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Pathologic comparison of video-assisted thoracic surgical lung biopsy with traditional open lung biopsy.

Video-assisted thoracic surgical lung biopsy is an alternative to traditional open lung biopsy for diagnosis in patients with pleuropulmonary diseases. Between January 7, 1991, and August 3, 1993, 71 consecutive patients had video-assisted thoracic surgical lung biopsy and 42 patients had traditional open lung biopsy. A specific histologic diagnosis that correlated with the clinical findings was sought in each case and the yield was compared between the two groups. Procedure-related artifactual changes were also evaluated; the extent of traumatic hemorrhage and neutrophil margination as a result of tissue manipulation was significantly greater for patients in the video-assisted thoracic surgical lung biopsy group than for those in the open lung biopsy group, but the changes were generally minor and did not affect diagnostic yield. Complications developed in 11 (15%) of 71 patients in the video-assisted thoracic surgical lung biopsy group including 5 patients with prolonged air leakage (more than 10 days); 2 with pneumonia; and 1 each with bleeding, late pneumothorax necessitating readmission, mucus plug necessitating bronchoscopy, and a hypoxic episode necessitating mechanical ventilation. On the other hand, 7 (17%) of 42 patients in the open lung biopsy group had complications including 4 patients with prolonged air leakage (more than 10 days) and 3 with pneumonia. There were 6 (8%) operative deaths in patients who had video-assisted thoracic surgical lung biopsy and 7 (17%) in the open lung biopsy group; all had preoperative respiratory failure. We conclude that video-assisted thoracic surgical lung biopsy is an acceptable alternative to open lung biopsy for diagnosis of pulmonary infiltrates or indeterminate nodules.

Adult↗

Lasting beneficial effect of short-term inhaled nitric oxide on graft function after lung transplantation. Paris-Sud University Lung Transplantation Group.

The combination of ischemia and reperfusion after lung transplantation is characterized by endothelial damage, neutrophil sequestration, and decreased release of endothelial nitric oxide. Because nitric oxide has been shown to selectively dilate the pulmonary vasculature, abrogate neutrophil adherence, and restore endothelial dysfunction, we hypothesized that inhaled nitric oxide given for 4 hours during initial reperfusion might attenuate reperfusion injury in a porcine model of left single-lung transplantation. We tested hemodynamic and gas exchange data, lung neutrophil sequestration, and pulmonary artery endothelial dysfunction after 4 and 24 hours of reperfusion in 12 pigs randomly assigned to nitric oxide and control groups. Harvested lungs were preserved in normal saline solution for 24 hours at 4 degrees C. During transplantation, inflatable cuffs were placed around each pulmonary artery to allow separate evaluation of each lung by occluding flow. Compared with the transplanted lungs in the control group, transplanted lungs in pigs treated with inhaled nitric oxide significantly improved gas exchange, pulmonary vascular resistance, shunt fraction, and oxygen delivery at 4 and 24 hours after reperfusion. Neutrophil sequestration, as measured by the neutrophil-specific enzyme myeloperoxidase and the alveolar leukocyte count per light microscopic field, was significantly lower at 24 hours after reperfusion in the transplanted lungs of the nitric oxide group. The nitric oxide-treated native right lungs exhibited significantly reduced increase in neutrophil accumulation compared with that in control native right lungs. After 24 hours of reperfusion, endothelium-dependent relaxation to acetylcholine was similarly and severely altered in both groups. We conclude that short-term inhaled nitric oxide given during the first 4 hours of reperfusion after lung transplantation significantly attenuates reperfusion injury, improving graft function as long as 24 hours after operation. This effect is probably mediated by a decrease in neutrophil sequestration. A protective effect on the contralateral lung was also observed. Inhaled nitric oxide may be a suitable agent when an acute reperfusion phenomenon is anticipated.

Administration, Inhalation↗

Lung retrieval from non-heart beating cadavers with the use of a rat lung transplant model.

