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PubMed1989

High tidal volume ventilation produces increased lung water in oleic acid-injured rabbit lungs.

Repeated lung inflation with very high tidal volumes (VT) is associated with the production of permeability pulmonary edema in animal models using previously normal lungs. We studied the effect of mechanical ventilation, at VT values approaching those used clinically, on lung weight gain (lung water) in salt-perfused rabbit lungs diffusely injured by the administration of oleic acid. Lungs ventilated at a VT of 18 ml/kg gained significantly more weight at 30 through 90 min than did lungs ventilated at 6 ml/kg. These differences in weight gain were not associated with differences in the evolution of thromboxane B2 in the perfusate. The impact of VT on lung water and outcome in patients with lung injury deserves further study.

Animals↗
PubMed2001

High-frequency oscillatory ventilation of the perfluorocarbon-filled lung: dose-response relationships in an animal model of acute lung injury.

OBJECTIVE: To examine dose-response relationships regarding the efficiency of gas exchange and hemodynamic function during high-frequency oscillation and partial liquid ventilation (HFO-PLV) of the perfluorocarbon (PFC)-treated lung in a model of acute lung injury. SETTING: An animal research laboratory in a university medical center. DESIGN: A prospective, randomized study comparing animals receiving varying doses (0, 5, 15, and 20 mL/kg) of perflubron during high-frequency oscillatory ventilation (HFOV) with mean airway pressure (Paw) optimized to achieve a minimal percutaneous oxygen saturation (Spo2). SUBJECTS: Nineteen healthy swine (mean weight 28.9 kg) with saline lavage-induced acute lung injury. METHODS: Animals were treated with repetitive saline lavage to achieve a uniform degree of acute lung injury (Spo2 < or =90% on an Fio2 of 1.0). After lung injury, subjects were converted to HFOV, and lung volume was optimized. HFO-PLV was initiated by instillation of perflubron at a rate of 0.5 mL.kg-1.min-1 to achieve total doses of 5, 15, and 20 mL/kg. After PFC dosing, the only experimental manipulation consisted of adjustment of Paw to achieve an Spo2 of 90% +/- 2% with Fio2 of 0.6. Gas exchange, hemodynamic variables, and pulmonary mechanics data were collected over a 1-hr period. Five control animals were not dosed with perflubron and remained on HFOV for the 1-hr period of data collection. MEASUREMENTS AND MAIN RESULTS: After lung volume recruitment with HFOV, the initiation of HFO-PLV was best tolerated with the two lower doses in our protocol. There were essentially no changes in Paco2 or pH between groups over the dosing interval. After dosing, analysis of variance demonstrated a PFC dose-dependent effect for oxygenation index (p =.01) only; the lowest oxygenation index was found in the 15 mL/kg group (p =.01). In the 15 mL/kg group, the Paw decreased steadily from 20.6 +/- 3.4 cm H2O at the end of dosing to 18.0 +/- 4.9 cm H2O at 60 mins. The Pao2 increased from 113 +/- 51 torr (15.06 +/- 6.79 kPa) to 134 +/- 49 torr (17.86 +/- 6.53 kPa) during this period and was associated with a decreasing oxygenation index (from 11.4 +/- 2.0 to 9.3 +/- 1.5). The cardiac index and pulmonary vascular resistance did not change significantly during the dosing period and were relatively stable after the completion of dosing. CONCLUSIONS: The combination of HFOV and perflubron administration was well tolerated hemodynamically and was not associated with deterioration of gas exchange during dosing. Our data suggest that the optimal dose of perflubron to achieve the lowest oxygenation index during HFO-PLV is between 5 and 15 mL/kg. The combination of HFOV and perflubron administration is a novel strategy in the treatment of acute lung injury that shows some promise and merits additional investigation. We hope in future studies to address the histopathologic effects of varying perflubron doses during HFOV in a long-term study of the lung-protective effects of HFO-PLV.

Animals↗
PubMed2003

Comparison of quantitative 99mTc-HMPAO and 67Ga citrate lung scans in patients with active diffuse infiltrative lung disease.

