Increases in lung and brain water following experimental stroke: effect of mannitol and hypertonic saline

OBJECTIVE: Pulmonary edema is a serious condition following brain injury of diverse etiologies, including large hemispheric infarctions. We have previously shown that treatment with hypertonic saline attenuates cerebral edema associated with experimental ischemic stroke. In a well-characterized animal model of large ischemic stroke, we tested the hypotheses that lung water increases following cerebral ischemia and determined the effects of osmotherapy with hypertonic saline and mannitol on total lung water, as well as on cerebral edema. DESIGN: Prospective laboratory animal study. SETTING: Research laboratory in a university teaching hospital. SUBJECTS: Adult male Wistar rats (300-450 g, n = 103). INTERVENTIONS: Under controlled conditions of normoxia, normocarbia, and normothermia, spontaneously breathing, halothane-anesthetized (1.0-1.5%) rats were subjected to permanent middle cerebral artery occlusion by the intraluminal occlusion technique. MEASUREMENTS AND MAIN RESULTS: Cerebral perfusion was monitored by laser-Doppler flowmetry over ipsilateral parietal cortex to ensure adequate vascular occlusion. At 6 hrs following middle cerebral artery occlusion, rats were treated in a blinded randomized fashion with no intravenous fluids (n = 24), a continuous intravenous infusion (0.3 mL/hr) of 0.9% saline (n = 21), 20% mannitol (2 g/Kg) (n = 20), 5% hypertonic saline (n = 20), or 7.5% hypertonic saline (n = 18) as a chloride/acetate mixture (50:50) until the end of the experiment. Brains and lungs were harvested, and tissue water content was estimated by comparing wet-to-dry weight ratios of ipsilateral and contralateral cerebral hemispheres at 48 hrs postischemia. Sham-operated rats served as controls (n = 20). Serum osmolality was determined at the end of the experiment in all animals. Lung water content was increased significantly in rats subjected to middle cerebral artery occlusion and treated with no intravenous fluids (76.7 +/- 0.7%, 317 +/- 7 mOsm/L) (mean +/- sd) and saline (76.8 +/- 1.2%, 311 +/- 10 mOsm/L), compared with sham-operated controls (74.5 +/- 0.9%, 302 +/- 4 mOsm/L). Treatment with 20% mannitol (74.4 +/- 1.2%, 352 +/- 15 mOsm/L), 5% hypertonic saline (75.6 +/- 1.3%, 339 +/- 16 mOsm/L), and 7.5% hypertonic saline (74.9 +/- 0.7%, 360 +/- 23 mOsm/L) significantly attenuated lung water content. Hemispheric brain water content increased both in the ipsilateral ischemic and contralateral hemispheres treated with saline (ipsilateral, 85.1 +/- 1.7%; contralateral, 80.7 +/- 0.7%), compared with sham-operated controls (ipsilateral, 79.6 +/- 0.9%; contralateral, 79.5 +/- 0.9%), as well as in rats that received no fluids (ipsilateral, 84.6 +/- 1.8%; contralateral, 80.4 +/- 0.9%). Treatment with 5% hypertonic saline (ipsilateral, 83.8 +/- 1.0%; contralateral, 79.7 +/- 0.6%) and 7.5% hypertonic saline (ipsilateral, 82.3 +/- 1.3%; contralateral, 78.6 +/- 0.7%) resulted in attenuation of stroke-associated increases in brain water content to a greater extent than mannitol (ipsilateral, 83.6 +/- 1.6%; contralateral, 79.1 +/- 1.0%). CONCLUSIONS: In a well-characterized animal model of large ischemic stroke, total lung water content increases, which is likely neurogenic in origin. Attenuation of stroke-associated increases in lung and brain water content with continuous infusion of hypertonic saline may have therapeutic implication in the treatment of cerebral and pulmonary edema following ischemic stroke.     

