Decreased pulmonary distensibility and pulmonary barotrauma in divers.

Pulmonary distensibility, lung volume and conductance were measured in 14 men (mean age 22 (SD 3) years) who suffered pulmonary barotrauma (PBT) during shallow water diving. Exponential analysis of static pressure-volume date obtained during deflation of the lungs gave K, and index of distensibility. The pulmonary conductance-recoil pressure (GL-PL) relationship was also obtained during deflation. Total lung capacity (TLC) was measured in a body plethysmograph or by nitrogen washout. The results were compared with 34 male nonsmokers and 10 healthy male divers. Mean lung volumes and FEV1 did not differ significantly in the three groups. In the PBT group K was decreased and recoil pressure was increased; the slope of the regression of GL and PL was decreased indicating stiffer airways. Decreased K reflects a decreased airspace size. Smaller airspaces increase the surface component of recoil pressure which increases the stress in tissue fibres. Relatively stiff airways may magnify the elastic stresses in peribronchial alveolar tissue increasing the possibility of rupture of alveolar walls with interstitial gas dissection.     

Are pulmonary bleb and bullae a contraindication for hyperbaric oxygen treatment?

BACKGROUND: Air cysts or blebs in the lungs may predispose pulmonary barotrauma (PBT) by causing air trapping when there is a change in environmental pressure. The changes in the environmental pressure are also seen during hyperbaric oxygen treatments (HBOT). AIM: The aim of this study was to determine how patients were evaluated for pulmonary blebs or bullae, and PBT prevalence in different HBOT centers. METHODS: HBOT centers were asked to participate in this study and a questionnaire was send via e-mail. A total of 98 centers responded to our questionnaire. RESULTS: Sixty-five HBOT centers (66.3%) reported that they applied HBOT to the patients with air cysts in their lungs. X-ray was the most widely used screening method for patients with a history of a lung disease. The prevalence of PBT in theses centers was calculated as 0.00045%. CONCLUSIONS: Our survey demonstrated that (1) a significant portion of the HBO centers accept patients with pulmonary bleb or bullae, (2) although insufficient, X-ray is the mostly used screening tool for patients with a history of pulmonary disease and (3) the prevalence of pulmonary barotrauma is very low in HBOT.     

Hemoptysis provoked by voluntary diaphragmatic contractions in breath-hold divers.

Pulmonary barotrauma of descent (lung squeeze) has been described in breath-hold divers when the lung volume becomes smaller than the residual volume (RV), with the effect of increased ambient pressure. However, the ratio between the total lung capacity and the RV is not the only factor that plays a role in the lung squeeze. Blood shift into the thorax is another important factor. We report three cases of hemoptysis in breath-hold divers who dove for spear fishing in shallower depths than usual. All of the divers performed voluntary diaphragmatic contractions at the beginning of their ascent, while their mouths and noses were closed. We suggest that the negative intrathoracic pressure due to the forced attempt to breathe in with voluntary diaphragmatic contractions contributes to alveolar hemorrhage, since it may damage the pulmonary capillaries.     

Large lungs in divers: natural selection or a training effect?

BACKGROUND: Normal spirometry is required for medical clearance of professional divers in many countries. Divers frequently have unusually large lung volumes associated with a low ratio of FEV(1) to FVC (FEV(1)%), suggestive of obstructive airways disease. We retrospectively analyzed the records of divers in the Israeli Navy with a low FEV(1)% who fulfilled the criteria for large lungs, to determine whether this might be the effect of training or natural selection. We also investigated changes in pulmonary function in relation to diving experience. METHODS: A total of 171 divers with FEV(1)% < 80% on simple spirometry were evaluated. We conducted a retrospective analysis of lung function data for those subjects who met the criteria for large lungs. RESULTS: One hundred nine of 171 divers with low FEV(1)% met the criteria for large lungs and were included in the study. Their average age was 25 years (range, 18 to 44 years), and their mean diving experience was 7 years (range, 0 to 26 years). No difference was found in FVC values between experienced and inexperienced divers. The mean forced expiratory flow at 50% of vital capacity was significantly reduced in the most experienced group compared with the novice or less experienced divers. No difference was found in the diffusing capacity of the lung for carbon monoxide between experienced and inexperienced divers. CONCLUSIONS: We suggest that large lungs may represent part of the natural selection for diving, rather than a training effect. Prolonged diving experience may result in the development of small airways disease.     