BACKGROUND: Lungs retrieved from cadavers after death and circulatory arrest may alleviate the critical shortage of lungs for transplant. We report a rat lung transplantation model that allows serial measurement of arterial blood gases after left single lung transplantation from non-heart beating donors. METHODS: Twelve Sprague-Dawley rats underwent left lung transplantation with a vascular cuff technique. Donor rats were anesthetized with intraperitoneal injection of pentobarbital, heparinized, intubated via tracheotomy, and then killed with pentobarbital. Lungs were retrieved immediately or after 2 hours of oxygen ventilation after death (tidal volume 1 mL/100 g, rate 40/min FIO2 = 1.0, positive end-expiratory pressure 5 cm H2O). Recipient rats were anesthetized, intubated, and ventilated. The carotid artery and jugular vein were cannulated for arterial blood gases and infusion of Ringer's lactate (4 mL/h). Anesthesia was maintained with halothane 0.2%, and recipient arterial blood gases were measured at 4 and 6 hours after lung transplantation after snaring the right pulmonary artery for 5 minutes. Animals were put to death 6 hours after lung transplantation, and portions of transplanted lungs were frozen in liquid nitrogen and assayed for wet/dry ratio, myeloperoxidase as a measure of neutrophil infiltration, and conjugated dienes as a measure of free radical-mediated lipid peroxidation. RESULTS: Arterial PO2 and wet/dry ratio were not significantly different in recipients of non-heart beating donor lungs retrieved immediately after death or after 2 hours of oxygen ventilation. Significant neutrophil infiltration was observed in recipients of non-heart beating donor lungs retrieved 2 hours after death from oxygen-ventilated donors. CONCLUSIONS: Strategies to ameliorate reperfusion injury may allow for successful lung transplantation from non-heart beating donors.

Animals↗

DNA adducts in tumour, normal peripheral lung and bronchus, and peripheral blood lymphocytes from smoking and non-smoking lung cancer patients: correlations between tissues and detection by 32P-postlabelling and immunoassay.

Smoking is a major risk factor for lung cancer. This comparative study of smoking-related carcinogen-DNA adducts in pulmonary tissues and peripheral blood lymphocytes aims to further explore the primary DNA damaging processes by cigarette smoke in target and surrogate tissues. Samples of tumour and normal peripheral lung tissue, normal bronchial tissue and peripheral blood lymphocytes were obtained from a total of 85 lung cancer patients who underwent lung resection. Bulky DNA adducts were determined by 32P-postlabelling, and polycyclic aromatic hydrocarbon (PAH)-DNA adducts were detected by (+/-)-7beta, 8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-DNA chemiluminescence immunoassay (BPDE-DNA CIA) in smaller subsets of tissue samples subject to availability of DNA. Bulky DNA adduct levels ranged between 0.3 and 27.8 adducts/10(8) nucleotides (nt) with mean adduct levels between 2.8 and 11.5 adducts/10(8) nt. Mean PAH-DNA adduct levels were 2.6-6.2 adducts/10(8) nt. Significantly higher bulky DNA adduct levels were detected in smokers' lungs as compared with non-smokers' (P < 0.02). PAH-DNA adduct levels appeared higher in the lungs of smokers compared with non-smokers but the difference was not significant. Lung tumour contained on average a 50% lower DNA adduct level compared with normal lung tissue. A statistically significant positive correlation was found between the DNA adduct levels of the corresponding tumour and normal lung tissue samples in both smokers and non-smokers using both methodologies. Bulky DNA adduct levels in normal lung and blood lymphocytes correlated significantly in non-smokers only (r = 0.55, P = 0.023). In lung tumour DNA samples there was a weak correlation between values obtained by 32P-postlabelling and by the BPDE-DNA immunoassay (r = 0.27, P = 0.054). However, with normal lung DNA samples, values obtained by the two assays did not correlate.

Adult↗

Lung perfusion demonstrated by contrast-enhanced dynamic magnetic resonance imaging. Application to unilateral lung transplantation.