Changes in atrial natriuretic peptide concentration and expression of its receptors after pneumonectomy in the rat

Atrial natriuretic peptide (ANP) is a cardiac hormone which affects endothelial cell function through a receptor-mediated process. Pneumonectomy is a common thoracic surgical procedure that can cause pulmonary oedema in the remaining lung. Few reports have investigated the aetiology of this complication. The aim of this study was to determine the changes in ANP concentration and expression of its receptors following pneumonectomy as a possible aetiology for postpneumonectomy pulmonary oedema (PPE). We compared plasma ANP concentrations, cGMP concentrations, and natriuretic peptide receptor (NPR)-A mRNA and NPR-C mRNA expression in rat lung 3 h after pneumonectomy (n=5) or a sham operation (n=5). The ANP concentrations in plasma and lung tissue in the pneumonectomy group were significantly higher than in the control group (749.5 versus 202.7 pg x ml(-1), P<0.01; 33.1 versus 6.8 ng x g(-1) wet tissue, P<0.01 respectively). The level of ANP mRNA expression in the pneumonectomy group was significantly higher than in the control group (1.44 versus 0.41 relative ANP mRNA expression, P<0.05). The concentration of cGMP and the level of NPR-A mRNA expression were not significantly different between the pneumonectomy and control groups. The level of NPR-C mRNA expression in the pneumonectomy group was significantly higher than in the control group (4.17 versus 2.19 relative NPR-C mRNA expression, P<0.01). These findings suggest that changes in pulmonary ANP and NPR-C expression may contribute to the development of PPE in the remaining lung in the acute phase following pneumonectomy.     

Extravascular lung water after pneumonectomy and one-lung ventilation in sheep

OBJECTIVE: To compare the single thermodilution and the thermal-dye dilution techniques with postmortem gravimetry for assessment of changes in extravascular lung water after pneumonectomy and to explore the evolution of edema after injurious ventilation of the left lung. DESIGN: Experimental study. SETTING: University laboratory. SUBJECTS: A total of 30 sheep weighing 35.6 +/- 4.6 kg. The study included two parts: a pneumonectomy study (n = 18) and an injurious ventilation study (n = 12). METHODS: Sheep were anesthetized and mechanically ventilated with an FiO2 of 0.5, tidal volume of 6 mL/kg, and positive end-expiratory pressure of 2 cm H2O. In the pneumonectomy study, sheep were assigned to right-sided pneumonectomy (n = 7), left-sided pneumonectomy (n = 7), or lateral thoracotomy only (sham operation, n = 4). In the injurious ventilation study, right-sided pneumonectomy was followed by ventilation with a tidal volume of 12 mL/kg and positive end-expiratory pressure of 0 cm H2O (n = 6) or by ventilation with a tidal volume of 6 mL/kg and positive end-expiratory pressure of 2 cm H2O for 4 hrs (n = 6). Volumetric variables, including extravascular lung water index (EVLWI), were measured with single thermodilution (STD; EVLWI(STD)) and thermal-dye dilution (TDD; EVLWI(TDD)) techniques. We monitored pulmonary hemodynamics and respiratory variables. After the sheep were killed, EVLWI was determined for each lung by gravimetry (EVLWI(G)). RESULTS: In total, the study yielded strong correlations of EVLWI(STD) and EVLWI(TDD) with EVLWI(G) (n = 30; r = .83 and .94, respectively; p < .0001). After pneumonectomy, both the left- and the right-sided pneumonectomy groups displayed significant decreases in EVLWI(STD) and EVLWI(TDD). The injuriously ventilated sheep demonstrated significant increases in EVLWI that were detected by both techniques. The mean biases (+/-2 SD) compared with EVLWI(G) were 3.0 +/- 2.6 mL/kg for EVLWI(STD) and 0.4 +/- 1.6 mL/kg for EVLWI(TDD). CONCLUSIONS: After pneumonectomy and injurious ventilation of the left lung, TDD and STD displayed changes in extravascular lung water with acceptable accuracy when compared with postmortem gravimetry. Ventilator-induced lung injury seems to be a crucial mechanism of pulmonary edema after pneumonectomy.     

