Acute pneumonia reversibly inhibits hypoxic vasoconstriction in isolated rat lungs.

Pneumonia was induced in rats by instillation of carrageenin (0.5 ml of 0.7% solution) into the trachea. Three or four days after instillation, the lungs were isolated, perfused with blood of healthy rat blood donors, and ventilated with air + 5% CO2 or with various hypoxic gas mixtures. Pulmonary vascular reactivity to acute hypoxic challenges was significantly lower in lungs of rats with pneumonia than in lungs of controls. The relationship between O2 concentration in the inspired gas and Po2 in the blood effluent from the preparation was shifted significantly to lower Po2 in lungs with pneumonia compared to control ones. These changes were not present in rats allowed to recover for 2-3 weeks after carrageenin instillation. We suppose that blunted hypoxic pulmonary vasoconstriction may contribute to hypoxaemia during acute pulmonary inflammation. Decreased Po2 in the blood effluent from the isolated lungs with pneumonia implies significant increase of oxygen consumption by the cells involved in the inflammatory process.     

The content of prostaglandin E and prostaglandin F2alpha in the exudate of carrageenin granuloma of rats.

1.Granuloma was made by the subcutaneous injection of 2% carrageenin solution on the dorsum of male rats. Eight, 16, 24 and 72 h after the injection. the exudate from each rat granuloma was withdrawn and extracted for rpstaglandins. 2.Extracted prostaglandins were separated prostaglandin E and prostaglandin F group by silicic acid mini-column chromatography. Then the amount of prostaglandin E and prostaglandin F2alpha were determined by the radioimmunoassay method. 3.The levels of prostaglandin E in the granuloma exudates were 4.6 ng/ml at 8 h after the carrageenin injection, then decreased 3.6 ng/ml and to 1.1 ng/ml at 16 h and 24 h, respectively. Seventy-two h after the injection, prostaglandin E level was increased to 8.1 ng/ml. 4.The levels of prostaglandin F2alpha in the exudate were as follows: At 8 h after the carrageenin injection, the level was 9.4 ng/ml, then decreased to 1.3 ng/ml and to 0.8 ng/ml at 16 h and 24 h, respectively. Seventy-two h after the carrageenin injection, it was again elevated to 4.7 ng/ml. 5.The exudate of granuloma, 24 and 72 h after the carrageenin injection, was incubated with [3H]prostaglandin E1 at 37 degrees C for 30 min. Then the acidic ether extract was subjected to reversed phase partition chromatography. It was found that the exudate of 24 h and 72 h granuloma had little activity of prostaglandin 15alpha-hydroxy dehydrogenase.     

Lung function in acute paraquat intoxication.

Functional and morphological examination of the lungs was performed in rats 48 hours after intratracheal injection of 0.5 mg/kg of the herbicide paraquat. Pronounced tachypnoea was observed (235+/-20 c/min), which also persisted under urethane anaesthesia (210+/-18 c/min). In control rats the mean breathing rate was 115+/-11 and 90+/-9 c/min in wake and anaesthetized rats respectively. The rate of breathing decreased to comparable values in experimental and control rats after bilateral cervical vagotomy. The functional residual lung capacity was significantly increased in experimental rats. After vagotomy also this increase of functional residual capacity became normalized. Histologically the disease was characterized by focal formation of hyaline membranes and oedema with occasional haemorrhages and signs of inflammation. The significant role fo vagal function in lung pathology is demonstrated.     

Effect of Bordetella heat-labile toxin on perfused lung preparations of guinea pigs

In vitro effects of the Bordetella HLT on the isolated perfused lung and some other tissue preparations from guinea pigs were examined. When HLT (30 to 300 MNDs/ml) was administered, an increase of the perfusion pressure was induced in the perfused lungs, indicating vasoconstriction. When 100 or 300 MNDs/ml of HLT was given, the pressure increase appeared after a lag period of 3.5 to 4 min, reached a maximum within 8 to 13 min, and then slowly decreased by 60 to 80% 25 min after exposure. In calcium-free medium, the pressure increase due to HLT did not occur, but these HLT-treated lungs manifested an increase without any lag period immediately after the calcium-free medium was replaced by normal medium containing calcium. No difference in the response of the perfused lungs to histamine was observed before and after exposure to HLT. The arterial strip did not respond to HLT, but after predigestion with a collagenase and elastase solution the contractive response to 100 MNDs/ml of HLT appeared with a lag period of 1 min. HLT had no effect on the pharmacological responses of the isolated atria, deferent canal or intestinal preparations, or on the ciliary movement of cultured tracheal rings.     

