elastin and Bronchopulmonary-Dysplasia

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that occurs in very premature infants and is characterized by impaired alveologenesis. This ultimate phase of lung development is mostly postnatal and allows growth of gas-exchange surface area to meet the needs of the organism. Alveologenesis is a highly integrated process that implies cooperative interactions between interstitial, epithelial, and vascular compartments of the lung. Understanding of its underlying mechanisms has considerably progressed recently with identification of structural, signaling, or remodeling molecules that are crucial in the process. Thus, the pivotal role of elastin deposition in lung walls has been demonstrated, and many key control-molecules have been identified, including various transcription factors, growth factors such as platelet-derived growth factor, fibroblast growth factors, and vascular endothelial growth factor, matrix-remodeling enzymes, and retinoids. BPD-associated changes in lung expression/content have been evidenced for most of these molecules, especially for signaling pathways, through both clinical investigations in premature infants and the use of animal models, including the premature baboon or lamb, neonatal exposure to hyperoxia in rodents, and maternal-fetal infection. These findings open therapeutic perspectives to correct imbalanced signaling. Unraveling the intimate molecular mechanisms of alveolar building appears as a prerequisite to define new strategies for the prevention and care of BPD.

Topics: Animals; Bronchopulmonary Dysplasia; Cell Differentiation; Cell Proliferation; Elastin; Fibroblast Growth Factors; Humans; Hypoxia; Infant, Newborn; Lung; Models, Biological; Platelet-Derived Growth Factor; Premature Birth; Pulmonary Alveoli; Pulmonary Gas Exchange; Retinoids; Signal Transduction; Vascular Endothelial Growth Factor A

Topics: Animals; Bronchopulmonary Dysplasia; Calcium-Binding Proteins; Cell Differentiation; Cells, Cultured; EGF Family of Proteins; Elastin; Extracellular Matrix Proteins; Fibrillin-1; Humans; Mice; Mice, Knockout; Myofibroblasts; Protein-Lysine 6-Oxidase; Pulmonary Alveoli; Receptor, Platelet-Derived Growth Factor alpha; RNA, Messenger; Transforming Growth Factor beta1

The incidence and mortality rates of bronchopulmonary dysplasia (BPD) remain very high. Therefore, novel therapies are imminently needed to improve the outcome of this disease. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) show promising therapeutic effects on oxygen-induced model of BPD. In our experiment, UC-MSCs were intratracheally delivered into the newborn rats exposed to hyperoxia, a well-established BPD model. This study demonstrated that UC-MSCs reduce elastin expression stimulated by 90% O

Topics: Animals; Animals, Newborn; Bronchopulmonary Dysplasia; Cells, Cultured; Cord Blood Stem Cell Transplantation; Elastin; Humans; Hyperbaric Oxygenation; Hyperoxia; Lung; Lung Injury; Mesenchymal Stem Cell Transplantation; Rats; Rats, Sprague-Dawley; Treatment Outcome

Although high-mobility group box-1 (HMGB1) levels in tracheal aspirates are associated with the pathological features of bronchopulmonary dysplasia (BPD), the role of HMGB1 in the terminal stage of abnormal alveologenesis has not yet been understood. In this study, we addressed the role of HMGB1 in the elastogenesis disruption in the lungs of newborn mice with BPD. We found that elevations of whole lung HMGB1 level were associated with impaired alveolar development and aberrant elastin production in 85% O2-exposed lungs. HMGB1 neutralizing antibody attenuated the structural disintegration developed in hyperoxia-damaged lungs. Furthermore, HMGB1 inhibition rescued the neutrophil influx in hyperoxia-injured lung and partially abolished the mRNA level of the proinflammatory mediators, interleukin (IL)-1β and transforming growth factor (TGF)-β1. These data suggested that pulmonary HMGB1 plays an important role in the disruption of elastogenesis in the terminal stage of lung development through reduced pulmonary inflammatory response.

