, isolated from rat lung by upward flotation on a sucrose gradient, can be subfractionated into classic-appearing lamellar bodies (Lb-A) and a vesicular fraction (Lb-B), which we have speculated may be a second release form of surfactant. In the present study, we have used two-dimensional protein electrophoresis and immunochemical analysis to clarify the origin and the composition of these two subcellular fractions. In addition, we have examined the hypothesis that the secretion of SP-A and surfactant phospholipids occurs by independent pathways by examining the distribution of SP-A, total protein, and disaturated phospholipids (DSP) in the tubular myelin-rich (Alv-1) and tubular myelin-poor (Alv-2) fractions separated from lavaged material and in Lb-A and Lb-B isolated from both lung homogenate and purified alveolar type II cells. Our findings indicate that Lb-B is derived from type II cells, although they do not indicate whether it is a secretory form of surfactant, a reuptake vesicle, or a mixture of both. We found that the lung has a large tissue pool of immunoreactive SP-A. The %SP-A/DSP of total lamellar bodies isolated from type II cells was 0.96 +/- 0.1 (mean +/- SE), intermediate between that in Lb-A (1.67 +/- 0.13) and in Lb-B (0.65 +/- 0.04). In contrast, the %SP-A/DSP was 11.16 +/- 0.84 in whole lung homogenate and 13.14 +/- 1.71 in whole type II cells. In the alveolar compartment, the %SP-A/DSP was 17.38 +/- 3.40 in Alv-1, 6.34 +/- 0.31 in Alv-2, and 10.49 +/- 1.43 in macrophages, values an order of magnitude greater than found with the lamellar bodies. Our results indicate that only a relatively small portion of alveolar SP-A is derived from lamellar bodies, and we suggest that secretion of SP-A and DSP occurs via independent pathways.

Animals↗

PubMed1993

Turnover of cholesterol and dipalmitoyl phosphatidylcholine in surfactant of adult rat lung.

In order to compare the turnover of two major surfactant components, [1 alpha,2 alpha (n)-3H]cholesterol and [methyl14C choline] dipalmitoyl phosphatidylcholine (DPPC) were introduced as lamellar bodies via the trachea into lightly anesthetized rats which were then allowed to recover. The radiotracers were assumed to have entered the alveolar surfactant pool and to have subsequently recycled in part into the lamellar bodies of alveolar type II cells. For DPPC, the specific activity vs. time curves of tubular myelin rich (alv-1) and tubular myelin poor (alv-2) alveolar lavage fractions were similar, and there was a plausible precursor-product relationship between lamellar bodies and either (or both) of these compartments. In contrast, however, the specific activities of alv-1 and alv-2 for cholesterol were quite different, allowing us to reject the hypothesis of a precursor-product relationship between classical lamellar bodies and alv-2. The estimated turnover time for DPPC in alv-1 was 240 or 206 min, depending on which subfraction of lamellar bodies one takes to be the precursor. For cholesterol it was 583 or 624 min. These longer turnover times for cholesterol should lead to a greater than twofold increase in the relative concentration of cholesterol in the putative product compartment. Such an increase was not found. We interpret this as reflecting either noncompartmental behavior of the alveolar surfactant pool, or multiple pools of lamellar bodies with different turnover times.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1993

The role of surfactant in the static lung mechanics of the lizard Ctenophorus nuchalis.

We previously showed that the lung of the central Australian lizard, Ctenophorus nuchalis, contains a large amount of surfactant, the composition of which varies with body temperature. We now show that the specific compliance of the lungs of these lizards remains constant regardless of whether they were maintained at 10, 18, 27, 37 or 43 degrees C for 4 hours. In contrast, the opening pressure was constant up to 27 degrees C, but decreased at 37 and 43 degrees C. When we lavaged the lungs in situ to remove the majority of surfactant, specific compliance decreased while opening pressure increased. The lungs of C. nuchalis are essentially two bubbles, with the left one larger at low and intermediate volumes. After collapsing both lungs, the larger left lung always inflated first. However, following lavage the smaller right lung inflated first. As the larger lung, when collapsed, would have a much greater area of epithelial contact, this result is consistent with surfactant acting as an 'antiglue'. During deflation the smaller lung collapsed first, consistent with the law of Laplace. Compliance did not change in the saline-filled lung suggesting that the gas-liquid interface does not play a major role. We conclude that in the lungs of these lizards, surfactant is acting as an antiglue. This might be important during periods of apnea at low body temperatures, when residual volume is small and epithelial surfaces may come into contact.