Glossopharyngeal insufflation causes lung injury in trained breath‐hold divers

Background and objective: Glossopharyngeal insufflation (GI) is a technique practised by competitive breath‐hold divers to enhance their performance. Using the oropharyngeal musculature, air is pumped into the lungs to increase the lung volume above physiological TLC. Experienced breath‐hold divers can increase their lung volumes by up to 3 L. Although the potential for lung injury is evident, there is limited information available. The aim of this study was to examine whether there is any evidence of lung injury following GI, independent of diving. Methods: Six male, competitive breath‐hold divers were studied. CT of the thorax was performed during breath‐holding at supramaximal lung volumes following GI (CT _GI ), and subsequently at baseline TLC (CT _TLC ). CT scans were performed a minimum of 3 days apart. Images were analysed for evidence of pneumomediastinum or pneumothorax by investigators who were blinded to the procedure. Results: None of the subjects showed symptoms or signs of pneumomediastinum. However, in five of six subjects a pneumomediastinum was detected during the CT _GI . In three subjects a pneumomediastinum was detected on the CT _GI , but had resolved by the time of the CT _TLC . In two subjects a pneumomediastinum was seen on both the CT _GI and the CT _TLC , and these were larger on the day that a maximal GI manoeuvre had been performed. The single subject, in whom a pneumomediastinum was not detected, was demonstrated separately to not be proficient at GI. Conclusions: Barotrauma was observed in breath‐hold divers who increased their lung volumes by GI. The long‐term effects of this barotrauma are uncertain and longitudinal studies are required to assess cumulative lung damage.     

Morphometrics of the avian lung. 4. The structural design of the charadriiform lung

The lungs of five charadriiform species of bird, two of which are good divers and three predominantly flyers (soarers and gliders) have been analysed by morphometric techniques. Largely the morphometric structural values in the divers significantly exceeded those of the flyers (gulls). The average weight specific surface area of the blood-gas (tissue) barrier in the divers (28.45 +/- 2.05 cm2 X g-1 SD) surpassed that of the flyers (23.5 +/- 3.61 cm2 X g-1 SD). The divers had a higher volume of the pulmonary capillary blood per unit body weight (4.42 +/- 0.11 cm3 X kg-1 SD) than the flyers (2.84 +/- 0.58 cm3 X kg-1 SD). The weight specific volume of the lung in the divers (34.90 +/- 3.11 cm3 X kg-1 SD) exceeded that of the flyers (26.94 +/- 3.15 cm3 X kg-1 SD). The total morphometric pulmonary diffusing capacity per unit body weight in the divers (4.73 +/- 0.05 ml O2 X (min X mm Hg X kg)-1 SD) was higher than that of the flyers (3.09 +/- 0.47 ml O2 X (min X mm Hg X kg)-1 SD). The divers, however, had a notably thicker blood-gas (tissue) barrier with a harmonic mean thickness of 0.212 +/- 0.03 micron SD compared to that of the flyers (0.138 +/- 0.02 micron SD). The data acquired here commensurate the modes of life exhibited by these two groups of bird. The divers, which are relatively energetic birds, expend a lot of energy to move and stay underwater, concomitantly undergoing prolonged asphyxia during submergence and may hence need to extract as much of the oxygen in the pulmonary air as possible to prolong a dive. These birds appear in general to have structurally better adapted lungs than those of the gulls, birds which to a large extent exhibit relatively less energetic soaring and gliding flights.     