Distribution of Pneumocystis jirovecii in lungs from colonized COPD patients

Pneumocystis jirovecii has been detected in lung tissue from patients with chronic obstructive pulmonary disease (COPD) and is associated with disease severity. The regional distribution of the organism in lungs is unknown, but differences in distribution of Pneumocystis could affect estimates of colonization prevalence. We examined the distribution of Pneumocystis in the lungs of 19 non-HIV-infected patients with COPD who were undergoing lung transplantation. DNA was extracted from explanted lungs. We found Pneumocystis colonization in lung tissue of 42.1% of patients with advanced COPD; however, there was significant regional variation in colonization between lung segments of individual patients. Colonization was detected more commonly in the lower and middle lobes than in the upper lobes. These findings suggest that single samples from an individual may underestimate the prevalence of Pneumocystis colonization and future studies may obtain a higher yield of Pneumocystis colonization detection when sampling the lower lobes.     

Intraamniotic interleukin-1 accelerates surfactant protein synthesis in fetal rabbits and improves lung stability after premature birth.

Intraamniotic infection is associated with increased IL-1 activity in amniotic fluid, increased incidence of preterm labor, and with decreased incidence of respiratory distress syndrome in infants born prematurely. We hypothesized that an elevated IL-1 in amniotic fluid promotes fetal lung maturation. On day 23 or 25 of gestation (term 31 d), either IL-1alpha (150 or 1,500 ng per fetus) or its antagonist IL-1 receptor antagonist (IL-1ra, 20 microg) was injected to the amniotic fluid sacs in one uterine horn, whereas the contralateral amniotic sacs were injected with vehicle. Within 40 h, IL-1alpha caused a dose-dependent increase in surfactant protein-A (SP-A) and SP-B mRNAs (maximally, fivefold), without affecting lung growth or increasing inflammatory cells in the lung. Both genders, and upper and lower lung lobes were similarly affected. IL-1ra did not modify SP-A, -B, or -C mRNA. IL-1 increased the intensity of staining of alveolar type II cells for SP-B, and the concentrations of SP-B, -A, and disaturated phosphatidylcholine in bronchoalveolar lavage. The dynamic lung compliance and the postventilatory expansion of lungs were increased two- to fourfold after IL-1alpha treatment. In fetal lung explants, IL-1alpha increased the expression of SP-A mRNA. IL-1 in amniotic fluid in preterm labor may promote lung maturation and thus be part of a host-defense mechanism that prepares the fetus for extrauterine life.     

VAMT肺切除术51例

目的:探讨电视胸腔镜辅助小切口(VAMT)在各式肺切除术的可行性、适应证和意义。方法:应用VAMT肺切除术治疗肺部良性病变和肺癌51例,采用常规开胸手术器械与内镜器械相结合直视操作行全肺切除、肺叶切除及病变局部切除术。结果:51例VAMT肺切除术顺利完成,平均手术时间80 min,平均住院时间9d,无死亡,术后并发症少。结论:VAMT可有选择地应用于除袖式肺叶切除术以外的多种肺切除术,适合于肺部良性病变、转移性肺癌及部分原发性肺癌病人的手术治疗,适应证广,具有创伤小、疼痛轻、恢复快、切口美观等优点,值得推广。     

Nerve constriction in the rat: model of neuropathic, surgical and central pain.