Animals↗

PubMed1993

Characterization and immunohistochemical localization of the 15 kD protein isolated from rat lung lamellar bodies.

We have characterized a protein of approximately 15 kD (lb15) derived from rat lung lamellar bodies, and then sequenced the first 42 residues. Following the normal isopycnic sucrose gradient ultracentrifugation, we diluted the band containing the crude lamellar body fraction with an equal volume of cold distilled water and further centrifuged it at 2,000 x g for 30 min to pellet a fraction of lamellar bodies. Under the electron microscope, this fraction appeared intact and highly purified. When this fraction was subjected to polyacrylamide gel electrophoresis, the major protein was one of 15 kD, regardless of whether the fraction was extracted or unextracted, reduced or unreduced; only a small amount of 35 kD protein was detected with Coomassie Blue staining. Disruption of lamellar bodies revealed that the limiting membrane was particularly enriched with lb15. Immunohistochemistry indicated that lb15 was present in lamellar bodies and tubular myelin, suggesting it was secreted along with the lipid. Amino acid analysis revealed a protein with 13.5% basic and 10.6% acidic residues. The N-terminal appeared particularly highly charged, with 32% of the charged residues in the first 14 amino acids. The lb15 protein is identical to rat lysozyme for the first 23 residues, with the important exception of residue 6, which is histidine in lb15 and cysteine in lysozyme. Residue 24 was not identified. Lb15 was also present in lavage material. We conclude that lb15 is the major protein in rat lung lamellar bodies, has a highly charged N-terminal, and shares some sequence homology with rat lysozyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1992

Effect of artificial ventilation and anaesthesia on surfactant turnover in rats.

We have tested the hypothesis that breathing releases pulmonary surfactant via distortion of the alveolar type II cell. Gas exchange was maintained in the anaesthetized rat by applying high frequency (10 Hz) oscillations (HFO) to the chest wall; this resulted in apnoea within two to three breaths. After instrumentation under anaesthesia for 30 min, rats were infused with [3H]choline and [14C]choline, and we compared the tubular myelin-rich (PLalv-1) and -poor (PLalv-2) alveolar phospholipids and the microsomal and lamellar body phospholipids (PLlb) together with their specific activities after three forms of ventilation for 90 min: HFO (group 1), conventional mechanical ventilation (group 2) and spontaneous breathing (group 3). Group 4 was killed after surgical instrumentation and in group 5 the lungs were removed immediately after induction of anaesthesia. Groups 1-3 did not differ in any measured variable. Groups 1-4, which were anaesthetized for 30-120 min, had a lower PLalv-2 than did group 5. In contrast, PLlb was greater in groups 1-3, which were anaesthetized for 120 min, than in groups 4 and 5. In conclusion, we have successfully maintained normal gas exchange during complete apnoea by applying external HFO in rats for periods up to 90 min. Compared to mechanically ventilated or spontaneously breathing anaesthetized rats, surfactant turnover was unaltered by HFO, despite a markedly reduced tidal volume. However, the barbiturate anaesthetic itself appeared to inhibit surfactant turnover. We suggest that distortion of the type II cell may be the stimulus for surfactant release at tidal volumes above resting values.

Anesthesia↗

PubMed1990

Uptake of instilled radiolabeled lamellar bodies from alveolar compartment of the rat.