Radiographic evidence of bronchopulmonary dysplasia in high-risk congenital diaphragmatic hernia survivors

Congenital diaphragmatic hernia is a congenital malformation associated with pulmonary hypoplasia. It often leads to respiratory failure, requiring artificial ventilation with high inflation pressures and high percentages of oxygen. We evaluated radiographic evidence of bronchopulmonary dysplasia (BPD) in survivors, who presented with respiratory distress within 6 hours after birth, by a radiographic scoring system measuring the severity of BPD by the Toce score and the degree of pulmonary hypoplasia by the Touloukian score. Fifteen of 45 survivors (33 percent) had clinical and radiological lung disease resembling BPD. As a group they had significantly higher Touloukian and Toce scores than survivors without BPD. Morbidity expressed as the duration of artificial ventilation, supplemental oxygen, and hospital stay was much higher in the BPD group. The hypoplastic lung in infants with congenital diaphragmatic hernia appears to be as susceptible to barotrauma and pulmonary oxygen toxicity as the lungs of prematurely born infants. To what extent BPD occurring in congenital diaphragmatic hernia survivors might influence the future development of lung function is not yet known. © 1993 Wiley-Liss, Inc.     

Differential effects of oxygen and barotrauma on lung injury in the neonatal piglet

In order to differentiate the effects of hyperoxia and barotrauma in the pathogenesis of acute neonatal lung injury, piglets were either hyperventilated (Paco2, 15-20 torr) for 48 hours with 100% oxygen (Group I), hyperventilated with 21% oxygen (Group II), normally ventilated (Paco2, 40-45 torr) with 100% oxygen (Group III), or normally ventilated with 21% O2 (Group IV) and compared to unventilated controls. Pulmonary function was tested, and biochemical indicators of lung injury were analyzed in tracheo-bronchial aspirates at 0, 24, and 48 hours. Bronchoalveolar lavage fluid was analyzed for surfactant composition and activity at the end of the study. At 48 hours, hyperoxic, hyperventilated piglets had significantly decreased dynamic lung compliance (30%) and increased pulmonary resistance (16%), aspirate cell count (190%), elastase activity (88%), albumin (214%), and total protein (150%) concentration. Qualitative light microscopy showed moderate to severe atelectasis, fibrinous exudate, edema, and inflammation. Normoxic, hyperventilated animals had comparable changes in pulmonary mechanics, but significantly milder cellular, biochemical, and morphologic changes. In hyperoxic, normocarbic animals pulmonary physiologic, cellular, and biochemical variables changed comparably to hyperoxic, hyperventilated animals; the pathologic changes were intermediate between hyperoxic, hyperventilated and normoxic, hyperventilated piglets. Normoxic, normocarbic animals had no significant changes in most variables over 48 hours; on morphologic examination their lungs were similar to unventilated controls and showed only mild edema. Surfactant had normal biophysical activity in all animals. Our results demonstrate that hyperoxia causes more significant physiologic, inflammatory, and histologic changes than barotrauma alone. Future attempts to prevent lung injury in neonates should be directed primarily at oxygen toxicity.     

Ten years of diving-related illness in the Royal Navy

The period from 1 January 1980 to 31 December 1989 produced a total of 244 training and operational diving accident reports involving Royal Navy and Royal Marines personnel. Because the incidence figures fluctuated widely year by year, a clear trend over the decade failed to emerge. However, the incidence of Type II decompression sickness, as a percentage of total decompression sickness, was greater in the second half of the decade than in the first, a trend similar to, although more moderate than, recent experience of dysbaric illness amongst sport divers. Student divers were disproportionately highly represented in the statistics, particularly with regard to pulmonary barotrauma and near-drowning.     