In preparation for a series of electrophysiological experiments in a model of neuropathic pain, the present spinal reflex study was done to determine the optimal time after sciatic nerve constriction in the rat for tactile allodynia and to determine also the appropriate 'control' for the nerve constriction model. Therefore, this study focused on the magnitude and time course of change in paw withdrawal threshold following unilateral sciatic nerve constriction in the rat. Male Sprague-Dawley rats (375-425g) were used. Nerve constriction was done by placing a 2 mm polyethylene cuff (PE-90) around the left sciatic nerve (n=8). A second group of rats (n=8) received unilateral sham surgery and a third group (n=8) was unoperated. The ipsi- and contralateral hind paw withdrawal thresholds in each of the 3 groups were measured using von Frey hairs. In unoperated rats, the withdrawal threshold of each of the hind paws remained unchanged at approximately 50 g throughout the entire time course of the study, which lasted 145 days. However, in cuff-implanted rats, the withdrawal threshold of the nerve-injured hind paw decreased as soon as 1 day after surgery, reached as low as 1 to 2 g by 5 days and remained low throughout the test period. Threshold in sham-operated rats showed a bilateral decrease starting on days 1-3, which stabilised at about 30 g until about day 40, after which values returned gradually toward the unoperated withdrawal thresholds. In nerve-constricted rats the withdrawal threshold of the hind paw contralateral to the cuff followed the same change seen in sham-operated rats until about day 37, after which the withdrawal threshold matched that of the cuff-implanted hind paw. The data show that the cuff-induced sciatic nerve constriction produces a sustained hypersensitivity to normally innocuous tactile sensory input and that a relatively constant ipsilateral mechanical hyperalgesia can be found from days 5-27. It is also demonstrated that the contralateral hind paw and either hind paw in sham-operated rats are inappropriate as 'controls'. The data in this study suggest that three distinct types of allodynia are expressed. Ipsilateral allodynia may be representative of a model of neuropathic pain. The contralateral allodynia may be a model of central pain, as it likely arises from changes in central sensory processing. Allodynia in sham-operated rats was also expressed bilaterally and may be a model of long-term postoperative pain.     

Glutamine metabolism in the lungs of glucocorticoid-treated rats.

1. The effect of dexamethasone (30 micrograms day-1 100 g-1 body weight) on the regulation of glutamine metabolism was studied in the lungs of rats after 9 days of treatment. 2. Dexamethasone resulted in a negative nitrogen balance, and produced decreases in the blood concentrations of glutamine (32.3%) and glutamate (25.3%) but an increase in the blood concentration of alanine (33.9%). 3. Dexamethasone treatment increases the rates of production of glutamine and alanine by lung slices incubated in vitro. 4. Blood flow and arteriovenous concentration difference measurement across the lungs exhibited an increase in the net exchange rates of glutamine (131.6%) and alanine (113.2%) in dexamethasone-treated rats compared with corresponding pair-fed controls. 5. Dexamethasone treatment produced significant decreases in the lung concentrations of glutamine (47.2%), glutamate (30.9%) and 2-oxoglutarate (57.3%). The concentrations of alanine (52.1%), ammonia (24.7%) and pyruvate (43.7%) were increased. 6. The maximal activity of glutamine synthetase was increased (21.5%), but there was no marked change in that of glutaminase, in the lungs of dexamethasone-treated rats. 7. It is concluded that glucocorticoid administration enhances the rates of production of glutamine and alanine from lungs of rats (both in vitro and in vivo). This may be due to changes in efflux and/or increased intracellular biosynthesis of glutamine and alanine.     

Cyclooxygenase inhibition in lungs or in neutrophils attenuates neutrophil-dependent edema in rat lungs perfused with phorbol myristate acetate

Results from previous studies indicate that injury in isolated rat lungs perfused with buffer containing phorbol myristate acetate (PMA) and rat neutrophils (PMNs) is dependent on the production of reactive oxygen species and thromboxane (Tx) A2. The purpose of this study was to determine whether the lung or the PMN was the source of TxA2 required to produce lung injury in this model. Prostanoid synthesis by rat lungs or PMNs was inhibited selectively by pretreatment of either rats or isolated PMNs with aspirin (100 mg/kg p.o. or 100 microM, respectively). Unbound aspirin was removed from the lungs and PMNs before use in experiments. Lungs from vehicle-pretreated rats that were perfused with PMA and untreated PMNs exhibited increases in weight, lavage fluid albumin content and TxB2 production with respect to lungs perfused with PMA but no PMNs. Increases in these markers were prevented when cyclooxygenase from either the lungs or the PMNs was inhibited. These results indicate that TxA2 is produced by both PMNs and by lung cells in this preparation, and that TxA2 production by both of these sources is required for the manifestation of edema.     

Effects of antibiotic therapy on Pseudomonas aeruginosa-induced lung injury in a rat model.