RATIONALE AND OBJECTIVES: The authors evaluate the use of magnetic resonance (MR) to image pulmonary perfusion in healthy controls and to detect pulmonary defects in patients with unilateral lung transplantation, using dynamic images after contrast administration. METHODS: Five patients with right lung transplantation and nine healthy volunteers underwent MR imaging. Twenty-five subsecond contrast-enhanced MR images (turbo-fast low-angle shot [FLASH]) were obtained at the level of the pulmonary arteries after a single injection of gadopentetate dimeglumine (0.1 mmol/kg) in an antecubital vein. Perfusion lung scintigraphy was done within 24 hours after the MR imaging examination in the transplanted patients. RESULTS: Before administration of contrast material, MR images showed both lungs to be homogeneous and of low signal intensity in healthy controls and in patients with lung transplantation. After contrast administration in controls, the mean signal intensity of the dependent lung increased markedly to 171 +/- 24% above baseline, whereas the nondependent signal intensity lung increased by only 105 +/- 17%; these changes were significantly different. In all patients with lung transplantation, a clear perfusion defect was demonstrated in the native lung. This defect was confirmed in all cases by perfusion nuclear scintigraphy, which showed that the majority of lung perfusion is directed to the transplanted allograft, compared with the native contralateral lung. CONCLUSIONS: Our results suggest that dynamic contrast-enhanced MR imaging is a potential method for detecting pulmonary perfusion defects in patients with lung transplantation.

Adult↗

Extravascular lung water determined with single transpulmonary thermodilution correlates with the severity of sepsis-induced acute lung injury.

OBJECTIVE: To find out if the extravascular lung water index (EVLWI) and the derived permeability indexes determined by the single transpulmonary thermodilution technique are associated with markers of acute lung injury in human septic shock. DESIGN: Prospective, observational study. SETTING: Mixed intensive care unit of a 900-bed university hospital. PATIENTS: Thirty-eight consecutive adult patients with septic shock and acute lung injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The variables were assessed over a 72-hr period and included hemodynamics, EVLWI, and pulmonary vascular permeability indexes determined with the single indicator transpulmonary thermodilution technique, lung compliance, oxygenation ratio (Pao2/Fio2), lung injury score, cell counts, and the plasma concentration of endothelin-1. At day 1, EVLWI was elevated (>or=7 mL/kg) in 28 (74%) patients and correlated with lung compliance (r=-.48, p=.002), Pao2/Fio2 (r=-.50, p=.001), lung injury score (r=.46, p=.004), roentgenogram quadrants (r=.39, p=.02), and platelet count (r=-.43, p=.007). At day 3, EVLWI correlated with compliance (r=-.51, p=.002), Pao2/Fio2 (r=-.49, p = .006), and lung injury score (r=.53, p=.003). At day 3, EVLWI and pulmonary vascular permeability indexes were higher in nonsurvivors (p<.05). The plasma concentration of endothelin-1 (mean+/-sd) was significantly higher in patients with elevated EVLWI (>or=7 mL/kg) (3.85+/-1.40 vs. 2.07+/-0.38 pg/mL, respectively). Twenty-two (59%) patients died before day 28. CONCLUSIONS: In human septic shock, EVLWI demonstrated moderate correlation with markers of acute lung injury, such as lung compliance, oxygenation ratio, roentgenogram quadrants, and lung injury score. In nonsurvivors, EVLWI and permeability indexes were significantly increased at day 3. Thus, EVLWI might be of value as an indicator of prognosis and severity of sepsis-induced acute lung injury.

Biomarkers↗

Lung volumes after an increase in lung distension in pneumonectomized ferrets.