Topics: Animals; Animals, Newborn; Antibodies, Neutralizing; Bronchopulmonary Dysplasia; Disease Models, Animal; Elastin; Gene Expression Regulation, Developmental; HMGB1 Protein; Humans; Hyperoxia; Interleukin-1beta; Mice; Mice, Inbred C57BL; Neutrophils; Oxygen; Pulmonary Alveoli; Transforming Growth Factor beta1

Mechanical ventilation is an important risk factor for development of bronchopulmonary dysplasia. Here we investigated the effects of different tidal volumes (VT) and duration of ventilation on expression of genes involved in alveolarization [tropoelastin (Eln), lysyloxidase-like 1 (Loxl1), fibulin5 (Fbln5), and tenascin-C (Tnc)] and angiogenesis [platelet derived growth factors (Pdgf) and vascular endothelial growth factors (Vegf) and their receptors] in 8-day-old rats. First, pups were ventilated for 8 h with low (LVT: 3.5 ml/kg), moderate (MVT: 8.5 ml/kg), or high (HVT: 25 ml/kg) tidal volumes. LVT and MVT decreased Tnc expression, whereas HVT increased expression of all three elastogenic genes and Tnc. PDGF α-receptor mRNA was increased in all ventilation groups, while Pdgfb expression was decreased after MVT and HVT ventilation. Only HVT ventilation upregulated Vegf expression. Independent of VT, ventilation upregulated Vegfr1 expression, while MVT and HVT downregulated Vegfr2 expression. Next, we evaluated duration (0-24 h) of MVT ventilation on gene expression. Although expression of all elastogenic genes peaked at 12 h of ventilation, only Fbln5 was negatively affected at 24 h. Tnc expression decreased with duration of ventilation. Changes in expression of Pdgfr and Vegfr were maximal at 8 h of ventilation. Disturbed elastin fiber deposition and decrease in small vessel density was only observed after 24 h. Thus, an imbalance between Fbln5 and Eln expression may trigger dysregulated elastin fiber deposition during the first 24 h of mechanical ventilation. Furthermore, ventilation-induced alterations in Pdgf and Vegf receptor expression are tidal volume dependent and may affect pulmonary vessel formation.

Topics: Amino Acid Oxidoreductases; Animals; Animals, Newborn; Biosynthetic Pathways; Bronchopulmonary Dysplasia; Elastin; Extracellular Matrix Proteins; Gene Expression; Neovascularization, Physiologic; Platelet-Derived Growth Factor; Pulmonary Alveoli; Rats, Wistar; Recombinant Proteins; Respiration, Artificial; Tenascin; Vascular Endothelial Growth Factor A

Maturation of the lung extracellular matrix (ECM) plays an important role in the formation of alveolar gas exchange units. A key step in ECM maturation is cross-linking of collagen and elastin, which imparts stability and functionality to the ECM. During aberrant late lung development in bronchopulmonary dysplasia (BPD) patients and animal models of BPD, alveolarization is blocked, and the function of ECM cross-linking enzymes is deregulated, suggesting that perturbed ECM cross-linking may impact alveolarization. In a hyperoxia (85% O2)-based mouse model of BPD, blunted alveolarization was accompanied by alterations to lung collagen and elastin levels and cross-linking. Total collagen levels were increased (by 63%). The abundance of dihydroxylysinonorleucine collagen cross-links and the dihydroxylysinonorleucine-to-hydroxylysinonorleucine ratio were increased by 11 and 18%, respectively, suggestive of a profibrotic state. In contrast, insoluble elastin levels and the abundance of the elastin cross-links desmosine and isodesmosine in insoluble elastin were decreased by 35, 30, and 21%, respectively. The lung collagen-to-elastin ratio was threefold increased. Treatment of hyperoxia-exposed newborn mice with the lysyl oxidase inhibitor β-aminopropionitrile partially restored normal collagen levels, normalized the dihydroxylysinonorleucine-to-hydroxylysinonorleucine ratio, partially normalized desmosine and isodesmosine cross-links in insoluble elastin, and partially restored elastin foci structure in the developing septa. However, β-aminopropionitrile administration concomitant with hyperoxia exposure did not improve alveolarization, evident from unchanged alveolar surface area and alveoli number, and worsened septal thickening (increased by 12%). These data demonstrate that collagen and elastin cross-linking are perturbed during the arrested alveolarization of developing mouse lungs exposed to hyperoxia.

