Changes to the phosphatidylcholine profile, surfactant proteins, and inflammatory markers of bronchoalveolar lavage fluid and plasma in children with acute lung injury are consistent with an alveolar/blood leakage and inflammatory cell membrane degradation products. These changes are due to alveolar capillary membrane damage and cellular infiltration.
Alveolar proteinosis (AP) is an idiopathic condition characterized by excess alveolar surfactant. Although the surfactant proteins (SP) are known to be aberrant, little is known of their variation between patients or their abundance relative to the lipids. We have examined surfactant composition in lavage fluid from 16 normal subjects and 13 patients with AP, one of whom was lavaged on 11 occasions over approximately 13 mo. In this patient we have examined composition on each occasion and in each sequential lavage aliquot. Composition was constant between right and left lung, but it differed markedly between patients. The cholesterol/disaturated phospholipid ratios (CHOL/DSP) were invariably elevated, on average by approximately 7-fold, whereas the SP-A/DSP and SP-B/DSP ratios were generally elevated, in some cases by as much as approximately 40- and approximately 100-fold, respectively. Although AP lavage generally contained more non-thiol-dependent SP-A aggregates and low Mr isoforms, the two-dimensional immunochemical staining patterns varied between patients and right and left lung. In the patient lavaged on multiple occasions, the SP-A/DSP and SP-B/DSP ratios progressively decreased as the patient's condition resolved. Because the SP-B/SP-A ratio was normal in all cases, we suggest that structural changes to the proteins occurred secondarily and that caution must be used in comparing functional data derived using SP-A obtained from patients with AP.
Although acute lung injury (ALI) is associated with inflammation and surfactant dysfunction, the precise sequence of these changes remains poorly described. We used oleic acid to study the pathogenesis of ALI in spontaneously breathing anesthetized rats. We found that lung pathology can occur far more rapidly than previously appreciated. Lung neutrophils were increased approximately threefold within 5 min, and surfactant composition was dramatically altered within 15 min. Alveolar cholesterol increased by approximately 200%, and even though disaturated phospholipids increased by approximately 30% over 4 h, the disaturated phospholipid-to-total phospholipid ratio fell. Although the alveolocapillary barrier was profoundly disrupted after just 15 min, with marked elevations in lung fluid ((99m)Tc-labeled diethylenetriamine pentaacetic acid) and (125)I-labeled albumin flux, the lung rapidly began to regain its sieving properties. Despite the restoration in lung permeability, the animals remained hypoxic even though minute ventilation was increased approximately twofold and static compliance progressively deteriorated. This study highlights that ALI can set in motion a sequence of events continuing the respiratory failure irrespective of the alveolar surfactant pool size and the status of the alveolocapillary barrier.
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.
Swimming rats for up to 2 h in water at 34 +/- 1 degree C increased the rate of breathing by 60% and tidal volume by 200-300%. In each case we infused 20 muCi X kg-1 [methyl-3H]choline chloride, via a caudal vein, 3 h prior to the end of swimming. Maximum specific activity of tissue phospholipid (PL) and alveolar PL (PLalv) occurred in 1 and 12 h, respectively. Total PLalv, specific activity of PLalv and the percentage of total PL released (%A/T) increased within 10 min of start of swimming and were sustained for at least 2 h of swimming [PLalv in mg X g dry lung-1: 5 s swim, 7.3 +/- 0.96 (mean +/- SD; n = 15 rats); 1-h swim, 10.1 +/- 1.1 (n = 23 rats)]. After a 1-h swim, PLalv returned to control within 4 h. Pretreatment with propranolol hydrochloride (10 mg X kg-1) (P), atropine methyl nitrate (3 mg X kg-1) (A), indomethacin (15 mg X kg-1), and cyproheptadine (1 mg X kg-1) did not alter the increase in PLalv with swimming, however, both P and A reduced the increase in specific activity of PLalv and %A/T. We suggest that the exercise releases surfactant from two pools: a readily released pool that responds to direct distortion of the alveolar type II cell and a pool that is under sympathetic nervous control.
We used the isolated rat lung to investigate surfactant release. The lung was ventilated at 60.min-1 with 5% CO2-95% O2 and perfused at 10 ml.min-1 with Krebs-bicarbonate (4.5% albumin). After 20 min during which antagonist drugs were present, the lungs were either hyperventilated or agonist drugs were added. After another 15 min lungs were lavaged. Peak inspired pressures (PIP) in excess of 12 cmH2O produced progressively greater phospholipid (PL) yields. Whereas ventilating with PIP of 9 cmH2O and end-expired pressure(EEP) of 5 cmH2O produced 5.9 +/- 0.8 (mean +/-SD) (n = 17) mg PL. g dry lung-1, ventilating with PIP of 20 cmH2O and EEP of 0 cmH2O produced 10.1 +/- 1.3 (n = 26). PL release was unaffected by tetrodotoxin, propranolol, atropine, cyproheptadine, or indomethacin. PL was increased by salbutamol and dibutyryl adenosine 3',5'-cyclic monophosphate but not by pilocarpine or dibutyryl guanosine 3',5'-cyclic monophosphate. We conclude, that increasing tidal volume immediately releases surfactant, probably by distorting the type II cell and elevating cAMP. An intrapulmonary neural reflex is not involved in this response of the isolated rat lung, nor is histamine, 5-hydroxytryptamine, or a prostaglandin.
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