Connective tissue growth factor expression pattern in lung development

The aim of this study was to investigate the expression and distribution pattern of connective tissue growth factor (CTGF) in lung development during different stages, and to compare with a model of stimulated lung growth after tracheal ligation (TL) and with the teratogen model of induced congenital diaphragmatic hernia (CDH) and lung hypoplasia after nitrofen. Sprague-Dawley rat fetuses were obtained on gestational days 14, 17, and 21 (E14, E17, E21). For the experimental CDH group, pregnant rats were given 100 mg nitrofen on gestational day 9.5 (E9.5), and delivered E21. In another group, Sprague-Dawley rat fetuses were subjected to intrauterine tracheal ligation (TL) on gestational day 19 (E19), and delivered on day 21 (E21). All fetuses were delivered by cesarean section and lungs harvested. Lungs from 1-day-old newborn healthy, nonoperated rats were also obtained. Immunohistochemical (IHC) analysis for CTGF was performed on the different lung sections. CTGF mRNA expression levels in hyperplastic lungs after TL, hypoplastic lungs and CDH after nitrofen administration, and fetal controls at E21 were analyzed with real-time polymerase chain reaction (PCR). Immunohistochemical staining for CTGF at E14 showed that it was merely localized to the epithelium of terminal bronchiole, increasing during gestation, being more abundant at E17 and at E21. In the CDH group, lungs had an immature appearance and CTGF protein expression was decreased in the epithelium of the distal airways compared to the control group at E21, and was mainly observed in the lung mesenchyme. In the TL group, CTGF expression was more abundant compared to the control group at E21, especially in the epithelium of the terminal bronchioles, with a decreasing expression pattern distally. In the newborn lungs, CTGF had a pattern of expression in the epithelium of terminal bronchiole similar to TL lungs. At the mRNA level, CTGF expression was increased after TL, and decreased in the teratogen model of CDH and lung hypoplasia after nitrofen administration. This is, to the authors’ knowledge, the first report of CTGF expression pattern during lung development, and of an impaired expression in CDH lungs after nitrofen. CTGF is suggested to enhance alveologenesis and microvascular development at late stages of lung development, and a decreased expression could lead to the impaired alveologenesis and abnormal microvascular pulmonary bed observed in CDH lungs. Increased understanding of the molecular mechanisms that control lung growth could provide a key to develop novel therapeutic techniques to stimulate pre- and/or postnatal lung growth in infants with impaired lung growth and development, such in congenital diaphragmatic hernia.     

Effect of adenosine triphosphate-sensitive potassium channel openers on lung preservation

ATP-sensitive potassium channel (KATP) openers have been proven to be involved in ischemic preconditioning, which protects ischemic tissue. However, the effect of KATP openers on ischemia-reperfusion injury of the lungs remains unknown. We investigated whether a KATP opener, pinacidil, can attenuate ischemia-reperfusion injury using an ex vivo rat lung model. Heart-lung blocks were flushed and preserved with phosphate-buffered saline (control group) or with one of the solutions containing pinacidil (pinacidil group) or pinacidil + glibenclamide (a KATP blocker) (glibenclamide group). The control and glibenclamide groups showed significantly higher values with respect to shunt fraction, pulmonary arterial pressure, and peak inspiratory pressure than the pinacidil group. The concentrations of total adenine nucleotides and ATP in the lung after reperfusion became significantly lower in the control and glibenclamide groups than in the fresh group. Lipid peroxidation of the lungs increased significantly in the control and glibenclamide groups after reperfusion. State 3 mitochondrial respiration and State 3/4 ratios of mitochondrial respiration were significantly decreased in the lungs of the control and glibenclamide groups. These findings suggested that KATP openers would maintain the mitochondrial respiratory function during lung preservation, prevent lipid peroxidation after reperfusion, and attenuate ischemia-reperfusion injury.     

Lung injury following pulmonary resection in the isolated, blood-perfused rat lung.

Lung resection may be complicated by postpneumonectomy pulmonary oedema. Oxidant generation following surgery-induced ischaemia-reperfusion may be responsible. This hypothesis was tested utilizing isolated, in situ, blood perfused rodent lungs subjected to continuous perfusion (control subjects); one lung ventilation followed by pneumonectomy (group 1); or one lung ventilation followed by reinflation of the collapsed lung (group 2). In control subjects, no significant changes in markers of oxidant damage, oxygenation, pulmonary artery pressure or extravascular albumin extravasation were detected. In group 1 lungs, hydroxyl radical-like damage was detected in association with impaired oxygenation (p<0.05), and increased pulmonary artery pressure and extravascular albumin accumulation in both lungs. In group 2, there was evidence of hydroxyl radical-like damage, and a fall in oxygenation (p<0.05) occurred during one lung ventilation. There was a transient rise in pulmonary artery pressure following lung reinflation and extra vascular albumin accumulation was significantly increased in both lungs (right>left, p<0.05). Both changes were attenuated (p<0.05) following treatment with the reactive oxygen species (ROS) scavenger superoxide dismutase (group 2a) and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (group 2b). Hydroxyl radical-like damage was undetectable following nitric oxide synthase inhibition. Oxidant stress may contribute to the pathologies seen in this model of lung injury.     