Following the instillation of lamellar bodies containing dipalmitoyl phosphatidyl-[3H]choline (DPPC) down the trachea of adult rats, we found that the half-life of alveolar [3H]-DPPC was 85 min and the time constant was 120 min. As much as 85% was recycled. When we labeled the DPPC with both [3H]choline and [14C]acetate, the ratio 3H/14C increased in the alveolar compartment and then increased further in the lamellar body fraction of the recipient lungs, suggesting that some deacylation-reacylation was occurring. Further evidence of degradation was an increase in free [3H]choline in the microsomal fraction. Whereas hyperpnea induced by breathing 5% CO2-13% O2-82% N2 increased the reuptake of DPPC, reuptake did not appear to be enhanced in the rest period immediately after hyperpnea induced by swimming, when alveolar DPPC was still markedly elevated. Propranolol did not affect reuptake, suggesting that beta-adrenoreceptors were not essential. We suggest that reuptake is coupled more to release than to the amount of surfactant in the alveolar compartment.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1990

Effect of pattern of breathing on subfractions of surfactant in tissue and alveolar compartments of the adult rat lung.

We have used tow previously characterized models of hyperpnea in vivo and different modes of ventilation in the isolated perfused rat lung to investigate changes in the phospholipid content of tubular myelin-rich (PLalv-1) and -poor (PLalv-2) fractions isolated from lavaged material and of two lamellar body subfractions. A vesicular lamellar body subfraction (lbB) was preferentially released during 30-min swimming. However, during the subsequent 3-h recovery period there was a preferential supplementation of the classic-appearing lamellar body fraction (lbA). Hyperpnea induced by exposure to 5% CO2/13% O2/82% N2 led to an increase in lbA after 12 h and in lbB after 48 h. Whereas PLalv-2 was elevated above control values after 8 h, PLalv-1 remained unchanged until 24 h. In the perfused lung isolated from rats infused with [methyl-3H]choline chloride 3 h previously, salbutamol, a deep breath, and increased tidal volume (VT) all increased total alveolar phospholipids; however, the pattern of change was very different. Salbutamol markedly elevated PLalv-1 and increased the specific activity of both alveolar fractions. In contrast, a single deep breath increased PLalv-2 while slightly increasing the specific activity of PLalv-1. Finally, an increased VT decreased PLalv-1 while inducing a large increase in PLalv-2; it increased specific activity in both alveolar fractions. Both salbutamol and an increased VT decreased phospholipids in lbA. We conclude that lbA and lbB vary in their response to different stimuli. In vivo, PLalv-1, the tubular myelin-rich fraction, remains very constant, a fact consistent with its being the controlled variable in surfactant homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗

PubMed1989

Effect of hyperpnea on enzymes of the CDPcholine path for phosphatidylcholine synthesis in rat lung.

We have examined the activity of three enzymes in pulmonary surfactant phosphatidylcholine synthesis following the hyperpnea induced by having rats either inspire 5%CO2/13%O2/82%N2 for 24 hr or swim in thermoneutral water for 30 min. Both stimuli markedly increase frequency and tidal volume of breathing and promote the release of surfactant. Lungs were perfused to remove blood, lavaged, and then homogenized in 1 mM Hepes, 0.15M KCl at pH 7.0. The homogenate was centrifuged at 9,000 g (av) for 10 min to sediment the mitochondria and lamellar bodies and at 100,000 g (av) for 60 min to obtain the microsomal and cytosol fractions. Incubations were carried out under determined optimal conditions and zero order kinetics. Choline kinase (CK), cholinephosphate cytidylyltransferase (CP-cyT) and choline phosphotransferase (CPT) were assayed by the incorporation of [methyl-14C]choline chloride into phosphocholine, [methyl-14C]phosphocholine into CDPcholine, and [14C]CDPcholine into phosphatidylcholine, respectively. The incubation products were separated by thin-layer chromatography. Whereas both forms of hyperpnea increased the activity of CP-cyT in the microsomal fraction, they had no effect on the activity of either cytosolic CP-cyT and CK, or microsomal CPT. A similar increase in tidal volume in an isolated perfused rat lung had no effect. We conclude that, in vivo, hyperpnea increases the activity of CP-cyT, the rate-limiting enzyme in phosphatidylcholine synthesis. Whether this is due to an increase in the amount of enzyme, or of a cofactor, is unknown.

Animals↗

PubMed1989

The processing of exogenous cholesterol in the alveolar compartment of the rat lung.