Diffuse infiltrative lung disease (ILD) is a heterogeneous group of disorders that predominantly affect the lung parenchyma and spare the airway. To objectively assess the degree of pulmonary vascular endothelium damage in active ILD, lung/liver uptake ratios (L/L ratios) on 99mTc hexamethylpropylene amine oxime (99mTc-HMPAO) lung scans were determined in 21 patients with active ILD. Meanwhile, the 67Ga citrate uptake index (GUI) on 67Ga lung scans was measured in order to evaluate the severity of lung inflammation in active ILD. The results show there were statistically significant differences between normal controls and patients with active ILD, as shown in the L/L ratio and GUI. However, when the patients were divided into two groups: (1) eight patients with normal chest X-ray findings, and (2) 13 patients with abnormal X-ray findings, there was no significant difference between groups 1 and 2 for the results of L/L ratio and GUI. In addition, no correlation between the degree of damage to the pulmonary vascular endothelium and the severity of lung inflammation was found. In conclusion, L/L ratios on 99mTc-HMPAO lung scans and GUI on 67Ga lung scans are different to the findings of chest X-rays and have the potential to objectively detect the degree of damage to the pulmonary vascular endothelium and the severity of lung inflammation in active IDL. However, the relationship between L/L ratio and GUI in active ILD is not significant.

Acute Disease↗
PubMed2007

Nonischemic lung injury by mediators from unilateral ischemic reperfused lung: ameliorating effect of tumor necrosis factor-alpha-converting enzyme inhibitor.

We hypothesized that the ischemic reperfused (I/R) lung expresses and liberates tumor necrosis factor-alpha (TNF-alpha) to injure the nonischemic lung, and that a TNF-alpha-converting enzyme inhibitor (TACEI) prevents injury of the nonischemic lung by blocking TNF-alpha liberation from the I/R lung. In isolated ventilated rat lungs in which differential perfusion to the right (RL) or left (LL) lung was feasible, LLs were selectively made ischemic (60 min) while maintaining perfusion to RLs, then reperfused (30 min) in a nonrecirculating manner with buffer solution (non-R; n = 18) or in a recirculating manner with buffer containing TACEI (TACEI[+]; n = 18) or without TACEI (TACEI[-]; n = 18). Ischemia reperfusion induced TNF-alpha messenger RNA expression in the ischemic LLs; the expression was highest in TACEI(+) group (P < 0.01). The expression of TNF-alpha, which was detected as immunofluorescence signals on CD34-positive endothelial cells, was observed in ischemic LLs; the highest expression being that in the TACEI(+) group. Wet/dry ratio and protein content in bronchoalveolar lavage fluid were higher in LLs than in RLs, and among the RLs, these 2 parameters were significantly increased in the TACEI(-) group (P < 0.01) in which the RLs were exposed to the TNF-alpha-rich perfusate. On the other hand, protein content in bronchoalveolar lavage fluid of the TACEI(+) group in which RLs were exposed to recirculating perfusate containing little TNF-alpha was decreased to a level close to but still higher than that in the non-R group (P < 0.05). The unilateral I/R lung affected the permeability of the nonischemic lung by liberating mainly TNF-alpha and induced TNF-alpha, interleukin (IL)-1beta, IL-6, and IL-10 messenger RNA expression in the nonischemic lung. These findings support the idea of organ-organ interaction in which an injured organ affects a remote organ by liberating humoral mediators.

ADAM Proteins↗
PubMed1999

The changes in magnetic resonance properties of the fetal lungs: a first result and a potential tool for the non-invasive in utero demonstration of fetal lung maturation.