Pulmonary mechanics during rapid mechanical ventilation in rabbits with saline-lavaged lungs

Infants with respiratory failure are frequently mechanically ventilated at rates exceeding 60 breaths/min. We analyzed the effect of ventilatory rates of 30, 60, and 90 breaths/min (inspiratory times of 0.6, 0.3, and 0.2 s, respectively) on the pressure-flow relationships of the lungs of anesthetized paralyzed rabbits after saline lavage. Tidal volume and functional residual capacity were maintained constant. We computed effective inspiratory and expiratory resistance and compliance of the lungs by dividing changes in transpulmonary pressure into resistive and elastic components with a multiple linear regression. We found that mean pulmonary resistance was lower at higher ventilatory rates, while pulmonary compliance was independent of ventilatory rate. The transpulmonary pressure developed by the ventilator during inspiration approximated a linear ramp. Gas flow became constant and the pressure-volume relationship linear during the last portion of inspiration. Even at a ventilatory rate of 90 breaths/min, 28-56% of the tidal volume was delivered with a constant inspiratory flow. Our findings are consistent with the model of Bates et al. (J. Appl. Physiol. 58: 1840-1848, 1985), wherein the distribution of gas flow within the lungs depends predominantly on resistive factors while inspiratory flow is increasing, and on elastic factors while inspiratory flow is constant. This dynamic behavior of the surfactant-depleted lungs suggests that, even with very short inspiratory times, distribution of gas flow within the lungs is in large part determined by elastic factors. Unless the inspiratory time is further shortened, gas flow may be directed to areas of increased resistance, resulting in hyperinflation and barotrauma.     

Resistance of isolated pulmonary mitochondria during in vitro anoxia/reoxygenation

The aim of the study was to investigate the effect of in vitro anoxia/reoxygenation on the oxidative phosphorylation of isolated lung mitochondria. Mitochondria were isolated after harvesting from fresh pig lungs flushed with Euro-Collins solution. Mitochondrial respiratory parameters were determined in isolated mitochondria before anoxia (control), after 5-45 min anoxia followed by 5 min reoxygenation, and after 25 or 40 min of in vitro incubation in order to follow the in vitro aging of mitochondria during respiratory assays. Respiratory parameters measured after anoxia/reoxygenation did not show any oxidative phosphorylation dysfunction, indicating a high resistance of pulmonary mitochondria to in vitro anoxia/reoxygenation (up to 45 min anoxia). These results indicate that mitochondria are not directly responsible of their oxidative phosphorylation damage observed after in vivo ischemia (K. Willet et al., Transplantation 69 (2000) 582) but are a target of others cellular injuries leading to mitochondrial dysfunction in vivo.     

Pleural surface fluorescence measurement of Na+ and Cl- transport across the air space-capillary barrier.

We developed a pleural surface fluorescence method to measure Na(+) and Cl(-) transport in perfused mouse lungs. The air space was filled with aqueous fluid containing membrane-impermeant fluorescent indicators of Cl(-) (lucigenin) or Na(+) (Sodium Green). After instillation of a Cl(-)-free solution into the air space, an increase in perfusate Cl(-) concentration from 0 to 30 mM produced a decrease in surface lucigenin fluorescence (6.5%/min) corresponding to Cl(-) influx of 1.0 mM/min. Cl(-) influx was increased to 2.1 +/- 0.3 mM/min by forskolin, and the increase was inhibited by glibenclamide. cAMP-stimulated Cl(-) influx was decreased by 57% in CFTR null mice. After instillation of a Na(+)-free solution into the air space, an increase in perfusate Na(+) concentration from 0 to 30 mM gave increased Sodium Green fluorescence (Na(+) influx of 1.2 mM/min), which increased approximately fivefold after cAMP agonists. Cl(-) and Na(+) transport were not affected in lungs from mice lacking aquaporins AQP1 or AQP5. Our results establish a pleural surface fluorescence method to measure unidirectional Cl(-) and Na(+) flux in intact lung and provide evidence for cAMP-stimulated transcellular Cl(-) and Na(+) transport.     