Glutathione decreases the pulmonary reimplantation response in canine lung autotransplants

The pulmonary reimplantation response (PRR) is a form of membrane permeability pulmonary edema occurring in lung transplants. The severity of the PRR reflects the quality and duration of lung graft preservation. Free radicals formed during ischemia with reperfusion in the autotransplanted dog lung may play a role in producing PRR. We hypothesized that the addition of reduced glutathione (GSH) to the preservative solution could decrease PRR if hydroperoxides are being formed. Six dogs underwent left lung autotransplantation after the lung was flushed with Euro-Collins solution (EC). These dogs demonstrated radiographic and histopathologic evidence of bilateral pulmonary edema, greatest in the transplanted left lung. They also had increases in lung wet to dry weight (W/D) ratios in both lungs (left, 12.0 +/- 0.9; right, 10.1 +/- 0.8) as compared with a group of five unmanipulated control animals (left, 6.0 +/- 0.5; right, 7.0 +/- 0.4). Malondialdehyde (MDA) concentrations were significantly increased in the transplanted left lungs (14 +/- 4) from this group as compared with the controls (5 +/- 7). Five additional dogs underwent left lung autotransplantation with GSH added to the EC cryopreservation fluid. These animals did not develop histologic or radiographic evidence of pulmonary edema, and W/D ratios as well as MDA concentrations were not different from those in controls. To evaluate the effect of ischemia alone on changes in lung GSH concentrations, ten additional dogs underwent left pneumonectomy. Left lungs were cryopreserved in EC + GSH. In five of the animals, the right lung was removed and preserved in EC alone. In the other five animals, the right lung remained in vivo for 3 h and was then removed. Lung GSH concentrations were doubled after 3 h of ischemia when incubated in EC + GSH compared to in vivo controls and to EC-treated lungs. These data suggest that GSH added to the preservation fluid prevents PRR following transplantation and that lung GSH concentrations actually increase during preservation prior to reimplantation and reperfusion if the lung graft is exposed to GSH in the preservation fluid.     

Recreational scuba diving, patent foramen ovale and their associated risks

Scuba diving has become a popular leisure time activity with distinct risks to health owing to its physical characteristics. Knowledge of the behaviour of any mixture of breathable gases under increased ambient pressure is crucial for safe diving and gives clues as to the pathophysiology of compression or decompression related disorders. Immersion in cold water augments cardiac pre- and afterload due to an increase of intrathoracic blood volume and peripheral vasoconstriction. In very rare cases, the vasoconstrictor response can lead to pulmonary oedema. Immersion of the face in cold water is associated with bradycardia mediated by increased vagal tone. In icy water, the bradycardia can be so pronounced, that syncope results. For recreational dives, compressed air (i.e., 4 parts nitrogen and 1 part oxygen) is the preferred breathing gas. Its use is limited for diving to 40 to 50 m, otherwise nitrogen narcosis ("rapture of the deep") reduces a diver's cognitive function and increases the risk of inadequate reactions. At depths of 60 to 70 m oxygen toxicity impairs respiration and at higher partial pressures also functioning of the central nervous system. The use of special nitrogen-oxygen mixtures ("nitrox", 60% nitrogen and 40% oxygen as the typical example) decreases the probability of nitrogen narcosis and probably bubble formation, at the cost of increased risk of oxygen toxicity. Most of the health hazards during dives are consequences of changes in gas volume and formation of gas bubbles due to reduction of ambient pressure during a diver's ascent. The term barotrauma encompasses disorders related to over expansion of gas filled body cavities (mainly the lung and the inner ear). Decompression sickness results from the growth of gas nuclei in predominantly fatty tissue. Arterial gas embolism describes the penetration of such gas bubbles into the systemic circulation, either due to pulmonary barotrauma, transpulmonary passage after massive bubble formation ("chokes") or cardiac shunting. In recreational divers, neurological decompression events comprise 80% of reported cases of major decompression problems, most of the time due to pathological effects of intravascular bubbles. In divers with a history of major neurological decompression symptoms without evident cause, transoesophageal echocardiography must be performed to exclude a patent foramen ovale. If a cardiac right-to-left shunt is present, we advise divers with a history of severe decompression illness to stop diving. If they refuse to do so, it is crucial that they change their diving habits, minimising the amount of nitrogen load on the tissue. There is ongoing debate about the long term risk of scuba diving. Neuro-imaging studies revealed an increased frequency of ischaemic brain lesions in divers, which do not correlate well with subtle functional neurological deficits in experienced divers. In the light of the high prevalence of venous gas bubbles even after dives in shallow water and the presence of a cardiac right-to-left shunt in a quarter of the population (i.e., patent foramen ovale), arterialisation of gas bubbles might be more frequent than usually presumed.     