OBJECTIVE: To measure magnetic resonance parameters T1 and T2 of the fetal lungs and investigate the relationship of these parameters to changes in volume and gestation. DESIGN: Prospective cross-sectional study. SETTING: Large teaching hospital in Nottingham and the Magnetic Resonance Centre at the University of Nottingham. POPULATION: Normal pregnancies from 20 weeks to term. METHODS: T1, T2, and lung volume were measured in the fetus using echo-planar magnetic resonance imaging. MAIN OUTCOME MEASURES: The relationship of T1 and T2 to gestational age and lung volume. RESULTS: Linear regression demonstrated a significant relationship (P < 0.001) between gestational age and lung volume, T1 and T2. There was also a significant relationship between lung volume and T1 and T2 (P < 0-001). CONCLUSIONS: Relaxation time measurements give additional information to lung volume estimation in the assessment of lung physiology in utero. We have demonstrated the progressive changes which take place in the fetal lungs between 20 weeks and term. The physiological changes which can be demonstrated with this non-invasive technique may have an important application in the demonstration of fetal lung maturity in a prospective non-invasive manner.

Cross-Sectional Studies↗
PubMed1995

Virulence ranking of some Mycobacterium tuberculosis and Mycobacterium bovis strains according to their ability to multiply in the lungs, induce lung pathology, and cause mortality in mice.

Three virulent strains of Mycobacterium tuberculosis (H37Rv, Erdman, and NYH-27) and two virulent strains of M. bovis (Ravenel and Branch) were compared in terms of their growth rates in the livers and the lungs of mice, their ability to cause lung pathology, and the time taken for them to cause death. In immunocompetent mice, all strains caused an infection that progressed for 20 days or more and then underwent resolution in the liver but not in the lungs. In the lungs, infection persisted and induced progressive pathology. According to host survival time, Ravenel was the most virulent strain, followed, in decreasing order of virulence, by Branch, H37Rv, Erdman, and NYH-27. The much longer survival times of mice infected with M. tuberculosis strains allowed time for lung histopathology to change from a histiocytic alveolitis to a chronic fibroblastic fibrosis that eventually obliterated most of the lung architecture. By contrast, in mice infected with M. bovis strains, the alveolitis that developed during early infection was rapid and expansive enough to cause death before chronic lung pathology became evident. In mice depleted of CD4+ T cells, increased growth of all virulent strains induced necrotic exudative lung lesions that rapidly filled most of the alveolar sacs with inflammatory cells. These mice died much earlier than infected control mice did. Attenuated strains had longer population doubling times in vivo and failed to cause progressive disease or pathology in the lungs or livers of immunocompetent mice.

Animals↗
PubMed1991

Effect of single lung transplantation on pulmonary hypertension in patients with end stage fibrosing lung disease.

OBJECTIVE: To investigate the effect of successful single lung transplantation on pulmonary haemodynamic variables and right ventricular function. DESIGN: Pulmonary haemodynamic variables and right ventricular function were measured at right heart catheterisation after single lung transplantation. The results were compared with the preoperative pulmonary haemodynamic variables measured at the time of assessment for transplantation. SETTING: A tertiary referral centre. PATIENTS: Five survivors of single lung transplantation performed for end stage lung disease. INTERVENTIONS: Cardiac catheterisation in all five patients at a mean of 18 months postoperatively. Preoperative catheter data were available for comparison in four. Right heart pressures and cardiac output were measured and right ventricular angiography was performed. Perfusion scans performed for clinical reasons were used to assess the percentage of cardiac output passing through each lung. MAIN OUTCOME MEASURES: Right heart pressures, cardiac output, right ventricular function, percentage perfusion to lungs. RESULTS: After operation mean peak right ventricular pressure fell from 53 mm Hg to 33 mm Hg, mean pulmonary artery pressure from 33 mm Hg to 18 mm Hg, total pulmonary resistance from 11.2 U x m2 to 5.8 U x m2, and pulmonary arteriolar resistance from 8.9 U x m2 to 3.6 U x m2. Pulmonary artery wedge pressure and cardiac index were unchanged. Right ventricular function improved in all patients. The transplanted lung received most of the cardiac output. CONCLUSION: In patients with moderate pulmonary hypertension and right ventricular dysfunction secondary to end stage fibrosing lung disease single lung transplantation was followed by an improvement in pulmonary haemodynamic variables and right ventricular function.

Blood Pressure↗
PubMed2002

Cross sectional study on lung function of coke oven workers: a lung function surveillance system from 1978 to 1990.