Topics: Aminopropionitrile; Animals; Bronchopulmonary Dysplasia; Collagen; Elastin; Extracellular Matrix; Hyperoxia; Lung; Mice; Protein Processing, Post-Translational; Protein-Lysine 6-Oxidase

Because therapeutic options are lacking for bronchopulmonary dysplasia (BPD), there is an urgent medical need to discover novel targets/drugs to treat this neonatal chronic lung disease. Metformin, a drug commonly used to lower blood glucose in type 2 diabetes patients, may be a novel therapeutic option for BPD by reducing pulmonary inflammation and fibrosis and improving vascularization. We investigated the therapeutic potential of daily treatment with 25 and 100 mg/kg metformin, injected subcutaneously in neonatal Wistar rats with severe experimental BPD, induced by continuous exposure to 100% oxygen for 10 days. Parameters investigated included survival, lung and heart histopathology, pulmonary fibrin and collagen deposition, vascular leakage, right ventricular hypertrophy, and differential mRNA expression in the lungs of key genes involved in BPD pathogenesis, including inflammation, coagulation, and alveolar development. After daily metformin treatment rat pups with experimental BPD had reduced mortality, alveolar septum thickness, lung inflammation, and fibrosis, demonstrated by a reduced influx of macrophages and neutrophils and hyperoxia-induced collagen III and fibrin deposition (25 mg/kg), as well as improved vascularization (100 mg/kg) compared with control treatment. However, metformin did not ameliorate alveolar enlargement, small arteriole wall thickening, vascular alveolar leakage, and right ventricular hypertrophy. In conclusion metformin prolongs survival and attenuates pulmonary injury by reducing pulmonary inflammation, coagulation, and fibrosis but does not affect alveolar development or prevent pulmonary arterial hypertension and right ventricular hypertrophy in neonatal rats with severe hyperoxia-induced experimental BPD.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents; Bronchopulmonary Dysplasia; Capillary Permeability; Collagen; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Elastin; Fibrin; Gene Expression; Hypertrophy, Right Ventricular; Lung; Metformin; Rats, Wistar

Nitric oxide (NO) plays an important role in lung development and perinatal lung function, and pulmonary NO synthases (NOS) are decreased in bronchopulmonary dysplasia (BPD) following preterm birth. Fetal estradiol levels increase during late gestation and estradiol up-regulates NOS, suggesting that after preterm birth estradiol deprivation causes attenuated lung NOS resulting in impaired pulmonary function.. To test the effects of postnatal estradiol administration in a primate model of BPD over 14 days after delivery at 125 days of gestation (term = 185 d).. Cardiopulmonary function was assessed by echocardiography and whole body plethysmography. Lung morphometric and histopathologic analyses were performed, and NOS enzymatic activity and abundance were measured.. Estradiol caused an increase in blood pressure and ductus arteriosus closure. Expiratory resistance and lung compliance were also improved, and this occurred before spontaneous ductal closure. Furthermore, both oxygenation and ventilation indices were improved with estradiol, and the changes in lung function and ventilatory support requirements persisted throughout the study period. Whereas estradiol had negligible effect on indicators of lung inflammation and on lung structure assessed after the initial 14 days of ventilatory support, it caused an increase in lung neuronal and endothelial NOS enzymatic activity.. In a primate model of BPD, postnatal estradiol treatment had favorable cardiovascular impact, enhanced pulmonary function, and lowered requirements for ventilatory support in association with an up-regulation of lung NOS. Estradiol may be an efficacious postnatal therapy to improve lung function and outcome in preterm infants.

Topics: Animals; Animals, Newborn; Blood Pressure; Bronchoalveolar Lavage Fluid; Bronchopulmonary Dysplasia; Disease Models, Animal; Ductus Arteriosus; Elastin; Estradiol; Estrogens; Female; Humans; Infant, Newborn; Lung; Lung Compliance; Male; Nitric Oxide Synthase; Oxygen; Papio; Pulmonary Surfactants; Random Allocation; Receptors, Estradiol; Respiration, Artificial; RNA, Messenger; Up-Regulation

Preterm infants are at high risk of developing ventilator-induced lung injury (VILI), which contributes to bronchopulmonary dysplasia. To investigate causes of VILI, we have developed an animal model of in utero ventilation (IUV). Our aim was to characterize the effects of IUV on the very immature lung, in the absence of nonventilatory factors that could contribute to lung pathology. Fetal sheep were ventilated in utero at 110 d gestation for 1, 6, or 12 h (two groups; n = 5 each). Lung tissue was collected at 12 h after initiating IUV in the 1, 6, and one 12 h IUV groups. Lung liquid was replaced in the second 12 h IUV group and tissues collected at 117 d. Operated, nonventilated 110 and 117 d fetuses were controls. IUV reduced secondary septal crest densities, simplified distal airsacs, caused abnormal collagen and elastin deposition, and stimulated myofibroblast differentiation and cellular proliferation. IUV causes VILI in very immature lungs in the absence of other complicating factors and reproduces bronchopulmonary dysplasia -like changes in lung morphology. IUV offers a novel method for dissociating VILI from other iatrogenic factors that could contribute to altered lung development caused by VILI.