We have examined the esterification of [3H]cholesterol following the intratracheal instillation of a tracer amount into the isolated rat lung perfused with Krebs bicarbonate containing 4.5% albumin. At 5, 30 and 60 min after instillation, lungs were lavaged at 2 degrees C with 3 x 10 ml of 0.15 M NaCl, each volume instilled and withdrawn three times. Each lung was lavaged at only one time point. The saline recovered was centrifuged at 150 g (5 min) to sediment the macrophage-rich fraction, leaving the surfactant in the supernatant. The amounts and specific activity of cholesterol and cholesteryl ester were measured following isolation by high performance liquid chromatography of the free cholesterol and the hydrolyzed ester-derived cholesterol. There was a rapid fall in [3H]cholesterol in the surfactant fraction, accompanied by a reciprocal increase in [3H]cholesteryl ester in the macrophage-rich fraction, while the level of free [3H]cholesterol in that fraction remained very low. These data are consistent with exogenous cholesterol being rapidly esterified in the alveolus, and the ester then being cleared by the macrophages. We were unable to locate the actual site of esterification.

Animals↗

PubMed1989

A comparison of the surfactant associated lipids derived from reptilian and mammalian lungs.

The lungs of the central netted dragon Ctenophorus nuchalis are bag-like, with most of the gas exchange region located in the anterior third. Although the faveoli are much larger than the mammalian alveoli, the lizard at 37 degrees C has approximately 70 times more surfactant phospholipid per unit area of respiratory surface than does a similar sized mammal. However, when expressed as per wet lung weight, lizards and rats possessed similar amounts of phospholipids. Dipalmitoylphosphatidylcholine was the principal phospholipid in both species. However, major differences existed in the phospholipid, neutral lipid and fatty acid profiles. Whereas the lizard contained neither phosphatidylglycerol nor phosphatidylethanolamine it had more cholesterol, esterified cholesterol, acylglycerides and unsaturated fatty acids. Although the ratio of saturated:unsaturated fatty acids was similar in rats and lizards, palmitic acid predominated in the former. The composition of lizard surfactant suggests that it would adsorb rapidly at reduced body temperature.

Animals↗

PubMed1988

Control of alveolar surfactant in rats at rest and during prolonged hyperpnoea: pharmacological evidence for two tissue pools of surfactant.

1. Propranolol, atropine and indomethacin (i.p.) affect neither the amount (PLalv), nor the specific activity (PLalvsp.act.) of alveolar surfactant-type phospholipids lavaged from the lungs of unanaesthetized rats, either at rest or made hyperpnoeic for 24 h with 5%CO2/13%O2/82%N2. 2. Whereas salbutamol (280 micrograms kg-1 body weight, i.p.) consistently increased PLalv and PLalvsp.act., pilocarpine (1.5, 3, 10 and 50 mg kg-1, i.p.) and labetalol (1 and 5 mg kg-1, i.p.) had no effect. The dose of pilocarpine reported by others to release surfactant (150 mg kg-1) induced marked salivation, diarrhoea, chromodacryorrhoea and a three-fold increase in tidal volume. 3. In the isolated perfused lung of the rat, salbutamol (1.5 microM) consistently increased PLalvsp.act, whereas pilocarpine (0.1 and 1 microM) had no effect on these variables. 4. In the isolated perfused lung, the maximum amount of surfactant that could be released by salbutamol (0.5 mM) was smaller than that which could be released in response to an increase in tidal volume (peak inflation pressure 28 cmH2O). 5. When the concentration of salbutamol in the isolated perfused lung was adjusted to produce the same increase in PLalv as did a single simulated deep breath, the PLalvsp.act was significantly increased by salbutamol, but not by the simulated deep breath. 6. We conclude, that neither the autonomic nervous system nor the prostaglandin system is essential for the release of surfactant at rest or during hyperpnoea. Furthermore, we suggest that two pools of surfactant, with different release mechanisms, exist in lung tissue.

Albuterol↗

PubMed1988

Surfactant-associated 15- and 35-kDa proteins are concentrated in different organelles in rat lung tissue.