AIMS: To determine the association between lung function of coke oven workers and exposure to coke oven emissions. METHODS: Lung function data and detailed work histories for workers in recovery coke ovens of a steelworks were extracted from a lung function surveillance system. Multiple regressions were employed to determine significant predictors for lung function indices. The first sets of lung function tests for 613 new starters were pooled to assess the selection bias. The last sets of lung function tests for 834 subjects with one or more year of coke oven history were pooled to assess determinants of lung function. RESULTS: Selection bias associated with the recruitment process was not observed among the exposure groups. For subjects with a history of one or more years of coke oven work, each year of working in the most exposed "operation" position was associated with reductions in FEV(1) of around 9 ml (p = 0.006, 95% CI: 3 ml to 16 ml) and in FVC of around 12 ml (p = 0.002, 95% CI: 4 ml to 19 ml). Negative effects of smoking on lung function were also observed. CONCLUSIONS: Exposure to coke oven emissions was found to be associated with lower FEV(1) and FVC. Effects of work exposure on lung function are similar to those found in other studies.

Adolescent↗
PubMed1981

Lipid composition of lung and lung lavage fluid from map turtles (Malaclemys geographica) maintained at different environmental temperatures.

The phospholipids of lung and lung lavage fluid from map turtles (Malaclemys geographica) acclimated to 5, 14, 22 and 32 degrees C have been analyzed. The yield of surfactant (lavage) lipid P was higher at 32 than at 5 degrees C, but there was no significant change in lung lipid P. The relative proportions of phospholipids from the lung were PC greater than PE greater than SM greater than PS greater than PI, while those for the lavage were PC greater than PI greater than PE greater than SM congruent to PS. PC constituted 71-78% of the surfactant phospholipid over the temperature range. Small changes in the amounts of PC and PE of lung and in PC and PI of lavage were observed at different temperatures. The fatty acid compositions of the lipids from the two sources were different in many respects. The lavage lipids contained more saturated acids, especially palmitic acid, than did the lung lipids. The fatty acid compositions indicated the presence of disaturated PC in lung lavage and diunsaturated species of PC and PE in lung. The total saturated fatty acids of PC and PE in lung and of PC in surfactant increased at higher temperatures. In the surfactant PC this increase reflected principally a rise in palmitate and a drop in palmitoleate contents. The saturated PC obtained from lavage at each temperature contained more than 85% palmitic acid, indicating that the principal saturated PC was DPPC. These changes are consistent with the type of alterations in the lipid composition of membranes which occur during homeoviscous adaptation.

Adaptation, Physiological↗
PubMed1981

Ventilation-perfusion lung scanning in patients detected by a screening program for early lung carcinoma.

Ventilation-perfusion (V-P) lung scans obtained in 114 patients in screening program for the early detection of lung cancer were reviewed, and abnormalities were correlated with radiographic and surgical findings. Eighty-seven patients eventually had a tissue diagnosis of carcinoma; 65 (75%) had a perfusion defect and 56 (67%) had a ventilation abnormality at the tumor site. Lobar or segmental perfusion abnormalities were present at the tumor site in two of 13 patients whose lung cancer could not be localized by chest radiographs. However, 12 of these 13 patients and 54% of those with radiographically visible lesions had perfusion abnormalities in other lung regions. Twenty-seven patients with suspected carcinoma who were subsequently proved to have benign lesions had V-P abnormalities similar to those in patients with lung cancer. Thus, no pattern of V-P abnormalities similar to those in patients with lung cancer. Thus, no pattern of V-P abnormalities allowed lung cancer in this screened population to be reliably distinguished from coexisting airway disease or non-malignant pulmonary masses. V-P lung studies have a limited role in the early detection of lung cancer.

Aged↗
PubMed1991

Cytokine signaling in lung: transforming growth factor-beta secretion by lung fibroblasts.