通气状态下离体肺保存的实验研究

目的应用兔离体肺再灌注模型研究通气在离体肺保护中的作用。方法10只实验用兔20个单肺,分成A、B两组。A组为通气状态下低温再灌注组;B组为单纯低温再灌注组。分别在保存0、3、6．9、12、15、18h时取保存组织送组织学检查及引流灌注液测血气分析。结果在保存9h时A、B两组组织学结构发现差别,A组优于B组。血气分析示：A、B两组二氧化碳分压及PH无明显差别,氧分压有显著差别。结论在通气状态下低温灌注保存离体肺的效果明显优于单纯低温灌注保存方法。在通气状态下低温灌注保存离体肺的有效时限可达18h。     

Pulmonary edema after pulmonary artery occlusion and reperfusion

We examined the basis of reperfusion-induced pulmonary edema produced by pulmonary artery occlusion and subsequent reperfusion. After a 24-h period of occlusion of a rabbit pulmonary artery followed by a 2-h period of reperfusion, the lungs were removed from the animal and perfused with a 0.5 g% Ringer's-albumin solution. An increase in lung weight was observed within 60 min compared with control lungs (i.e., lungs subjected to pulmonary arterial occlusion but not reperfusion) (p less than 0.05). Shorter periods of occlusion (6 or 12 h) did not result in edema, which suggests that a period of ischemia was required for the reperfusion-induced pulmonary edema. The extravascular lung water content also increased in the contralateral lung (i.e., the lung not subjected to pulmonary arterial occlusion and reperfusion). The capillary filtration coefficient increased in reperfused lungs compared with controls (p less than 0.05), indicating an increase in lung vascular permeability following reperfusion. Infusion of allopurinol (a xanthine oxidase inhibitor) and superoxide dismutase during the reperfusion period prevented the increases in lung weight and vascular permeability; infusion of catalase was ineffective. We conclude that pulmonary reperfusion following pulmonary artery occlusion increases pulmonary vascular permeability, which is mediated by the generation of oxidants.     

Patent foramen ovale in scuba divers. A report of two cases and a brief review of the literature.

Scuba diving (diving with a self-contained underwater breathing apparatus) has become a popular sport. Decompression illness may be due to the formation of gas bubbles in various body tissues at an increased ambient pressure. The gas can pass from the systemic venous circulation into the arterial circulation as a result of either pulmonary barotrauma or intravascular shunting. Gas emboli may be the cause of an increased prevalence of brain lesions in sport divers. The management of scuba divers (professionals and amateurs) with a patent foramen ovale is not clear. We present the cases of 2 subjects with decompression illness and a patent foramen ovale and briefly review the literature on this combination.     

Biodistribution in mice and severity of damage in rat lungs following pulmonary delivery of 9-nitrocamptothecin liposomes