急性减压病大鼠肺组织粘附分子的变化

目的:探讨急性减压病大鼠肺组织中内粘附分子的改变。方法:雄性SD大鼠置于加压舱内,压缩空气在3 min内匀速加压至0.7 MPa,停留60 min后,3 min内快速减压出舱。观察减压后生存率、减压病症状。在减压后30 min、6 h、24 h取大鼠脑、肺及肝脏组织,甲醛溶液固定、切片、HE染色观测病理改变。免疫组化测定肺组织中细胞间粘附分子-1(ICAM-1)、E-选择素(E-selectin)、主要组织相容性复合体-Ⅱ(MHC-Ⅱ)的表达变化。在减压后6h、24 h前30 min,大鼠尾静脉注射2%evans blue溶液。30 min后行生理盐水灌注,收集肺组织,观测肺组织蓝染程度,酶标仪测定血浆中evans blue含量。结果:肺、肝及脑组织在减压后30 min出现水肿、淤血等病理表现。和正常组比较,肺组织中ICAM-1、E-selectin、MHC-Ⅱ在减压后明显上升,并呈现动态变化。相对于正常组,减压后6 h、24h肺组织血浆中evans blue含量明显增加。结论:气泡导致的,粘附分子介导的血管内皮受损是减压病的发病机制之一。     

Rapid increases in respiratory epithelial permeability occur after intratracheal instillation of PMA

We measured pulmonary epithelial permeability by quantifying the disappearance of two water-soluble compounds, [14C]mannitol and [3H]inulin, after their instillation, with and without phorbol myristate acetate (PMA), into gas-filled perfused (50 ml/min) rabbit lungs in situ. Both tracers disappeared in a monoexponential fashion over 30 min with calculated first-order rate constants (control; n = 11) of 0.0008 +/- 0.0002 and 0.0027 +/- 0.0008 min-1 for inulin and mannitol, respectively. The ratio of the rate constants (3.1 +/- 0.5) was not significantly different from the ratio of diffusivities of mannitol:inulin (3.7). Addition of PMA (250 micrograms) significantly (n = 9, P less than 0.05) increased the rate constants for both inulin and mannitol to 0.0024 +/- 0.0007 and 0.0087 +/- 0.0025 min-1, respectively, while not affecting their ratio (4.3 +/- 0.5). Addition of human leukocytes (4-8 X 10(8)/l) to the perfusate did not exacerbate the effect of 250 micrograms PMA (n = 3). The addition of catalase (n = 7) completely inhibited the effect of 250 micrograms PMA. PMA (250 micrograms) did not significantly affect perfusion pressure but increased wet-to-dry weight ratios. Light microscopic histology showed damage to epithelial and endothelial cells after 250 micrograms PMA which was not seen after coinstillation of catalase. Catalase sensitivity of functional and structural effects of PMA suggests that the effect was secondary to production of hydrogen peroxide. Since this effect was noted in lungs not perfused with neutrophils and addition of leukocytes did not exacerbate the increase in permeability, we hypothesize that an undetermined pulmonary cell type was the source of hydrogen peroxide. Finally, we found no evidence for restrictive pores with radii of 0.4-1.4 nm.     

Direct demonstration of 25- and 50-microm arteriovenous pathways in healthy human and baboon lungs