Control of growth and phenotypic expression of interstitial fibroblasts is a critical determinant of lung architecture and physiology during processes of growth and remodeling. We examined the ability of lung fibroblasts to produce transforming growth factor-beta (TGF-beta), a cytokine that is known to modulate proliferation and phenotypic expression of mesenchymal cells. Cultures of fibroblasts isolated from rat lungs spontaneously secrete TGF-beta as measured in the standard bioassay of anchorage-independent growth of normal rat kidney (NRK) cells in soft agar. Rat lung fibroblasts secrete TGF-beta in an inactive precursor form. Fibroblasts cultured from adult and fetal rat lungs produced comparable amounts of TGF-beta. The ability of lung fibroblast supernatant fluids to induce colony formation in soft agar could be completely neutralized by preincubation of samples with anti-TGF-beta immunoglobulin (Ig). Anti-platelet-derived growth factor IgG had no effect on anchorage-independent growth of NRK cells driven by rat fibroblast culture supernatant samples. These results indicate that TGF-beta does not require the presence of and interaction with secondary cytokines for its activity. In contrast to the results obtained with rat cells, neither human fetal nor adult lung fibroblasts secreted detectable amount of active TGF-beta or its inactive precursor. This was not due to the presence of TGF-beta inhibitors in fibroblast culture media, because the addition of purified porcine TGF-beta to conditioned medium from human lung fibroblast cultures yielded the expected increase in NRK cell growth in soft agar. These results point to differing cytokine control patterns in the lungs of the two species.

Animals↗
PubMed1996

In vivo mitogenic action of HGF on lung epithelial cells: pulmotrophic role in lung regeneration.

Hepatocyte growth factor (HGF) has mitogenic, morphogenic, and motogenic activities on epithelial cells and plays important roles in regeneration of the liver and the kidney. We previously found that the expression of HGF gene is rapidly induced in the lung after acute lung injury in experimental animals and that HGF levels are elevated in blood of patients with lung diseases. To search for a possible pulmotrophic function of HGF in lung regeneration, we examined the mitogenic activity of HGF on tracheal epithelial cells in vitro and evaluated the efficacy of HGF-administration on lung regeneration after acute lung injury in mice. HGF markedly stimulated proliferation and DNA synthesis of rat tracheal epithelial cells in primary culture in a dose-dependent manner. The intravenous injection of human recombinant HGF (10 micrograms.mouse-1.day-1) into mice with acute lung injury induced by the intratracheal infusion of 10 mM HCI stimulated DNA synthesis of airway epithelial cells to levels threefold higher than those in mice with no HGF-injections, but it did not stimulate DNA synthesis of alveolar epithelial cells. However, HGF injection at higher dose (100 micrograms.mouse-1.day-1) stimulated DNA synthesis of alveolar epithelial cells in vivo. These results indicate that HGF is a potent mitogen for airway epithelial cells and alveolar epithelial cells in vivo as well as in vitro. HGF may act as pulmotrophic factor responsible for airway and alveolar regeneration during lung regeneration after acute lung injury.

Animals↗
PubMed1998

Modulation of lung liquid clearance by isoproterenol in rat lungs.

beta-Adrenergic agonists have been reported to increase lung liquid clearance by stimulating active Na+ transport across the alveolar epithelium. We studied mechanisms by which beta-adrenergic isoproterenol (Iso) increases lung liquid clearance in isolated perfused fluid-filled rat lungs. Iso perfused through the pulmonary circulation at concentrations of 10(-4) to 10(-8) M increased lung liquid clearance compared with that of control lungs (P < 0.01). The increase in lung liquid clearance was inhibited by the beta-antagonist propranolol (10(-5) M), the Na(+)-channel blocker amiloride (10(-4) M), and the antagonist of Na-K-ATPase, ouabain (5 x 10(-4) M). Colchicine, which inhibits cell microtubular transport of ion-transporting proteins to the plasma membrane, blocked the stimulatory effects of Iso on active Na+ transport, whereas the isomer lumicolchicine, which does not affect cell microtubular transport, did not inhibit Na+ transport. In parallel with these changes, the Na-K-ATPase alpha 1-subunit protein abundance and activity increased in alveolar type II cells stimulated by 10(-6) M Iso. Colchicine blocked the stimulatory effect of Iso and the recruitment of Na-K-ATPase alpha 1-protein to the basolateral membrane of alveolar type II cells. Accordingly, Iso increased active Na+ transport and lung liquid clearance by stimulation of beta-adrenergic receptors and probably by upregulation of apical Na+ channels and basolateral Na-K-ATPase mechanisms. Recruitment from intracellular pools and microtubular transport of Na+ pumps to the plasma membrane participate in beta-adrenergic stimulation of lung liquid clearance in rat lungs.