The effect of antibiotics on the acute lung injury induced by virulent Pseudomonas aeruginosa PA103 was quantitatively analyzed in a rat model. Lung injury was induced by the instillation of PA103 directly into the right lower lobes of the lungs of anesthetized rats. The alveolar epithelial injury, extravascular lung water, and total plasma equivalents were measured as separate, independent parameters of acute lung injury. Four hours after the instillation of PA103, all the parameters were increased linearly depending on the dose of P. aeruginosa. Next, we examined the effects of intravenously administered antibiotics on the parameters of acute lung injury in D-galactosamine-sensitized rats. One hour after the rats received 10(7) CFU of PA103, an intravenous bolus injection of aztreonam (60 mg/kg) or imipenem-cilastatin (30 mg/kg) was administered. Despite an MIC indicating resistance, imipenem-cilastatin improved all the measurements of lung injury; in contrast, aztreonam, which had an MIC indicating sensitivity, did not improve any of the lung injury parameters. The antibiotics did not generate different quantities of plasma endotoxin; therefore, endotoxin did not appear to explain the differences in lung injury. This in vivo model is useful to quantitatively compare the efficacies of parenteral antibiotic administration on Pseudomonas airspace infections.     

Effects of polyethylene glycol-linked superoxide dismutase and catalase during in vivo lung ischemia and reperfusion

We have previously demonstrated that reperfusion of a rabbit lung following 24 hours of in vivo pulmonary artery occlusion results in bilateral lung edema and lung inflammation and in systemic leukopenia. We tested whether this in vivo ischemia/reperfusion lung injury in the rabbit could be prevented by the administration of superoxide dismutase (SOD) and catalase (CAT). Polyethylene glycol-linked SOD (PEG-SOD) and CAT (PEG-CAT) were administered to five rabbits, PEG-SOD alone to four rabbits, and neither to nine untreated control rabbits, and the left pulmonary artery was then occluded with a microvascular clamp. Enzyme activity measured at the time of reperfusion 24 hours later demonstrated plasma CAT activity of 1,127 ± 601 U/mL for SOD/CAT-treated rabbits versus 193 ± 25 U / mL for untreated rabbits (P < .05) and SOD activity of 97 ± 25 U/mLfor SOD-treated rabbits versus no measurable activity in untreated rabbits. Following 4 hours of reperfusion, wet to dry ratios were 6.15 ± 0.27 for the reperfused left lungs and 5.55 ± 0.20 for the right lungs. Analysis of variance demonstrated a significant effect of reperfusion on left versus right wet to dry ratios (P < .05) but no effect of enzyme treatment. Lung sections scored by a blinded observer for histologic evidence of lung injury similarly showed a left-to-right difference but no difference between treated and untreated animals in degree of injury to the reperfused left lung. However, the contralateral lung was relatively less injured in treated rabbits. The two groups also differed in that an immediate leukopenia developed following reperfusion in the untreated and PEG-SOD-treated rabbits but not in the rabbits treated with both PEG-SOD and PEG-CAT. We conclude that SOD and CAT prevent the systemic leukopenia that accompanies pulmonary artery reperfusion, but do not prevent the injury to the reperfused lung. The sparing effect on the contralateral lung suggests that the mechanism of injury for that lung differs from the mechanism of injury to the occluded lung.     

Mediastinoscopic salvage esophagectomy for recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy in a previously pneumonectomized patient

We herein report a case of mediastinoscopic salvage esophagectomy for recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy in a previously pneumonectomized patient. A 66‐year‐old man with a medical history of left‐sided pneumonectomy for lung cancer was diagnosed with local recurrence of lower esophageal squamous cell carcinoma (cT3N0M0 cStage II) 9 years after definitive chemoradiotherapy. The mediastinoscopic cervical approach and laparoscopic transhiatal approach were combined, and the thoracic esophagus was safely mobilized to separate the esophagus from the stump of the left bronchus and to divide dense adhesions between the esophagus and fibrotic tissue at the site of the previous left mediastinal pleural resection. The esophagectomy was uneventful and followed by reconstruction with a gastric conduit via the retrosternal route. The pathological diagnosis was esophageal squamous cell carcinoma (pT3‐AD, pN1, M0, pStage III), indicating R0 resection. Even as salvage surgery, mediastinoscopic esophagectomy is a safe and curative treatment strategy for esophageal cancer patients who have previously undergone pneumonectomy.     