Postmortem microsphere studies in adult human lungs have demonstrated the existence of intrapulmonary arteriovenous pathways using nonphysiological conditions. The aim of the current study was to determine whether large diameter (>25 and 50 microm) intrapulmonary arteriovenous pathways are functional in human and baboon lungs under physiological perfusion and ventilation pressures. We used fresh healthy human donor lungs obtained for transplantation and fresh lungs from baboons (Papio c. anubis). Lungs were ventilated with room air by using a peak inflation pressure of 15 cm H(2)O and a positive end-expiratory pressure of 5 cm H(2)O. Lungs were perfused between 10 and 20 cm H(2)O by using a phosphate-buffered saline solution with 5% albumin. We infused a mixture of 25- and 50-microm microspheres (0.5 and 1 million total for baboons and human studies, respectively) into the pulmonary artery and collected the entire pulmonary venous outflow. Under these conditions, evidence of intrapulmonary arteriovenous anastomoses was found in baboon (n = 3/4) and human (n = 4/6) lungs. In those lungs showing evidence of arteriovenous pathways, 50-microm microspheres were always able to traverse the pulmonary circulation, and the fraction of transpulmonary passage ranged from 0.0003 to 0.42%. These data show that intrapulmonary arteriovenous pathways >50 microm in diameter are functional under physiological ventilation and perfusion pressures in the isolated lung. These pathways provide an alternative conduit for pulmonary blood flow that likely bypasses the areas of gas exchange at the capillary-alveolar interface that could compromise both gas exchange and the ability of the lung to filter out microemboli.     

Cardiopulmonary function of dogs with plutonium-induced chronic lung injury

Beagle dogs had signs of restrictive lung disease 1 to 5 years after exposure by inhalation to 239PuO2 aerosols. The 239PuO2 aerosols were monodisperse with activity median aerodynamic diameters of 0.75, 1.5, or 3.0 microns. The plutonium particles produced protracted alpha irradiation of the lungs. Ten dogs had specific initial pulmonary burdens (IPB) of 330 to 4,100 kBq of 239PuO2/kg of body mass. The average onset time of clinical signs of lung injury was 3 years after exposure; the average time from the onset of signs until cardiorespiratory function evaluation was 5.5 years. A second group of 10 dogs had IPB of 110 to 2000 kBq of 239Pu/kg of body mass but no signs of lung injury. A third group of 10 dogs, not exposed to 239Pu, were matched for age and sex. Cardiopulmonary function tests were performed. Only the dogs in group I with signs of lung injury had a mild respiratory function disorder consisting of smaller lung volumes, reduced compliance, increased respiratory frequency and minute volume, and reduced carbon monoxide diffusing capacity. Cardiac function of all three groups was similar. These findings indicate that alpha irradiation of the lungs of man could produce restrictive lung disease at long times after initial exposure.     

Tuberous sclerosis with pulmonary involvement.

Pulmonary tuberous sclerosis produced interstitial disease in a woman with normal-sized lungs; numerous hemosiderin-laden macrophages were found in the fluid obtained through bronchoalveolar lavage. The pathological changes seen in the lungs were identical to those of pulmonary lymphangiomyomatosis, in which the constellation of clinical signs usually found in tuberous sclerosis is absent. The two conditions are sufficiently similar in clinical presentation, pathological changes and prognosis to be considered variants of the same disease. The recent findings of progestin receptors in lung tissue from patients with pulmonary lymphangiomyomatosis will likely direct future management towards hormonal manipulation.     

Acute and long-term TNF-alpha administration increases pulmonary vascular reactivity in isolated rat lungs.

Tumor necrosis factor-alpha (TNF-alpha) causes pulmonary hypertension and arterial hypoxemia, but the mechanisms are unknown. We conducted two experiments to test the hypothesis that TNF-alpha alters pulmonary vascular reactivity, which in turn could cause either pulmonary hypertension or arterial hypoxemia. In experiment 1, rats were given acute or long-term injections of TNF-alpha (recombinant human) in vivo. Rats treated acutely received either saline or TNF-alpha (40 micrograms/kg iv in saline) 3 min (TNF-3 min; n = 8), 20 min (TNF-20 min; n = 8), or 24 h (TNF-24 h; n = 5) before the lungs were isolated. Rats treated chronically received injections of either saline or TNF-alpha (250 micrograms/kg ip in saline) two times per day for 7 days (TNF-7 days; n = 9). Lungs were isolated and perfused with Earle's salt solution (+2 g/l NaHCO3 + 4 g/100 ml Ficoll), and vascular reactivity was tested with acute hypoxia (3 min; 3% O2) and angiotensin II (ANG II; 0.025-0.40 micrograms). Pulmonary pressor responses to hypoxia were greater (P less than 0.05) in TNF-20 min and TNF-7 day groups. ANG II responses were increased (P less than 0.05) in TNF-7 day rats. In experiment 2, lungs were isolated and perfused and received direct pulmonary arterial injections of TNF-alpha (0.2, 2.0, and 20 micrograms) or saline, after stable responses to hypoxia and ANG II (0.10 microgram) were attained. Reactivity was not different between control and TNF-alpha rats before the injections, but TNF-alpha increased (P less than 0.05) responses to hypoxia and ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)     