Adrenergic beta-Agonists↗
PubMed1994

Regional lung hematocrit variation and assessment of acute lung injury.

Estimating blood content in the lung remains a key step in calculating lung water volume and microvascular permeability. We studied the effect of regional lung hematocrit (Hct) variation on assessment of acute lung injury. Escherichia coli endotoxin was administered in guinea pigs intravenously. Lung injury was evaluated by measuring the wet-to-dry weight ratio (W/D) and transvascular 125I-labeled albumin leakage for 3 h [tissue-to-plasma 125I-albumin ratio (T/P)] in five tissue samples from each animal. Residual blood content was corrected using either 51Cr-red blood cells as a blood cell marker, 99mTc-albumin as a plasma marker, or both, injected 10 min before the guinea pigs were killed. Lung Hct, estimated from the marker counts of lung and peripheral blood samples, was lower than peripheral blood Hct; intraindividual variation, represented by the standard deviation in each subject, was 0.024 +/- 0.015 for the control group (coefficient of variation 8.0 +/- 5.1%) and 0.026 +/- 0.013 for the endotoxin group (coefficient of variation 8.5 +/- 4.1%). Uncorrected W/D for residual blood content was greater than the corrected W/D. 99mTc-albumin correction gave values closer to the W/D corrected by both markers. T/P corrected by 99mTc-albumin showed smaller data variations than the values obtained with 51Cr-red blood cell correction, which was affected by variations in lung Hct. We recommend using a plasma marker to correct for blood content in assessing acute lung injury by W/D and T/P.

Animals↗
PubMed1997

When does the lung die? Kfc, cell viability, and adenine nucleotide changes in the circulation-arrested rat lung.

Lungs harvested from cadaveric circulation-arrested donors may increase the donor pool for lung transplantation. To determine the degree and time course of ischemia-reperfusion injury, we evaluated the effect of O2 ventilation on capillary permeability [capillary filtration coefficient (Kfc)], cell viability, and total adenine nucleotide (TAN) levels in in situ circulation-arrested rat lungs. Kfc increased with increasing postmortem ischemic time (r = 0.88). Lungs ventilated with O2 1 h postmortem had similar Kfc and wet-to-dry ratios as controls. Nonventilated lungs had threefold (P < 0.05) and sevenfold (P < 0.0001) increases in Kfc at 30 and 60 min postmortem compared with controls. Cell viability decreased in all groups except for 30-min postmortem O2-ventilated lungs. TAN levels decreased with increasing ischemic time, particularly in nonventilated lungs. Loss of adenine nucleotides correlated with increasing Kfc values (r = 0.76). This study indicates that lungs retrieved 1 h postmortem may have normal Kfc with preharvest O2 ventilation. The relationship between Kfc and TAN suggests that vascular permeability may be related to lung TAN levels.

Adenine Nucleotides↗
PubMed1998

Epidermal growth factor increases lung liquid clearance in rat lungs.

Epidermal growth factor (EGF) has been reported to stimulate the proliferation of epithelial cells and increase Na+ flux and Na+-K+-ATPase function in alveolar epithelial cell monolayers. Increases in Na+-K+-ATPase in alveolar type II cells (AT2) have been associated with increased active Na+ transport and lung edema clearance across the rat alveolar epithelium in a model of proliferative lung injury. Thus we tested whether administration of aerosolized EGF to rat lungs would increase active Na+ transport and lung liquid clearance. Sixteen adult Sprague-Dawley male rats were randomized to three groups. To a group of six rats, an aerosol generated from 20 microgram of EGF in saline was delivered to the lungs, to a second group of five rats only aerosolized saline was delivered, and a third group of five rats without treatment served as the control. Forty-eight hours postaerosolization of rat lungs with EGF there was an approximately 40% increase in active Na+ transport and lung liquid clearance compared with control rats, in the absence of changes in 22Na+, [3H]mannitol, and albumin permeabilities. The Na+-K+-ATPase activity in AT2 cells harvested from these lungs was increased in rats that received aerosolized EGF compared with AT2 cells from both control rats and rats receiving aerosolized saline. These results support the hypothesis that in vivo delivery of EGF aerosols upregulates alveolar epithelial Na+-K+-ATPase and increases lung liquid clearance in rats.

