Rates of replacement of lecithins and alveolar instability in rat lungs

Df, Tierney; Clements, J. A.; Trahan, HJ

doi:10.1152/ajplegacy.1967.213.3.671

Cited by 132 publications

(48 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If phosphatidylcholine is being degraded and its components resynthesized into new phosphatidylcholine, the apparent half-life will be considerably longer than the actual half-life of an individual phosphatidylcholine molecule. Our findings are clearly different from the half-life values obtained by using intravenously injected surfactant precursors in adult rats and rabbits (10,11,19,20). These differences are presumably due to a different mode of administration of isotope, different levels of maturity, and species differences.…”

Section: Discussioncontrasting

confidence: 99%

“…The estimated half-life values vary, depending on type of labeled phospholipid precursor used, type of animal studied, and the maturity of the animals. An approximate tlI2 of 16 h has been reported for lung phosphatidylcholine (PC) in adult rats and rabbits, using radiolabeled palmitic acid as a precursor (10,11,19,20). Again using labeled palmitic acid, the biologic ttI2 for alveolar surfactant was estimated to be 54 and 45 h in newborn and adult sheep, respectively (8).…”

Section: Speculationmentioning

confidence: 99%

See 1 more Smart Citation

Metabolism of Exogenously Administered Natural Surfactant in the Newborn Lamb

1982

View full text Add to dashboard Cite

Summawre~orted t1 12 may be in error due to continued secretion of isoto~e[3H]-Palmitate labeled natural lamb surfactant and free [14C]-choline were mixed with the lung fluid of 11 term lambs at cesarean section, before the first breath. After receiving the isotope, the lambs were delivered, allowed to breathe spontaneously, and were subsequently sacrificed from 5 min to % h of age. Alveolar washes, lung homogenates, microsomal and lamellar body fractions of lungs, and pulmonary alveolar macrophages were examined for the presence of labeled phosphatidylcholine. Analysis of the labeled natural surfactant kinetic data revealed an apparent tlIz of phosphatidvlcholine in the whole lung of 6.0 davs. This half-life can be interpreted only as a rough estimate." Appearance of considerable I3H] labeled phosphatidylcholine in the lung homogenates demonstrated uptake of phosphatidylcholine from alveoli into lung tissue. The surfactant-associated label in homogenates was localized preferentially to lamellar body fractions. Some of the administered ['4CI-choline appeared in phosphatidylcholine. Almost all of this labeled phosphatidylcholine was associated with the homogenate. Extremely small % of administered I3HI and Ir4C] were found in pulmonary alveolar macrophages. SpeculationThe prolonged tl/z measured in this study indicates very slow turnover of alveolar phosphatidylcholine and/or considerable reutilization of label and possibly of the entire phosphatidylcholine molecule. The concentration of label in lamellar bodies raises the possibility that alveolar phosphatidylcholine may be degraded and its components utilized for synthesis of new phosphatidylcholine or that alveolar phosphatidylcholine may be absorbed into type-2 alveolar cells and resecreted intact. The finding of [l4Cl labeled phosphatidylcholine in lung homogenate but not in alveolar wash indicates that, even if choline were released by intra-alveolar degradation of surfactant, it is not used to a significant degree for synthesis of new surfactant phosphatidylcholine.The ultimate fate of surfactant phospholipids, once secreted into the alveoli, remains to be defined. Reasonable speculations include: (1) removal via the lymphatic or circulatory systems, (2) metabolism by alveolar macrophages, (3) surface spreading into the airways, or (4) reuptake into pulmonary parenchymal cells with reutilization of all or part of the phospholipid molecule. Estimates of the biologic half-life (tl/z) of surfactant phospholipids in lung parenchyma and in the alveoli have been derived by utilizing radiolabeled phospholipid precursors. The estimated half-life values vary, depending on type of labeled phospholipid precursor used, type of animal studied, and the maturity of the animals. An approximate tlI2 of 16 h has been reported for lung phosphatidylcholine (PC) in adult rats and rabbits, using radiolabeled palmitic acid as a precursor (10,11,19,20). Again using labeled palmitic acid, the biologic ttI2 for alveolar surfactant was estimated to be 54 and 45 h in newborn and adul...

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Speculationmentioning

confidence: 99%

Metabolism of Exogenously Administered Natural Surfactant in the Newborn Lamb

1982

View full text Add to dashboard Cite

show abstract

“…The appearance and half-life of labeled lecithin in lung parenchyma has been used as a measure of overall metabolism of lung lecithin (3,10,11,21,(27)(28)(29). Two different radioactive precursors of lecithin were used here to study lecithin metabolism; each precursor enters the lecithin molecule by different pathways.…”

Section: Discussionmentioning

confidence: 99%

“…These measurements have been made in the adult rat using several different radioactive lecithin precursors to pulse label lecithin (3,10,11,21,(27)(28)(29) and in adult mice using autoradiographic techniques (8). Recently we reported the time of appearance of pulse labeled lecithin in the alveolar space and the biological half-life values for alveolar and lung lecithin in adult rabbits (1 8).…”