Topics: Animals; Bronchopulmonary Dysplasia; Cell Differentiation; Elastin; Fetus; Fibroblasts; Humans; Immunohistochemistry; Infant, Newborn; Models, Animal; Sheep; Time Factors; Ventilator-Induced Lung Injury

All-trans retinoic acid (RA) is a potent modulator of lung development. Chorioamnionitis, which is frequently associated with preterm birth, causes fetal lung inflammation and improves lung function but also results in alveolar simplification and microvascular injury. Endotoxin-mediated chorioamnionitis reduces RA concentration in the fetal lung to 16% of control values. We hypothesized that administration of RA to the fetus before induction of chorioamnionitis would preserve septation of the distal airspaces. Time-mated ewes with singletons were assigned to receive a fetal intramuscular treatment with 20,000 IU of RA in olive oil (or olive oil only) 3 hr prior to intra-amniotic injection of endotoxin (20 mg, E. coli 055:B5) or saline, at 124-day gestational age and 7 days after the fetal treatment. The right cranial lung lobe was processed for morphometric analysis. RA treatment did not affect chorioamnionitis-induced fetal and systemic inflammation or interleukin-8 concentrations in lung tissue. RA administration alone did not alter lung structure. Relative to control lungs (5 +/- 3 mL/kg), lung volume increased similarly with endotoxin (22 +/- 4 mL/kg) or RA plus endotoxin (20 +/- 3 mL/kg; P < 0.05). Alveolar wall thickness was 4.2 +/- 0.3 mum after endotoxin-induced chorioamnionitis, 6.0 +/- 0.4 mum in controls (P < 0.05 versus endotoxin) and 5.5 +/- 0.2 mum after RA and endotoxin (P < 0.05 versus control, n.s. versus endotoxin). The ratio of airspace versus tissue was 4.6 +/- 0.3 in endotoxin-induced chorioamnionitis, 2.1 +/- 0.3 in controls and 4.1 +/- 0.5 after RA and endotoxin. We conclude that fetal treatment with RA did not prevent inflammation-induced alveolar simplification.

Topics: Animals; Bronchopulmonary Dysplasia; Chorioamnionitis; Disease Models, Animal; Elastin; Endotoxins; Female; Fetus; Humans; Infant, Newborn; Interleukin-8; Lung; Pregnancy; Pulmonary Alveoli; Sheep; Tretinoin

Pulmonary inflammation and increased production of the inflammatory cytokine IL-1beta are associated with the development of bronchopulmonary dysplasia (BPD) in premature infants. To study the actions of IL-1beta in the fetal and newborn lung in vivo, we developed a bitransgenic mouse in which IL-1beta is expressed under conditional control in airway epithelial cells. Perinatal pulmonary expression of IL-1beta caused respiratory insufficiency that was associated with increased postnatal mortality. While intrauterine growth of IL-1beta-expressing mice was normal, their postnatal growth was impaired. IL-1beta disrupted alveolar septation and caused abnormalities in alpha-smooth muscle actin and elastin deposition in the septa of distal airspaces. IL-1beta disturbed capillary development and inhibited the production of vascular endothelial growth factor in the lungs of infant mice. IL-1beta induced the expression of CXC chemokines KC (CXCL1) and macrophage inflammatory protein-2 (CXCL2) and of CC chemokines monocyte chemotactic protein (MCP)-1 (CCL2) and MCP-3 (CCL7), consistent with neutrophilic and monocytic infiltration of the lungs. IL-1beta caused goblet cell metaplasia and bronchial smooth muscle hyperplasia. Perinatal expression of IL-1beta in epithelial cells of the lung caused a lung disease that was clinically and histologically similar to BPD.

