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.     

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)。     

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.     

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.     

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。     

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。     

Effect of antihypertensive treatment on the left ventricular isomyosin profile in one-clip, two kidney hypertensive rats

In order to investigate the cardiac effects of antihypertensive therapies in one-clip two-kidney hypertension in rats, we compared the consequences on myosin isoenzyme profile and on left ventricular hypertrophy of two treatments: one was a new converting enzyme inhibitor (S9490), the second a more standard tripletherapy associating clonidine, dihydralazine and furosemide. The two treatments were initiated 4 weeks after clipping and administered during 5 weeks. During the treatment period average systolic blood pressure was 215 +/- 32 mmHg in the hypertensive untreated group (HC2, n = 12) and 144 +/- 13 mm Hg in the CEI group (HT1, n = 13), which is not significantly different from the value found in the sham-operated group (139 +/- 4 mm Hg, C2, n = 13). Blood pressure was lowered only to 173 +/- 18 mm Hg in the group treated with tripletherapy (HT2, n = 12). The left ventricular weight decreased significantly in the CEI-treated group toward values similar to those of the sham-operated animals (2.2 +/- 0.13 mg/g vs. 1.9 +/- 10 mg/g, respectively NS), whereas it did not change in the tripletherapy group when compared to the untreated hypertensive animals despite the fall in blood pressure. In the hypertensive untreated rats the percentage of V1 isoenzyme of cardiac myosin was lower than in the sham-operated group (42.8 +/- 9.0% vs. 57.5 +/- 7.6% P less than .001). In parallel the V3 form of cardiac myosin increased (24.1 +/- 7.4% vs. 15.7 +/- 4.3%, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Beneficial effect of methylprednisolone on cardiac myocytes in a rat model of severe brain injury

Cardiac injury, occurred after traumatic brain injury (TBI), has been recognized for more than a century. Bcl-2 is a key regulatory component of the mitochondrial cell death pathway, and its overexpression is cytoprotective in many cell types. The therapeutic agents, which induce the expression of bcl-2 protein, might provide a new therapy to prevent cardiac myocyte damage following TBI. In this study, we investigated whether methylprednisolone sodium succinate (MPSS) influences the expression of bcl-2 in the heart. Wistar-Albino female rats underwent TBI (300 g/cm) generated by the weight-drop method, and were left untreated (n = 6) or treated with either MPSS (30 mg/kg) (n = 6) or vehicle (albumin solution) (n = 6). The heart was isolated from each animal with TBI. For comparison, the hearts were isolated from sham-operated (n = 6) and control rats (n = 6). The relative expression of bcl-2 mRNA in the heart was quantitated by real-time polymerase chain reaction. We also assessed lipid peroxidation in the heart tissue by determining the concentration of thiobarbituric acid-reactive substances (TBARs) as an indicator of tissue damage. The bcl-2 expression level was significantly higher in the hearts of MPSS-treated rats compared to that of other TBI groups (p < 0.0001). Moreover, TBI increased the lipid peroxidation in the heart, which was significantly reduced by the treatment with MPSS (p < 0.0001). These findings provide evidence for the efficacy of MPSS in protection of cardiac myocytes to achieve optimal heart donation after TBI in heart transplantation.     

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.     

Evidence for lipid peroxidation by paraquat in the perfused rat lung

In order to evaluate the effect of paraquat on oxidative radical reactions in the lung, we studied MDA production and chemiluminescence (spontaneous and tBuOOH-induced) in the isolated rat lung. After 2 hr of perfusion with 3.0 mM paraquat, MDA content in lung homogenates was 16 +/- 7 nmol/gm dry weight higher than in control lungs (mean +/- S.E., n = 7, p less than 0.05 by paired test); during 30 min of perfusion, malondialdehyde efflux was 33 +/- 15 nmol/gm dry weight higher than in control perfusates (n = 6, p less than 0.05). Spontaneous chemiluminescence was not augmented by 2 hr of perfusion with concentrations of paraquat ranging from 0.75 to 6.0 mM. On the other hand, tBuOOH-induced chemiluminescence was 17% +/- 3 higher immediately after the addition of hydroperoxide and reached a 16% +/- 6 higher plateau for the paraquat-perfused lungs than for control lungs (n = 10, p less than 0.05). Spectral analysis of the light emitted during induced chemiluminescence demonstrated peak intensity between 630 and 730 nm for both control and paraquat-treated lungs. Increased MDA production and increased induced chemiluminescence indicate that perfusion with paraquat enhances lipid peroxidation in the isolated rat lung.     

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 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.     

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.     

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.     

A rat model of acute lung injury induced by cardiopulmonary bypass.

Impaired lung function is still a major complication after cardiac surgery with cardiopulmonary bypass. The purpose of the present study was to develop an experimental model of acute pulmonary injury induced by cardiopulmonary bypass in Wistar rats. Cardiopulmonary bypass was performed for 60 min using a non-pulsatile roller pump and a membrane oxygenator (n = 8 for cardiopulmonary bypass group and n = 7 for control rats). We measured tracheal pressure, airflow, and lung volume changes and obtained pulmonary resistance and dynamic elastance. After the cardiopulmonary bypass, lungs were submitted to a quick-freezing protocol and morphometric analysis was performed. There was a time-dependent increase in dynamic elastance, but not pulmonary resistance, only in the rats submitted to cardiopulmonary bypass (P = 0.005). Lungs from animals submitted to cardiopulmonary bypass showed significantly more alveolar hemorrhage (P = 0.025) and edema (P = 0.021), as well as perivascular edema (P = 0.003) when compared to control rats. In our experimental model, rats submitted to cardiopulmonary bypass developed acute pulmonary changes similar to the early phase of acute pulmonary distress syndrome. Cardiopulmonary bypass resulted in an increase in pulmonary elastance without changes in resistance. This experimental model is suitable for studies concerning the mechanisms of acute lung injury induced by cardiopulmonary bypass.     

内膜新生性肺血管重构肺动脉高压大鼠模型的建立及评价

背景：目前尚缺乏简单易行、实用、操作性强的血管内膜新生性肺血管重构肺动脉高压动物模型。目的：建立内膜新生性肺血管重构大鼠肺动脉高压模型。方法：40只雄性SD大鼠随机分为2组：M＋P组（n=26）大鼠行左肺切除,2周后皮下注射野百合碱60mg/kg;对照组（n=14）大鼠仅行假手术处理。于术后5周检测肺动脉压、右心室/（左心室＋室间隔）质量的比值,同时观察右肺动脉病理形态学改变。以光镜下每1mm2面积内Ⅷ因子标记阳性的直径小于100μm的肺血管数评价肺内微血管密度。结果与结论：M＋P组大鼠存活率85%（22/26）,对照组存活率为100%（14/14）。与对照组相比,M＋P组大鼠肺动脉压力和右心室/（左心室＋室间隔）质量的比值明显增高（P〈0.01）;与对照组相比,M＋P组大鼠肺内直径为50-100μm和100-150μm的肌型小动脉中膜相对厚度均显著增加（P〈0.01）,肺内微血管密度显著减少（P〈0.01）。光镜显示M＋P组大鼠注射野百合碱后5周肌型肺小动脉中膜明显增厚,肺腺泡内小动脉明显肌化、内膜增厚。对照组大鼠肺小动脉未见血管结构重建。实验成功建立了内膜新生性肺血管重构大鼠肺动脉高压模型,操作相时简便,动物死亡率较低。     

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.     

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.