Section: Speculationmentioning

confidence: 99%

Lecithin Appearance and Apparent Biologic Half-Life in Term Newborn Rabbit Lung

1978

View full text Add to dashboard Cite

SummaryThe lung lecithin of term newborn rabbits was labeled by injecting the lecithin precursors palmitic acid and cholme into the pregnant doe shortly before delivery of the newborn rabbits by cesarean section. The newborn lungs were lavaged to yield an alveolar wash lecithin sample and the tissue was homogenized and fractionated into lamellar body and microsomal fractions by differential and density gradient centrifugation. Lecithin was isolated from the lung parenchyma, microsomes, lamellar bodies, and alveolar wash by two-dimensional thin layer chromatography, and the specific activity of the lecithin in each fraction was determined. Comes are presented showing the time of appearance of the radioactive lecithin in each lecithin fraction. The apparent biological half-life of lecithin in each fraction was measured.The specific activity of lecithin was high in microsomal fractions soon after palmitic acid or choline administration. The lamellar body fraction was free of radioactive lecithin for 3 hr, and maximal specific activity of lamellar body lecithin was reached only after 20 hr. The appearance of radioactive alveolar lecithin followed a curve very similar to that of the lecithin in the lamellar body fraction.The apparent half-life of lung parenchymal lecithin from newborn lung labeled with palmitic acid was 57 hr, whereas the apparent half-life of alveolar lecithin was 136 hr. The lecithin in lung and alveolar wash labeled with choline had a longer halflife than did lecithin labeled with palmitic acid. Measurements of lecithin appearance and apparent half-life are compared to similar measurements in adult rabbits. SpeculationThe striking characteristics of newborn lung lecithin are the 3-hr lag before the appearance in the alveolus of de novo synthesized lecithin, the prolonged time (20 hr) before maximal specific activity of alveolar lecithin is achieved, and the very long! apparent half-life of alveolar lecithin. If these measurements are applicable to other term and premature mammals, they must rely entirely on lecithin stored in anticipation of birth to maintain alveolar stability at birth. The long lag before significant lecithin synthesized de novo can reach the alveolar space precludes synthesis contributing to alveolar stability until many hours after birth. The recovery from the respiratory distress syndrome may not depend on maturation of the ability to synthesize lecithin; rather, the prolonged recovery phase may reflect the long times required for appreciable quantities of de novo synthesized lecithin to reach the alveolar space. However, once alveolar stability is achieved, short interruptions of lecithin synthesis, by reversible acidosis, for example, should not cause respiratory distress mediated by lecithin deficiency.The times required for lecithin synthesis and appearance in the alveolar space and the biological half-life of alveolar surfactant lecithin are measurements essential to an understanding of surfactant physiology. These measurements have been made in the adult rat using sever...

show abstract

“…Since the quality of phospholipids in a small volume in vivo lavage is similar to that in quantitative ex vivo lung lavage (16), it may be possible to evaluate the pool size and the turnover of surfactant by means of a surfactant size and the turnover of surfactant by means of a surfactant marker introduced to the airways. The turnover of surfactant has been extensively studied in animals using phospholipid and protein precursors (I 2-14, [17][18][19][20]. Rodents tend to have a shorter biological half-life of phosphatidylcholine than lambs ( 18, 2 1, 22).…”

mentioning

confidence: 99%

Effect of Surfactant Substitution on Lung Effluent Phospholipids in Respiratory Distress Syndrome: Evaluation of Surfactant Phospholipid Turnover, Pool Size, and the Relationship to Severity of Respiratory Failure

et al. 1986

View full text Add to dashboard Cite

ABSTRACT. The turnover and pool size of surfactant has Abbreviations been studied in animals, but there is little similar information in humans. In the present investigation lung effluent phospholipids were studied in 29 small preterm infants with severe RDS. Thirteen were treated with mechanical ventilation, and 16 additionally received natural human surfactant. The first dose (60 mg surfactantlkg body wt) was given between 2 and 10 h of age, and the surfactant was given again if there was an insufficient response. Together 260 aspirates, recovered during routine suctioning of the airways, were analyzed for phospholipids. Phosphatidylglycerol, present only in exogenous surfactant, was used as a specific marker to estimate the apparent pool size and the half-life of surfactant phospholipid. In addi-.tion, the saturated phosphatidylcholine/sphingomyelin ratios were correlated with the ventilatorv index (mean airway pressure X fractional inspiratory oxygen/arterial oxygen tension). There was a linear correlation between the ventilatory index and the saturated phosphatidylcholine/ sphingomyelin ( r --0.70) but no consistent correlation between the ventilatory index and the amount of phospholipids in the aspirate. The saturated phosphatidylcholine/ sphingomyelin ratio increased during the surfactant-induced remission of respiratory failure, decreased during the relapse of respiratory failure (present among 50% of the surfactant-treated infants), and increased again during the recovery. The control infants tended to have lower saturated phosphatidylcholine/sphingomyelin ratios during the first week than the surfactant-treated infants. Therecipients of surfactant had slightly more severe lung disease than the controls, when the results were adjusted by covariance to remove the differences in the saturated phosphatidylcholine/sphingomyelin ratio. Exogenous surfactant increased the amarent endogenous ~o o l size at least fivefold. The apparent half-life of ~hosph~tidylglycerol was 30 h (20-36 h). The half-life was independent of the amount of exogenous surfactant (60 versus 120 n~g/kg). Therefore, the apparent turnover rate after 120 was higher than after 60 mg/kg surfactant (p < 0.01).

show abstract

Rates of replacement of lecithins and alveolar instability in rat lungs

Cited by 132 publications

References 0 publications

Metabolism of Exogenously Administered Natural Surfactant in the Newborn Lamb

Metabolism of Exogenously Administered Natural Surfactant in the Newborn Lamb

Lecithin Appearance and Apparent Biologic Half-Life in Term Newborn Rabbit Lung

Effect of Surfactant Substitution on Lung Effluent Phospholipids in Respiratory Distress Syndrome: Evaluation of Surfactant Phospholipid Turnover, Pool Size, and the Relationship to Severity of Respiratory Failure

Contact Info

Product

Resources

About