Topics: Actins; Animals; Animals, Newborn; Bronchopulmonary Dysplasia; Chemokine CCL2; Chemokine CCL7; Chemokine CXCL1; Chemokines, CXC; Disease Models, Animal; Elastin; Epithelial Cells; Humans; Infant, Newborn; Interleukin-1beta; Lung; Mice; Mice, Transgenic; Monocyte Chemoattractant Proteins; Vascular Endothelial Growth Factor A

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that adversely affects long-term pulmonary function as well as neurodevelopmental outcomes of preterm infants. Elastolytic proteases have been implicated in the pathogenesis of BPD. Cathepsin S (cat S) is a cysteine protease with potent elastolytic activity. Increased levels and activity of cat S have been detected in a baboon model of BPD.. To investigate whether deficiency of cat S alters the course of hyperoxia-induced neonatal lung injury in mice.. Newborn wild-type and cat S-deficient mice were exposed to 80% oxygen for 14 days. Histologic and morphometric analysis were performed and bronchoalveolar lavage protein and cells were analyzed. Lung elastin was assessed by real-time polymerase chain reaction, in situ hybridization, desmosine analysis, and Hart's stain. Distribution of myofibroblasts was analyzed by immunofluorescence. Hydroxyproline content of lung tissues was measured.. Hyperoxia-exposed cat S-deficient mice were protected from growth restriction and had improved alveolarization, decreased septal wall thickness, lower number of macrophages, and lower protein concentration in bronchoalveolar lavage fluid. alpha-Smooth muscle actin-expressing myofibroblasts accounted for at least some of the increased interstitial cellularity in hyperoxia-exposed mouse lungs and were significantly less in cat S-deficient lungs. Lung hydroxyproline content was increased in hyperoxia-exposed wild-type, but not in cat S-deficient lungs. Desmosine content was significantly reduced in both genotypes with hyperoxia.. Cathepsin S deficiency improves alveolarization, and attenuates macrophage influx and fibroproliferative changes in hyperoxia-induced neonatal mouse lung injury.

Topics: Animals; Animals, Newborn; Bronchoalveolar Lavage Fluid; Bronchopulmonary Dysplasia; Cathepsins; Collagen; Desmosine; Disease Models, Animal; Elastin; Humans; Hydroxyproline; Hyperoxia; Infant, Newborn; Lung; Lung Injury; Macrophages, Alveolar; Mice; Proteins; Pulmonary Alveoli; RNA, Messenger

Topics: Animals; Animals, Newborn; Bronchopulmonary Dysplasia; Elastin; Humans; Infant, Newborn; Models, Animal; Pulmonary Alveoli; Sheep; Vitamin A

Hypolastic lung in congenital diaphragmatic hernia (CDH) shows markedly thickened alveolar walls, increased interstitial tissue, and markedly diminished alveolar air space, showing morphologic immaturity. Decrease in lung compliance and distensibility often is seen in human CDH as well as experimentally produced CDH. Collagen and elastin, critical components of the lung connective tissue, have been suggested to have important influence on lung compliance and maximal expansion. The barotrauma caused by mechanical ventilation is known to produce structural changes in the pulmonary architecture. The aim of this study was to investigate the expression and production of elastin in the lung in newborn rats with CDH during mechanical ventilation.. CDH was induced in rat embryos after administration of nitrofen to pregnant dams on day 9.5 of gestation. Cesarean section was performed on day 21 of gestation. The newborn rats were intubated using a 24-gauge Teflon catheter. After ligation of the umbilical cord, the intubated animals were transferred immediately to a warm plate and connected to a modified ventilator. Ventilation was continued for a maximum of 6 hours. The relative amount of soluble elastin in the lung was assessed using an enzyme-linked immunosorbent assay (ELISA) technique. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the relative amount of tropoelastin mRNA expression in the lung.. Elastin mRNA in the CDH lung was increased significantly (P <.01) at one hour after ventilation compared with ventilated controls. Elastin protein significantly increased in the CDH lung at one hour (P <.01) and 6 hours (P <.01) after starting ventilation compared with controls.. The data show that during mechanical ventilation, elastin production is increased significantly in the CDH lung, and this may further affect lung compliance.

Topics: Animals; Animals, Newborn; Bronchopulmonary Dysplasia; Culture Techniques; Elastin; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression; Hernia, Diaphragmatic; Humans; Infant, Newborn; Lung; Lung Compliance; Phenyl Ethers; Pregnancy; Rats; Rats, Sprague-Dawley; Respiration, Artificial; Reverse Transcriptase Polymerase Chain Reaction; Tropoelastin