To investigate the role of lung distension in compensatory lung growth, the right lung of each of 21 adult male ferrets was replaced with a silicone rubber balloon filled with mineral oil. Three to thirteen weeks after surgery, the oil was removed through a subcutaneous port. Lung volumes were measured serially until 3-6 wk after balloon deflation. With pneumonectomy the total lung capacity (TLC) decreased to less than 50% of the preoperative value and remained essentially unchanged while the balloon was inflated. At balloon deflation, TLC and vital capacity did not change immediately, whereas functional residual capacity increased by 44%, indicating a change of 2-3 cmH2O in end-expiratory transpulmonary pressure. TLC increased by 10% within 3 days and continued to increase over the subsequent 3-5 wk by a total of 25% over TLC at balloon deflation. There was little difference in this response between animals whose balloons were deflated 3 wk after surgery and those in which deflation was delayed up to 13 wk. After pneumonectomy in the adult ferret, the remaining lung increases in volume in response to an increase in lung distension even weeks or months after surgery. The extent to which this volume increase involves lung tissue growth or depends on previous lung resection is at present unknown. This model may be useful for studies of the mechanisms by which lung distension influences lung volume and compensatory lung growth.

Animals↗

The development of the newborn rat lung in hyperoxia: a dose-response study of lung growth, maturation, and changes in antioxidant enzyme activities.

To examine the dose-response relationships of oxygen-induced lung changes, newborn rats were exposed to various patterns of concentrations of hyperoxia (0.4, 0.8, and greater than 0.95 FiO2) for up to 12 days. Prominent findings included microscopic evidence of lung injury and retarded alveolar development (secondary septal development delayed by as much as 88%), lower whole lung DNA (50% of control), lung-to-body-weight ratios (by as much as 18%), and significantly less compliance in the lungs afer exposures of 6 or 12 day duration to all concentrations of hyperoxia. Significant increases in the activities of the lung protective enzymes superoxide dismutase (129 to 160% of control), catalase (112 to 274% of control), and glutathione peroxidase (118 to 256% of control) were noted when activity was expressed on a DNA basis after 12 day exposures to the various patterns of hyperoxia. Lung changes noted after a 7-day recovery period in air included interstitial thickening (117% of control), persistance of the microscopic injury, and retarded alveolar development seen immediately after initial 6-day hyperoxic exposures. At the conclusion of a second wk of recovery in air, the lungs of hyperoxic exposed animals resembled controls in most respects, but a significantly altered compliance was exhibited by the lungs of animals initially exposed to 6 days of 0.4 or greater than 0.95 FiO2. The dose dependency of oxygen-induced lung injury is complex. Straightforward, stepwise dose-response adequately describes the evolution of microscopic injury and slowing of alveolar development in hyperoxia, but the dose dependency is not as clearly identified in the oxygen-induced retardation of lung growth including DNA content and in changes in antioxidant enzyme activities. Changes in lung compliance clearly do not follow expected dose response relationships.

Animals↗

Pulmonary nitric oxide synthases and nitrotyrosine: findings during lung development and in chronic lung disease of prematurity.

BACKGROUND: Nitric oxide mediates and modulates pulmonary transition from fetal to postnatal life. NO is synthesized by 3 nitric oxide synthase isoforms. One key pathway of nitric oxide metabolism results in nitrotyrosine, a stable, measurable marker of nitric oxide production. OBJECTIVE: The purpose of this study was to assess, by semiquantitative immunohistochemistry, nitric oxide synthase isoforms and nitrotyrosine at different airway and vascular tree levels in the lungs of neonates at different gestational ages and to compare results in control groups to those in infants with chronic lung disease. DESIGN/METHODS: Formalin-fixed, paraffin-embedded, postmortem lung blocks were prepared for immunohistochemistry using antibodies to each nitric oxide synthase isoform and to nitrotyrosine. Blinded observers evaluated the airway and vascular trees for staining intensity (0-3 scale) at 5 levels and 3 levels, respectively. The control population consisted of infants from 22 to 42 weeks' gestation who died in < 48 hours. Results were compared with gestation-matched infants with varying severity of chronic lung disease. RESULTS: In control and chronic lung disease groups, 22 to 42 weeks' gestation, staining for all 3 of the nitric oxide synthase isoforms was found in the airway epithelium from the bronchus to the alveolus or distal-most airspace. The abundance or distribution of nitric oxide synthase-3 staining in the airways did not show significant correlation with gestational age or severity of chronic lung disease. In the vascular tree, intense nitric oxide synthase-3 and moderate nitric oxide synthase-2 staining was found; nitric oxide synthase-1 was not consistently stained. Nitrotyrosine did stain in the pulmonary tree. Compared with controls where nitrotyrosine staining was minimal, regardless of gestation, in infants with chronic lung disease there was more than fourfold increase between severe chronic lung disease (n = 12) and either mild chronic lung disease or control infants (n = 16). CONCLUSIONS: All 3 of the nitric oxide synthase isoforms and nitrotyrosine are detectable by immunohistochemistry early in lung development. Nitric oxide synthase ontogeny shows no significant changes in abundance or distribution with advancing gestational age nor with chronic lung disease. Nitrotyrosine is significantly increased in severe chronic lung disease.