早产鼠高氧肺损伤中肺表面活性物质的代谢变化

目的：探讨早产鼠高氧肺损伤对其肺表面活性物质蛋白（SP）基因表达及肺表面活性物质（PS）代谢的影响。方法：孕21日SD早产鼠仔96只被随机分为高氧暴露组（48只,常压高氧舱中,氧体积分数＞0．95）和空气对照组（48只,正常空气中）,高氧暴露7日后,采用逆转录－聚合酶链反应（RT－PCR）和双相薄层层析法（2D－TLC）观察了8只鼠肺SP mRNA水平和PS含量;对20只鼠肺支气管肺泡灌洗液（BALF）肺组织干重／湿重和10只鼠肺组织学变化也进行了分析。结果：与空气对照组比较,高氧暴露组发展为肺损伤,肺组织有明显水肿、出血;BALF中蛋白含量、细胞数和肺组织干重／湿重明显增加（P均＜0．05）,而PS含量未见明显变化（P均＞0．05）。SP－A mRNA和SP－BmRNA增加（P均＜0．05）,SP－C mRNA变化未达统计学意义（P＞0．05）。结论：早产鼠早期高氧肺损伤并不明显影响PS含量的变化,但可导致SP－A mRNA和SP－B mRNA增加,这种基因表达的向上调节可能是机体的一种保护性应激反应。     

Regional distribution of gas and tissue in acute respiratory distress syndrome. I. Consequences for lung morphology

Objective: To compare the computed tomographic (CT) analysis of the distribution of gas and tissue in the lungs of patients with ARDS with that in healthy volunteers. Design: Prospective study over a 53-month period.¶Setting: Fourteen-bed surgical intensive care unit of a university hospital. Patients and participants: Seventy-one consecutive patients with early ARDS and 11 healthy volunteers. Measurements and results: A lung CT was performed at end-expiration in patients with ARDS (at zero PEEP) and healthy volunteers. In patients with ARDS, end-expiratory lung volume (gas + tissue) and functional residual capacity (FRC) were reduced by 17 % and 58 % respectively, and an excess lung tissue of 701 ± 321 ml was observed. The loss of gas was more pronounced in the lower than in the upper lobes. The lower lobes of 27 % of the patients were characterized by “compression atelectasis,” defined as a massive loss of aeration with no concomitant excess in lung tissue, and “inflammatory atelectasis,” defined as a massive loss of aeration associated with an excess lung tissue, was observed in 73 % of the patients. Three groups of patients were differentiated according to the appearance of their CT: 23 % had diffuse attenuations evenly distributed in the two lungs, 36 % had lobar attenuations predominating in the lower lobes, and 41 % had patchy attenuations unevenly distributed in the two lungs. The three groups were similar regarding excess lung tissue in the upper and lower lobes and reduction in FRC in the lower lobes. In contrast, the FRC of the upper lobes was markedly lower in patients with diffuse or patchy attenuations than in healthy volunteers or patients with lobar attenuations. Conclusions: These results demonstrate that striking differences in lung morphology, corresponding to different distributions of gas within the lungs, are observed in patients whose respiratory condition fulfills the definition criteria of ARDS.     

Hepatic adenine nucleotides and microsomal cholesterol 7α-hydroxylase activity in the obstructed and freely draining lobes of the liver after selective bile duct obstruction

Background The effect of selective bile duct obstruction (SBDO) on hepatic reserve function of the bile duct obstructed (BDO) and nonobstructed freely draining (FD) lobes of the liver is obscure. Methods The bile duct branches draining from the left lateral and median lobes of the liver were ligated for 4 and 10 days in rats, and hepatic reserve functions in BDO and FD lobes were assessed by microsomal cholesterol 7α-hydroxylase activities and by hepatic adenine nucleotide and energy charge levels. The values were com-pared with those in sham-operated control liver. Cholesterol 7α-hydroxylase activities were determined by gas-liquid chromatography-mass spectrometry, and hepatic adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels with high-pressure liquid chromatography. Results The histological examination of the BDO lobes showed proliferation and formation of new bile ductules and fibrous connective tissue linking portal areas. Microsomal cholesterol 7α-hydroxylase activities, hepatic energy charge and adenine nucleotide levels did not differ between FD and BDO lobes, and the values were similar to those in the sham-operated liver. Conclusions Selective bile duct obstruction shows no adverse effects on microsomal and mitochondrial functions in either BDO or FD lobes of the liver.     