Animals↗
PubMed2005

Time course of lung parenchyma remodeling in pulmonary and extrapulmonary acute lung injury.

The aim of this study is to test the hypothesis that the early changes in lung mechanics and the amount of type III collagen fiber do not predict the evolution of lung parenchyma remodeling in pulmonary and extrapulmonary acute lung injury (ALI). For this purpose, we analyzed the time course of lung parenchyma remodeling in murine models of pulmonary and extrapulmonary ALI with similar degrees of mechanical compromise at the early phase of ALI. Lung histology (light and electron microscopy), the amount of elastic and collagen fibers in the alveolar septa, the expression of matrix metalloproteinase-9, and mechanical parameters (lung-resistive and viscoelastic pressures, and static elastance) were analyzed 24 h, 1, 3, and 8 wk after the induction of lung injury. In control (C) pulmonary (p) and extrapulmonary (exp) groups, saline was intratracheally (it; 0.05 ml) instilled and intraperitoneally (ip; 0.5 ml) injected, respectively. In ALIp and ALIexp groups, mice received Escherichia coli lipopolysaccharide (10 microg it and 125 microg ip, respectively). At 24 h, all mechanical and morphometrical parameters, as well as type III collagen fiber content, increased similarly in ALIp and ALIexp groups. In ALIexp, all mechanical and histological data returned to control values at 1 wk. However, in ALIp, static elastance returned to control values at 3 wk, whereas resistive and viscoelastic pressures, as well as type III collagen fibers and elastin, remained elevated until week 8. ALIp showed higher expression of matrix metalloproteinase-9 than ALIexp. In conclusion, insult in pulmonary epithelium yielded fibroelastogenesis, whereas mice with ALI induced by endothelial lesion developed only fibrosis that was repaired early in the course of lung injury. Furthermore, early functional and morphological changes did not predict lung parenchyma remodeling.

Adaptation, Physiological↗
PubMed2006

Influence of inflated lung pressure on lung mechanical properties during cold storage in rats.

The degree of lung inflation pressure during cold storage has a deep connection with lung functions after reperfusion. However, the change of the lung mechanical properties during cold storage at the different lung inflation pressure is unknown. We investigated the change of the mechanical properties both at the organ and the tissue level under different inflated lung pressure soon after the cold storage. In group I, the lungs were not preserved. In group II, the lungs were preserved in deflated condition. In groups III and IV, the lungs were inflated with room air at pressures of 14 and 25 cm H2O. After 24-hour storage, the input impedance (Z) was measured by a computer-controlled small animal ventilator (n = 8 each group). All data were analyzed using a homogeneous linear model, which includes airway resistance (R(aw)), tissue elastance (H), and tissue damping (G). Hysteresivity (eta) was calculated as G/H. After Z measurement, the tissue elasticity (Eqs) obtained from the quasi-static stress-strain curve was compared. We also analyzed the biochemical changes of surfactant in bronchoalveolar lavage (BAL) fluid. R(aw )was significantly lower in groups III and IV than in group I (p < 0.01). Hysteresivity (eta) was significantly lower in group IV than in groups I and III (p < 0.05). Eqs was significantly higher in groups III and IV than in groups I and II (p < 0.01). The total protein level in the BAL fluid of the preserved groups was significantly higher compared with group I (p < 0.01). We conclude that hyperinflated storage would deteriorate lung tissue mechanical properties.

Acclimatization↗