Age Factors↗

Wet-to-dry ratio of lung tissue and surfactant outwash after one-lung flooding.

Unilateral flooding of the lung after intubation with a double-lumen tube enables intraoperative sonography of the lung tissue. The flooding restricts the pulmonary blood stream of the flooded lung in a relevant degree and thus reduces the right-to-left shunt volume. The deficient perfusion of the lung tissue during the flooded phase might cause capillary permeability disorders and secondary oedema development. This can be determined by examination of extravascular lung water (EVLW) after draining and reventilation of the flooded lung. Although one-time unilateral lung flooding must be distinguished from bronchopulmonary lavage, it is interesting to study the effects of flooding on the surfactant system. The wet-to-dry ratio of the lung tissues of 13 female pigs was ascertained at different times following one-lung flooding (1 to 11 weeks). A trend towards an increased wet-to-dry ratio in the previously flooded lung was found only in the tissue samples taken 1 h after reventilation. After only 24 h, the two lungs no longer differed in their wet-to-dry ratio. In six pigs, the phospholipid content of the drained flooding liquid was determined. It was shown that the surfactant loss caused by flooding was maximally 47% of the calculated surfactant pool of the respective lung.

Animals↗

Detection of lung rejection with indium-111-labeled lymphocytes in heterotopic rat heart-lung transplantation.

To determine if acute lung rejection after heart-lung transplantation can be detected noninvasively with indium-111-labeled (111In) lymphocytes, we studied 33 allogeneic and 18 isogeneic heterotopic heart-lung transplants in rats. Twenty-four hours after injection of isogeneic splenic 111In-lymphocytes (75 +/- 2 microCi/100 million cells), animals were scanned at 2 to 8 days after transplant (Tx). Also, percent indium uptake of the graft was determined and compared with pathologic lung changes. Between the vascular and destructive phases of lung rejection, 111In-lymphocyte uptake of lung allografts was significantly greater than isografts (p less than 0.001). Lung allografts in the alveolar phase (4-6 days after Tx) showed the most intense uptake (2.7 +/- 0.1%) of injected 111In-lymphocytes. All scintigrams of allografts from the late vascular to the early destructive phase (3-7 days after Tx) showed visualization of the lung graft (27/27 true positive, sensitivity = 100%). In contrast, lung isografts of the same period showed no pathological sign of rejection and were only rarely visualized (12/14 true negative, specificity = 86%). Lung rejection may be accurately assessed noninvasively by gamma scintigraphy with 111In-lymphocytes. This technique may prove useful in the detection of acute lung rejection in human heart-lung transplant recipients. Modification of the labeling dose chosen may further improve scan accuracy.

Abdomen↗

Stage-specific expression of SSEA-1-related antigens in the developing lung of human embryos and its relation to the distribution of these antigens in lung cancers.