We have used isopycnic gradient ultracentrifugation to isolate a total lamellar body fraction (total-lb) from rat lung and then further subfractionated this using differential centrifugation to obtain two distinct subpopulations of organelles. When the total-lb was diluted to 0.25 M with sucrose and centrifuged at 8000 X for 30 min we obtained a fraction (lbA) that contained primarily intact classic-appearing lb. When the supernatant was then centrifuged at 80,000 X g for 60 min we obtained a vesicular fraction (lbB). Whereas both fractions had an identical phospholipid composition, their enzyme profiles differed markedly. The lbA had a higher level of beta-glycerophosphatase, while lbB had more 5'-nucleotidase. Moreover, lbB had a phospholipid:protein ratio of 9.2 while lbA had one of 6.3. An examination of the specific activity-time curves revealed that lbA had a curve that was broader and reached a peak earlier than lbB, but the downslopes of both curves were identical; they did not bear a classic precursor-product relationship to one another. The two fractions differed very significantly in their protein profiles. Whereas lbA contained a large amount of a 15-kDa protein with very small amounts of 35-, 37-, 38-, 45-, and 60-kDa proteins, lbB contained predominantly a 35-kDa protein with smaller amounts of 15-, 23-, 26-, 37-, 38-, 45-, and 60-kDa proteins. We suggest that lbB is surfactant taken back up into the alveolar type II cell, or a second release form of tissue surfactant, or a mixture of the two.

Animals↗

PubMed1987

Identification of precursor-product relationships in kinetic studies involving radiolabeled tracer molecules.

In radiotracer studies, the estimation of turnover time usually depends on the assumption of steady-state compartmental precursor-product (SCP) behaviour in the pools being studied. Deviation from SCP behaviour is currently measured from the extent of hysteresis, R, in an 'area plot': a plot of the time-integrated difference between precursor and product specific activities (spec. act.) against product spec. act. We propose two approaches to evaluating the statistical significance of apparent deviations from SCP behaviour in experimental data. The first constructs the sampling distribution of R. The second compares the variance in replicate data with the value of the objective function minimized in the least squares estimation of product turnover time. We show that this test closely approximates a variance ratio (F) test. Applied to [methyl-3H]choline and [14C]acetate tracer data from lung phospholipid pools in eupneic and hyperpneic rats, the analysis rejects SCP relationships between lamellar bodies and two subfractions of alveolar lavage material.

Analysis of Variance↗

PubMed1987

Changes in surfactant pools after a physiological increase in alveolar surfactant.

We have used previously characterized models to investigate the reuptake of surfactant from the alveolus. In model 1, rats were swum in a water bath at 33 degrees C for 30 min, which increased tidal volume (VT) approximately 300% and frequency 60%; they were then allowed to rest for up to 4 h. In model 2, rats were exposed to 5% CO2-13% O2-82% N2 for 24 h, which increased both VT and frequency approximately 200%; these rats were then rested for up to 24 h. In both models we harvested a tissue fraction (lamellar bodies, lb) and two alveolar fractions--tubular myelin rich (alv-1) and tubular myelin poor (alv-2). Immediately after swimming, lb-dipalmitoylphosphatidylcholine (DPPClb) was 18% below the control of 0.94 +/- 0.037 (SE) mg/g wet lung (n = 24 rats; P less than 0.05); this returned to control by 2 h. Whereas DPPCalv-1 was constant at all time points, DPPCalv-2 was increased 50% above the control of 2.68 +/- 0.085 mg/g dry lung (n = 27 rats; P less than 0.001) immediately and up to 1 h after swimming. It returned to control levels between 2 and 3 h. After gas exposure, DPPC in lb, alv-1, and alv-2 was 33, 64, and 89%, respectively, above controls. All three fractions had normalized after 24 h. Our results demonstrate marked differences in the response of the surfactant system to acute and more prolonged stimuli. Of particular interest was the constancy of alv-1 with swimming, suggesting that it may be the controlled variable. However, the system appeared to be reset by prolonged hyperpnea, a process that may involve an increase in synthesis of surfactant.

1,2-Dipalmitoylphosphatidylcholine↗