This study was designed to investigate in vitro release, in vivo tissue distribution and the damage to the lungs of 9-nitrocamptothecin (9-NC) liposomes. In vitro release of 9-NC from liposomes was carried out in phosphate buffer saline solution (PBS) pH 7.4. The tissue distribution of 9-NC liposomes and 9-NC solution was determined after pulmonary delivery to mice. The tissue distribution of 9-NC liposomes after intravenous administration was also studied. The changes of pulmonary edema index and histology of lungs in rats were investigated to evaluate the severity of the damage after pulmonary delivery. The results showed that 9-NC was continuously released from liposomes in PBS pH 7.4 for 24h at 37 degrees C. After pulmonary delivery, the mean residence time (MRT) of 9-NC liposomes in the lungs was 3.4 times as long as that of 9-NC solution and the total AUC0-t of all tissues in mice of the liposomes was 2.2-fold higher than that of the solution, indicating that the liposomes had sustained-release characteristics. Following intravenous administration and pulmonary delivery, the targeting efficiency (Te) to the lung of 9-NC liposomes was 0.14 and 2.02, respectively, which showed that intratracheal instillation can deliver the drug mainly to the lung and decrease the accumulation of the drug in other tissues at different concentrations. The pulmonary edema index and the histological changes of the lungs in 9-NC liposome group were significantly different from those in 9-NC solution group. The lung damage by liposomes was less severe than that by solution. Pulmonary delivery of 9-NC liposomes could directly deliver the drug to the lung and make the drug accumulate in the lung with sustained-release characteristics, changing the disposition behavior in vivo, decreasing the toxic and side effects on other tissues and reduce the severity of damage to lungs following intratracheal instillation.     

Effect of edema on segmental vascular resistance in isolated perfused rat lungs

We have determined the effect of hydrostatic edema on total and segmental vascular resistances in the rat lung. Lungs of 12 adult rats, body weight 515 +/- 42 g, were isolated and perfused with blood. To investigate the role of vasoactivity on edema effects, we studied two groups of lungs; group I (n = 6) were untreated and group II (n = 6) were treated with papaverine hydrochloride to paralyze the vasculature. Initially blood flow was adjusted to keep pulmonary artery pressure approximately 15 cmH2O, left atrial and airway pressures being 8 and 7 cmH2O, respectively, and then kept unchanged thereafter (18 +/- 3 ml/kg/min). Hydrostatic edema was induced by raising venous pressure and pulmonary artery pressure measured continuously. In 4 lungs from each group, during baseline and after the development of severe edema, we partitioned the pulmonary circulation into arteries, microvessels, and veins by measuring pressures in 20-50 microns diameter subpleural arterioles and venules with the micropipette-Servonull method. Baseline total vascular resistance was similar in the two groups. Interstitial and early alveolar edema did not affect pulmonary vascular pressures. With severe edema (W/D ratio: 17 +/- 2), pressures in pulmonary artery and arterioles increased significantly in both groups; venular pressures did not change. Total resistance increased by 250% in group I and by 224% in group II lungs. Arterial resistance increased 3-5-fold in both groups, as did microvascular resistance. Venous resistances also increased in both groups, although to a lesser extent. The increase in total and segmental vascular resistances was not significantly different in the two groups of lungs. We conclude that in isolated rat lungs only severe edema results in an increase in total vascular resistance, mainly due to an increase in arterial and microvascular resistances, with a smaller increase in venous resistance. This appears to be a mechanical effect of edema on the vasculature and not a result of active vasomotion.     

Mechanical ventilation-induced air-space enlargement during experimental pneumonia in piglets

Mechanical ventilation-induced air-space enlargement was investigated in a porcine model of multifocal pneumonia. Following the intrabronchial inoculation of Escherichia coli, 9 piglets (22 +/- 2 kg) were ventilated with a tidal volume (VT) of 15 ml/kg for 43 +/- 15 h. Five noninoculated piglets ventilated for 60 h with the same VT served as control animals. Following death, the lungs were fixed and lung morphometry was assessed. In inoculated animals, unventilated infected and normally ventilated noninfected pulmonary lobules coexisted. In normally ventilated lung regions (1) emphysema-like lesions were present, (2) mean alveolar area and mean linear intercept were significantly greater in inoculated than in control animals, and (3) the degree of alveolar distension correlated with the decrease in respiratory compliance. In unventilated lung areas (1) pseudocysts were frequent, (2) alveolar edema was rare, (3) bronchiolectasis was frequent, (4) mean bronchiolar area was greater in inoculated than in control animals, and (5) the degree of bronchiolar distension correlated with the increase in inspiratory plateau pressure. In conclusion, in piglets with severe bronchopneumonia, air-space enlargement rather than pulmonary edema was the major feature of mechanical ventilation-induced lung barotrauma and resembled lesions previously reported in critically ill patients ventilated using high inspiratory pressures.