The localization of three carbohydrate antigens, Lex, Ley, and sialylated Lex-i, which are closely related to stage-specific embryonic antigen 1, in the lung of developing human embryos was investigated using specific monoclonal antibodies. In the 38-day-old embryo, when the primitive lung bud has appeared and developed into two lung sacs, only Ley antigen was specifically positive in the proliferating cells in the terminal portion of lung bud. In the 50-53-day-old embryos, the future bronchi were actively developing from the bronchial buds. At this stage, the Ley antigen was maximally expressed and the Lex antigen appeared in the bud cells. In the lung of the 12-week-old embryo, buds for the future bronchioles were lined by simple cuboidal epithelial cells, which were strongly positive for Lex antigen, weakly positive for Ley antigen, and still completely negative for sialylated Lex-i antigen. Sialylated Lex-i antigen finally appeared in 18-week-old embryos, in the cells of the terminal buds for the future alveoli. At this stage, the Lex and Ley antigens were already beginning to disappear and were only weakly positive in cells of terminal buds. At 20 weeks, only sialylated Lex-i antigen was weakly detected in the cells in the terminal buds; after 8 months, all three antigens were essentially not detected in the respiratory cells in most of the embryos examined in this study. Formation of bronchial glands was detected at 18 weeks, where the developing gland cells were specifically positive for sialylated Lex-i antigen. Ciliation of the bronchial epithelial cells started at 12 weeks and propagated thereafter. The ciliation was accompanied by the reappearance of Ley and Lex antigen in the epithelial cells. These findings collectively indicated that the three antigens all have a physiological significance as stage-specific developmental antigens of the human lung; those antigens were specifically present in the bud cells at each important step of the morphogenesis of the human lung, such as cells in the lung buds, bronchial buds, and terminal buds for the formation of the alveolus, and cells differentiating into bronchial gland cells. The three antigens gradually disappear in the later stage of development along with the maturation process of the lung. Stage-specific embryonic antigen 1 and related antigens are known to be associated with various human cancers, including lung cancers. We suggest that the expression of these antigens in the lung cancer cells is the result of the retrodifferentiation of the cancer cells to the stages of immature embryonic lung cells.

Adenocarcinoma↗

Production and molecular size heterogeneity of immunoreactive gastrin-releasing peptide in fetal and adult lungs and primary lung tumors.

Gastrin-releasing peptide (GRP) is known to be a bombesin-like peptide present in mammalian tissues. Using GRP radioimmunoassay specific for carboxyl-terminal portion, the immunoreactive GRP (IR-GRP) content of 5 fetal lungs, 38 adult lungs, and 131 primary lung tumors was determined. All fetal lung extracts contained IR-GRP ranging from 31 to 140 ng/g, wet weight. IR-GRP was present in 7 to 21% of normal adult lungs and lung carcinomas other than small-cell carcinoma; the amount was not very large except in two cases of adenocarcinoma, in which 110 and 140 ng/g of IR-GRP were detected. In the case of small-cell carcinoma, IR-GRP was found in 23 of the 31 cases examined (74%), and nine (29%) of these contained large amounts of IR-GRP (100 to 14,000 ng/g). As for carcinoid tumors, IR-GRP was found in five of the 12 cases examined (42%), and large amounts of IR-GRP were detected in two cases (5,100 to 130,000 ng/g). Immunohistochemically, IR-GRP was found in the neuroendocrine cells of fetal lungs and in the tumor cells of primary lung tumors. When these tissue extracts were examined by bombesin radioimmunoassay that recognizes bombesin but not GRP, they did not contain immunoreactive bombesin, suggesting that IR-GRP in these tissues is more similar to GRP than to bombesin. Sephadex G-50 gel filtration always revealed two peaks of IR-GRP in both fetal lungs and IR-GRP-producing tumors. One was eluted at the position corresponding to that of porcine GRP (Peak 1) and the other, at the position just behind that of porcine GRP (14-27) (Peak 2). In the five fetal lungs, Peak 2 comprised more than 83% of the total IR-GRP. In the 12 IR-GRP-producing tumors examined, the ratio of these two peaks differed from case to case. Our data indicate that IR-GRP, which is present in fetal lung, is often produced by primary lung tumors, especially by small-cell carcinoma and carcinoid tumor, with molecular size heterogeneity.