重组葡激酶对重症急性胰腺炎大鼠胰腺组织缺血的影响

目的观察大鼠重症急性胰腺炎（SAP）时血中内皮素-1（ET-1）、血管性假血友病因子（vWF）、6-酮-前列腺素-F1α（6-keto-PGF1α）、血栓素B2（TXB2）、血小板最大聚集率（PAGm）水平及胰腺组织血流量的变化，评价重组葡激酶（r—Sak）对其的干预作用。方法81只SD大鼠被随机分为假手术组、SAP模型组和r—Sak治疗组，每组27只。采用质量分数为5％的牛磺胆酸钠胰胆管逆行注射方法建立SAP模型。于制模后6、12和18h检测下列指标：用组织血流仪检测胰腺组织的血流量；用放射免疫法检测血中ET-1、TXB2和6-keto-PGF1α含量；用双抗体夹心酶联免疫吸附法（ELISA）测定血中vWF含量；用全自动血小板聚集仪检测胶原和花生四烯酸诱导的PAGm。结果术后6、12和18h SAP模型组大鼠胰腺组织血流量呈逐渐下降趋势，各时间点胰腺组织血流量均较假手术组显著下降（P均〈0．05），且术后各时间点PAGm及血中ET-1、vWF、TXB2含量均较假手术组显著升高，6-keto-PGF1α显著降低（P均〈0.05）；与SAP模型组比较，r—Sak治疗组术后各时间点PAGm、ET-1、vWF、TXB2含量均显著降低，6-keto-PGF1α则显著升高（P均〈0.05）。结论r—Sak可明显改善SAP大鼠胰腺的微循环，增加胰腺组织的血流量，对SAP大鼠具有积极的治疗作用。     

Depletion of OX-8 lymphocytes from the blood and airways using monoclonal antibodies enhances the late airway response in rats.

Recent evidence supports a role for T lymphocytes in allergic airway responses. We hypothesized that reducing blood T suppressor cells (Ts) might increase the late airway response (LR). Sprague-Dawley (SD) rats were sensitized with ovalbumin (OA). On days 8, 10, and 12, post-sensitization test SD (n = 14) received monoclonal antibody intravenously (OX-8; 1 mg) specific to rat Ts. Controls received saline (n = 7) or mouse ascites IgG (n = 7). On day 14, animals were challenged with OA aerosol (5% wt/vol) for 5 min, lung resistance was recorded for 8 h (n = 18) and bronchoalveolar lavage was performed. The LR was determined from the area under the lung resistance vs time curve from 75 to 480 min after challenge. In the remaining 10 rats, airway lymphocyte subsets were measured 8 h after OA aerosol challenge in minced and digested lungs. A decrease in percentage of blood and airway Ts, respectively, in test animals was observed vs controls (blood: 6.27 +/- 0.84 vs 32.95 +/- 1.94, P < 0.001); (airway: 5.05 +/- 0.66 vs 24.5 +/- 3.05, P < 0.02). Blood and airway helper T lymphocytes did not differ between test and control animals. The LR was significantly increased in test (22.89 +/- 3.92) vs controls (4.22 +/- 2.18, P < 0.001). Bronchoalveolar lavage macrophages, neutrophils and lymphocytes, and serum OA-specific IgE were also significantly elevated (P < 0.05) in test animals. We conclude that Ts play an important role in attenuating the LR in SD rats.     