Massive postmortem bronchoconstriction in guinea pig lungs

A special phenomenon (difficult to inflate and deflate) occurring in the postmortem guinea pig lungs was studied in 40 animals. Thirty minutes after excision of the lungs or exsanguination, less than 50% of the lungs could be inflated even at high inflation pressure (34 cmH2O), and most gas was trapped during deflation. The amount of trapped gas volume at 30 min was related to the degree of lung inflation maintained during the 5- to 30-min period after exsanguination. Since stiffness of the lung tissue was unlikely to explain the phenomenon, we speculated airway obstruction as the major factor. No foam or bubbles were found in larger airways and we thus hypothesized that the obstruction was due to bronchoconstriction. This was confirmed histologically in that the lumina of both bronchi and bronchioles were constricted. The latent period to the onset of this constriction was short (approximately 5 min). It was not associated with O2 availability but was delayed an additional 15 min by a thromboxane inhibitor (dazoxiben). Neither maintaining lung temperature at 37 degrees C nor vagotomy and/or cervical transection prevented the constriction. Without exsanguination, onset of bronchoconstriction was delayed by about 1 h. We conclude that postmortem bronchoconstriction may be caused by release of an endogenous constrictor agent.     

Changes in airway resistance by simultaneous exposure to TNF-alpha and IL-1beta in perfused rat lungs

Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta are formed simultaneously under inflammatory conditions such as asthma and acute respiratory distress syndrome. Here we investigated the effects of TNF-alpha (10 ng/ml) and/or IL-1beta (10 ng/ml) in isolated blood-free perfused rat lungs. In lungs precontracted with methacholine, IL-1beta alone and IL-1beta/TNF-alpha decreased airway resistance 10 min after administration, whereas TNF-alpha alone had no effect. In untreated lungs, airway resistance was unaltered by either cytokine alone but started to increase 40 min after treatment with both cytokines together, indicating bronchoconstriction. The bronchoconstriction was accompanied by a steroid-sensitive increase in cyclooxygenase (COX)-2 mRNA expression and thromboxane formation. The cytokine-induced bronchoconstriction was blocked by the thromboxane receptor antagonist SQ-29548, indomethacin, the selective COX-2 inhibitor NS-398, and the steroid dexamethasone. We conclude that IL-1beta has an early bronchodilatory effect (after 10 min) that is unchanged by TNF-alpha. However, at later time points (after 40 min), IL-1beta and TNF-alpha in concert cause a COX-2- and thromboxane-dependent bronchoconstriction. Our findings show that TNF-alpha and IL-1beta exert complex and time-dependent effects on lung functions that cannot be predicted by studying each cytokine alone.     

Collagenolytic activity of carrageenin granuloma in rats.

Collagenolytic activity at various phases of the development of carrageenin granuloma was investigated by measuring the amount of dialysable hydroxyproline formed during incubation in vitro of minced granulation tissue. Collagenolytic activity reached a maximum at day 8 after carrageenin injection and then decreased gradually, while collagen synthetic activity was rapidly decreased from day 4 to day 11. The significance of dialysable hydroxyproline in native collagen breakdown of carrageenin granuloma is discussed.     

Collagenolytic activity of carrageenin granuloma in rats

Collagenolytic activity at various phases of the development of carrageenin granuloma was investigated by measuring the amount of dialysable hydroxyproline formed during incubation in vitro of minced granulation tissue. Collagenolytic activity reached a maximum at day 8 after carrageenin injection and then decreased gradually, while collagen synthetic activity was rapidly decreased from day 4 to day 11. The significance of dialysable hydroxyproline in native collagen breakdown of carrageenin granuloma is discussed.     