Amino Acid Sequence↗

Evaluation of lung metabolism during successful twenty-four-hour canine lung preservation.

We used a canine left lung allotransplantation model to evaluate 24-hour lung preservation with two different electrolyte solutions, low-potassium dextran and low-potassium dextran with 1% glucose. To investigate changes in the energy status during preservation, we analyzed the lungs for adenosine triphosphate, phosphocreatine, and several metabolites of the glycolysis pathway and the citric acid cycle: glucose, glucose-6-phosphate, lactate, citrate, and malate. We also devised and evaluated a pulmonary cooling jacket to prevent rewarming of the lung during implantation. The lungs were divided into four groups. Groups I (n = 10) and II (n = 6) were flushed with low-potassium dextran and groups III (n = 6) and IV (n = 6) were flushed with low-potassium dextran solution with 1% glucose. The cooling jacket was used for groups II and IV only. After 24-hour preservation at 10 degrees C, the left lungs were implanted into the recipient animals. Function of the transplanted left lung was assessed during temporary (10 minutes) occlusion of the contralateral pulmonary artery while both lungs were ventilated with 100% oxygen. This assessment was performed at 1 hour and at 3, 8, and 22 days after transplantation. Immediately after transplantation the arterial oxygen tension was 279 +/- 70 mm Hg in group I, 376 +/- 56 mm Hg in group II, 523 +/- 41 mm Hg in group III, and 518 +/- 50 mm Hg in group IV. The arterial oxygen tension in groups III and IV were significantly greater than in group I (p < 0.05). Of the lungs preserved with low-potassium dextran solution with 1% glucose solution, 11 of 12 (92%) showed excellent lung function (arterial oxygen tension > 300 mm Hg) at 3 days; only 10 of 16 lungs preserved with low-potassium dextran achieved this level of function. Glucose, glucose-6-phosphate, lactate, citrate and malate levels decreased significantly during 24-hour preservation with low-potassium dextran solution; they were stable with low-potassium dextran solution with 1% glucose. Adenosine triphosphate and phosphocreatine were stable for 24 hours with both low-potassium dextran and low-potassium dextran solution with 1% glucose. The cooling jacket provided uniform cooling of the lung parenchyma during implantation, and significant increase in temperature was observed in its absence, with topical cooling by cold saline solution.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

Model predictions of the recruitment of lung units and the lung surface area-volume relationship during inflation.

Experimental evidence suggests that the lung behaves as if it is composed of a large population of units which are recruited and derecruited during lung expansion and contraction. This study combines two previous models in order to estimate the probability distribution function describing lung unit opening pressures and the resulting alveolar surface area-volume relationship of the excised rat lung during inflation. Results indicate that the opening pressures of lung units during inflation can be described by a normal distribution. The end-expiratory pressure (EEP) has a large effect on the number of lung units that open during inflation and the properties of the area-volume relationship of the lung, but the distribution of opening pressures of individual lung units is fairly consistent regardless of EEP. This study also presents evidence that when the normalized lung area-volume relationship is represented by the equation [A(L)]N = [phiV(L)]N(n) during inflation from the closed state, the expansion coefficient n is between 0.86 and 1. This result supports the theory that, for inflation from EEPs below 4 cmH2O, lung expansion occurs in part by the recruitment of lung units and not solely by the expansion of open units.

Adaptation, Physiological↗

Pre mortem analysis of lung injury and lung function in oxygen toxic rabbits.