SPN的CT强化效应与鉴别诊断:不强化肺癌的病理因素分析

目的探讨在增强CT扫描中肺癌不强化的病理因素。方法回顾性分析32例不强化肺癌患者的术前CT和术后病理，男性27人。女性5人；年龄在46～74岁，中位年龄57岁。CT检查采用病灶中心层面同床位增强前后动态扫描，依据定位片上病灶的大小决定层厚和层距(2～10mm)。使用非离子型对比剂优维显80—100ml(300mg/ml)，压力注射器给予，流率为2～3ml／s。测量注射对比剂前和注射后即刻、1分钟、2分钟、3分钟时病灶同一位置CT值，以两者之差≥30Hu作为病灶有强化的下限：手术标本先裸眼解剖观察，然后用石蜡包埋切片、H—E染色或／和免疫组化染色观察，获得组织学诊断。结果病灶位于两肺上叶者11例．右肺中叶者6例，两肺下叶者15例。病灶长径在18—56mm之间，平均37mm。病理组织分型中鳞癌19例，腺癌5例，腺鳞癌2例，大细胞未分化癌4例．肺泡细胞癌2例。增强扫描CT强化值在29—213Hu间者17例。19—10Hu间者11例，9Hu以下者4例。结论增强CT扫描中肺癌不强化主要与病灶大小和组织类型有关，多见于癌灶大于3cm者和鳞癌、大细胞未分化癌及腺癌(包括肺泡细胞癌)。     

Glutamine and alanine metabolism in lungs of septic rats.

1. The metabolism of glutamine and alanine in the lung was studied in rats made septic by a caecal ligation and puncture technique. 2. The blood glucose concentration was not significantly different in septic rats, but blood pyruvate, lactate, glutamine and alanine concentrations were markedly increased as compared with sham-operated rats. Conversely, blood ketone body and plasma cholesterol concentrations were significantly decreased in septic rats. Both plasma insulin and plasma glucagon concentrations were markedly elevated in response to sepsis. Sepsis resulted in a negative nitrogen balance. 3. Sepsis increased the rates of production of glutamine (52.5%, P less than 0.001), alanine (38.9%, P less than 0.001) and glutamate (48.6%, P less than 0.001) by lung slices incubated in vitro. 4. Sepsis increased lung blood flow by 27.6% (P less than 0.05). Blood flow and arteriovenous concentration difference measurement across the lung of septic rats showed an increase in the net exchange rates of glutamine (142.5%, P less than 0.001), alanine (129.4%, P less than 0.001), glutamate (100.9%, P less than 0.001) and ammonia (138.0%, P less than 0.001) as compared with sham-operated control rats. 5. Sepsis produced significant decreases in the lung concentrations of glutamine (36.8%), glutamate (20.8%), 2-oxoglutarate (64.8%) and AMP (18.3%). The lung concentrations of alanine (95.9%), ammonia (67.7%) and pyruvate (89.7%) were increased. 6. The maximal activities of glutamine synthetase (20.4%, P less than 0.05), phosphate-dependent glutaminase (18.9%, P less than 0.05) and alanine aminotransferase (25.5%, P less than 0.05) were increased, but there was no marked change in that of glutamate dehydrogenase, in the lungs of septic rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic adenine nucleotides and microsomal cholesterol 7α-hydroxylase activity in the obstructed and freely draining lobes of the liver after selective bile duct obstruction

Background: The effect of selective bile duct obstruction (SBDO) on hepatic reserve function of the bile duct obstructed (BDO) and nonobstructed freely draining (FD) lobes of the liver is obscure.Methods: The bile duct branches draining from the left lateral and median lobes of the liver were ligated for 4 and 10 days in rats, and hepatic reserve functions in BDO and FD lobes were assessed by microsomal cholesterol 7α-hydroxylase activities and by hepatic adenine nucleotides and energy charge levels. The values were compared with those in the sham-operated control liver. Cholesterol 7α-hydroxylase activities were determined by gas-liquid chromatography-mass spectrometry, and hepatic adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels with high-pressure liquid chromatography.Results: The histological examination of the BDO lobes showed proliferation and formation of new bile ductules and fibrous connective tissues linking portal areas. Microsomal cholesterol 7α-hydroxylase activities, hepatic energy charge and each adenine nucleotide level did not differ between FD and BDO lobes, and the values were similar to those in the sham-operated liver.Conclusions: Selective bile duct obstruction shows no adverse effects on microsomal and mitochondrial functions in both the BDO and FD lobes of the liver.