Effect of dexamethasone on carrageenin-induced inflammation in the lung

To study the anti-inflammatory mechanisms of glucocorticoids, we have compared the effects of intratracheal carrageenin (2.5 mg) on control rats and those in which inflammation was subdued by prior dexamethasone treatment (10 mg/l in drinking water). Inflammation was maximal 48 h post-carrageenin. After dexamethasone, carrageenin caused tittle inflammation or oedema (wet lung (mg), n = 6, mean +/- S.E.M.; control, 995 +/- 51; carrageenin + dexamethasone, 1144 +/- 83; compared with carrageenin alone, 1881 +/- 198), but rats had more lung lavage neutrophils than those given carrageenin alone (PMN x 10(6) /lung, mean +/- S.E.M.; control, 0.055 +/- 0.003; carrageenin + dexamethasone, 8.54 +/- 1.52; compared with carrageenin alone, 6.30 +/- 1.71). Proteolysis and partial inactivation of the anti-inflammatory mediator, lipocortin 1 (Lcl), in carrageenin-instilled rats was offset in those also given dexamethasone, by increased Lc1 levels (intact Lc1 ng/ml lavage fluid, n = 4, mean +/- S.E.M.; control 24 +/- 6; carrageenin 15 +/- 4; carrageenin + dexamethasone, 40 +/- 15). Maintenance of sufficient intact (fully active) extracellular Lc1 may contribute to the actions of glucocorticoids.     

圆斑蝰蛇(Vipera russelli siamensis)咬伤引起严重肺出血的报告

患者 :男 ,4 2岁 ,广西农民 ;2 0 0 3年 5月 2 5日下午 5时在工地捕捉 1条约 4 0 cm长蝰蛇时不慎被其咬伤 ,局部肿胀疼痛 ,下午 7时即转送来我院急诊。检查右手大鱼际可见牙痕 1个 ,渗血及皮下瘀血少许 ,肿至腕关节。牙龈出血 ,PT:>2 min (对照 11.9s) ;Fg:0 .0 g/L;尿隐血 ( )。第 2天 (伤后13h)觉胸闷、气紧、咳嗽、咯血 ,即给予查胸片 ,示右上、中肺可见模糊片状影。第 3天胸闷、气紧加重 ,出现两肺出血所致呼吸功能不全 ,复查胸片示病灶比前增多 ,右肺及左下肺可见斑片状边缘模糊阴影。咳嗽、气紧、咯血为鲜红色伴有少许血块 ,两肺可闻湿性罗音 ,心率 110次 /分 ,律整 ,血氧饱和度为 85%～ 90 %。经地塞米松、山茛菪碱、止血、抗感染等治疗 10天 ,症状体征消失 ,治愈出院     

Changes in integrated vagal afferent activity induced by model lung diseases in rats.

An attempt has been made in the present report to evaluate quantitatively the sensory activity in both vagal nerves of control rats and rats with experimental lung inflammation, by employing the integration technique. We evaluated background vagal nerve activity, resting respiration and activity during inflation at constant pressures of 5 to 20 cm of water. It was found that integrated vagal respiratory activity cannot be assessed in absolute units under our experimental conditions, because of the large scatter of data. However, when the integrated values were related, for example, to resting respiration (in percentage), it was possible to compare some respiratory parameters in control, healthy rats of the Wistar strain and rats with lung inflammation. While background activity in control rats represents 75.9% of resting respiration, this parameter is significantly higher both in rats with 2-day carrageenin lung inflammation and those intoxicated with paraquat. Lung inflation at pressures 5, 10, 15, 20 cm H2O increased vagal activity linearly both in control and the two experimental groups with the degree of lung inflation. However, values in experimental animals corresponding to those of the control group were not reached until higher inflation pressures. From the functional aspect, experimental rats had characteristic tachypnoea which returns to control values after bilateral vagotomy. Since it was found that lung compliance was significantly decreased in both carrageenin and paraquat lung processes, it is being suggested that the diminished activity from lung receptors during inflation is due to mechanical properties of the lung tissue, namely lowered lung compliance.