OBJECTIVES: To determine whether respiratory system mechanics measurements could detect lung injury in oxygen toxic rabbits before clinical deterioration. To determine whether respiratory system mechanics measurements, using a power analysis, have the statistical power to detect significant reductions in hyperoxic lung injury due to an intervention when compared with traditional post mortem measurements of lung injury, extravascular lung water, and bronchoalveolar lavage protein concentration. DESIGN: Prospective, controlled study. SETTING: Institutional animal laboratories. SUBJECTS: Adult New Zealand white rabbits. INTERVENTIONS: Spontaneously breathing adult New Zealand white rabbits were exposed continuously to either > 95% oxygen or room air. MEASUREMENTS AND MAIN RESULTS: We measured arterial pH, blood gas tensions, and respiratory system mechanics in rabbits twice, both before exposure to > 95% oxygen, and after the rabbits developed symptoms of mild lung dysfunction. After the second set of respiratory system mechanics measurements, we measured extravascular lung water and bronchoalveolar lavage protein concentration in the hyperoxia-exposed rabbits and compared the values with those values obtained in animals that breathed room air only. Our hyperoxia-exposed rabbits developed symptoms of mild respiratory impairment at 69 +/- 2 hrs. In these hyperoxia-exposed rabbits, measurements of static compliance, quasi-static compliance and resistance all changed significantly (p < .05) when compared with baseline measurements. Functional residual capacity and arterial blood gas values did not change significantly. Furthermore, assuming that an intervention reduced hyperoxic lung injury by a given amount, we performed a power analysis and found that the measurement of static compliance had at least equivalent power to detect a reduction in lung injury from an intervention when compared with measurement of extravascular lung water and bronchoalveolar lavage protein concentration. CONCLUSIONS: Measurements of respiratory system mechanics can detect lung injury in hyperoxic rabbits before the onset of severe clinical deterioration or death. Furthermore, measurement of static compliance of the respiratory system is likely to be a powerful tool to detect a reduction in lung injury produced by an intervention.

Airway Resistance↗

Static lung-lung interactions in unilateral emphysema.

Motivated by the introduction of single-lung transplantation into clinical practice, we compared the static mechanical properties of the respiratory system in six supine dogs before (at baseline) with those after the induction of unilateral emphysema. Relaxation volume (Vrel), total lung capacity (TLC), and static compliance of the emphysematous lung increased to 214 +/- 68, 186 +/- 39, and 253 +/- 95% (SD) of baseline, respectively. Vrel of the nonemphysematous lung fell to 81 +/- 28% of baseline, with no significant change in TLC of the nonemphysematous lung or its pressure-volume relationship, indicating that unilateral hyperinflation does not cause dropout of contralateral lung units. After unilateral emphysema, the chest wall shifted to a higher unstressed or neutral volume (when pleural pressure equals atmospheric pressure) in three of six animals, minimizing the anticipated decrease in lung recoil pressure at the higher respiratory system Vrel. The pattern of relative lung emptying in the intact dog and in the excised lungs was similar during stepwise deflations from TLC, suggesting that mean pleural pressure of the hemithoraces is equal. We conclude that in the dog the static volume distribution between emphysematous and nonemphysematous lungs is determined only by differences in lung recoil and compliance.

Animals↗

Superoxide dismutases in the lung and human lung diseases.

The lungs are directly exposed to higher oxygen concentrations than most other tissues. Increased oxidative stress is a significant part of the pathogenesis of obstructive lung diseases such as asthma and chronic obstructive pulmonary disease, parenchymal lung diseases (e.g., idiopathic pulmonary fibrosis and lung granulomatous diseases), and lung malignancies. Lung tissue is protected against these oxidants by a variety of antioxidant mechanisms among which the superoxide dismutases (SODs) are the only ones converting superoxide radicals to hydrogen peroxide. There are three SODs: cytosolic copper-zinc, mitochondrial manganese, and extracellular SODs. These enzymes have specific distributions and functions. Their importance in protecting lung tissue has been confirmed in transgenic and knockout animal studies. Relatively few studies have been conducted on these enzymes in the normal human lung or in human lung diseases. Most human studies suggest that there is induction of manganese SOD and, possibly, extracellular SOD during inflammatory, but not fibrotic, phases of parenchymal lung diseases and that both copper-zinc SOD and manganese SOD may be downregulated in asthmatic airways. Many previous antioxidant therapies have been disappointing, but newly characterized SOD mimetics are being shown to protect against oxidant-related lung disorders in animal models.

Animals↗