Prolonged mechanical ventilation of premature neonates is often associated with abnormal morphological development of the lung and chronic lung disease, sometimes called bronchopulmonary dysplasia (BPD). Impaired alveolar development is a hallmark of this disease. To better understand the effects of mechanical ventilation on lung elastin expression, we studied lung tissue from 10 preterm lambs (gestation = 125 days; term = 148 days) mechanically ventilated for 3-4 wk at a respirator rate of 20 breaths/min and tidal volume of 15 +/- 5 ml/kg (n = 5) or 60 breaths/min and tidal volume of 5 +/- 2 ml/kg (n = 5). Histopathology showed increased elastin accumulation and abnormal morphological development in the ventilated groups. Postmortem lung desmosine content was increased significantly in the 20 breaths/min group. Tropoelastin mRNA expression was increased in both ventilated groups. In situ hybridization localized increased tropoelastin mRNA expression to sites of accumulated elastin in extended alveolar walls with scant, attenuated secondary crests. Lung collagen content, as assessed by the amount of hydroxyproline in lung tissue, was similar to controls. These data suggest that excessive production and accumulation of elastin is associated with chronic lung injury from prolonged mechanical ventilation after premature birth.

Topics: Animals; Bronchopulmonary Dysplasia; Collagen; Elastin; Extracellular Matrix; Humans; In Situ Hybridization; Infant, Newborn; Infant, Premature; Lung; Respiration, Artificial; RNA, Messenger; Sheep; Tropoelastin

Terminal gas-exchange units in the lung of many species are, at birth, relatively large structures termed saccules. Saccules septate postnatally forming smaller units that constitute the final alveoli. In the rat, septation occurs intensively during the first 2 postnatal wk after which it has been considered to stop. Treatment with dexamethasone or exposure to hyperoxia during the first 2 postnatal wk markedly inhibits septation as evidenced by the formation of fewer and bigger alveoli than in normally developed rats. Deferoxamine, an iron chelator, has been reported to protect the lung from the effects of exposure to hyperoxia in early postnatal life. In this study, we investigated the effects of these treatments during the 3rd and 4th postnatal wk, that is, after the early period of rapid alveolarization. Our results show that treatment with dexamethasone no longer had any inhibitory effect on alveoli formation; that exposure to hyperoxia continued to inhibit the formation of new alveoli, resulting in bigger and less numerous alveoli; that treatment of animals exposed to hyperoxia with deferoxamine still protected their lungs against hyperoxic inhibition; and that elastin fiber length density in the lung was significantly reduced in hyperoxic-exposed animals. These results suggest that septation continues beyond the 2nd postnatal wk and does not stop abruptly at age 14 d in air-breathing rats and that hyperoxic inhibition of alveolarization during the 3rd and 4th postnatal wk is due to the inhibition of septation of existing or newly generated gas-exchange units during that period of lung development.

Topics: Age Factors; Animals; Bronchopulmonary Dysplasia; Deferoxamine; Dexamethasone; Elastin; Humans; Infant, Newborn; Lung Volume Measurements; Oxygen; Pulmonary Alveoli; Pulmonary Gas Exchange; Rats; Rats, Sprague-Dawley

In order to determine whether elastin degradation is increased in infants whose respiratory insufficiency requires ventilation with high concentrations of O2, we quantitated, by amino acid analysis, the elastin degradation products (desmosines) excreted in the urine of 14 premature male infants during the first 3 wk of life. Eight of these infants, the "low-O2" infants, did not have severe lung disease and did not require more than 40% O2 beyond the first 8 h of life. The other 6 infants, selected retrospectively because they developed bronchopulmonary dysplasia (BPD), were ventilated with more than 60% O2 for at least the first 72 h of life. The pattern of desmosine excretion observed in infants who developed BPD differed significantly (p less than 0.05) from the excretion pattern seen in "low-O2" infants during the first 3 wk of life. At the end of the first week of life, desmosine excretion was significantly greater (p less than 0.05) in the infants who later developed BPD than in the "low-O2" infants without severe lung disease. From Days 7-9 to 20-22, desmosine excretion increased in the "low-O2" infants from 6.9 +/- 1.7 micrograms/kg to 9.0 +/- 3.5 micrograms/kg. In contrast, desmosine excretion did not remain elevated in the BPD infants, decreasing from 10.6 +/- 2.2 micrograms/kg to 6.1 +/- 2.9 micrograms/kg during the same period. In the BPD infants, elevated desmosine excretion through Day 9 is likely to reflect lung injury, whereas decreased desmosine excretion beyond Day 9 suggests that elastin synthesis and turnover is impaired, possibly as a result of nutritional deficiencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Age Factors; Bronchopulmonary Dysplasia; Desmosine; Elastin; Humans; Infant, Newborn; Infant, Premature, Diseases; Isodesmosine; Male; Oxygen Inhalation Therapy