Lung and vascular function during chronic severe pulmonary ischemia

Bronchial vascular angiogenesis takes place in a variety of lung inflammatory conditions such as asthma, cystic fibrosis, lung cancer, and chronic pulmonary thromboembolic disease. However, it is unclear whether neovascularization is predominantly appropriate and preserves lung tissue or whether it contributes further to lung pathology through edema formation and inflammation. In the present study we examined airway and lung parenchymal function 14 days after left pulmonary artery ligation. In rats as well as higher mammals, severe pulmonary ischemia results in bronchial vascular proliferation. Using labeled microspheres, we demonstrated an 18-fold increase in systemic blood flow to the ischemic left lung. Additionally, vascular remodeling extended to the tracheal venules, which showed an average 28% increase in venular diameter. Despite this increase in vascularity, airways resistance was not altered nor was methacholine responsiveness. Since these measurements include the entire lung, we suggest that the normal right lung, which represented 78% of the total lung, obscured the ability to detect a change. When functional indexes such as diffusing capacity, in situ lung volume, and vascular permeability of the left lung could be separated from right lung, significant changes were observed. Thus when comparing average left lung values of rats 14 days after left pulmonary artery ligation to left lungs of rats undergoing sham surgery, diffusing capacity of the left lung decreased by 72%, left lung volume decreased by 38%, and the vascular permeability to protein increased by 58%. No significant differences in inflammatory cell recruitment were observed, suggesting that acute ischemic inflammation had resolved. We conclude that despite the preservation of lung tissue, the proliferating bronchial neovasculature may contribute to a sustained decrement in pulmonary function.     

Mediastinal pancreatic pseudocyst--a case report and review of the literature

Pancreatic pseudocyst, a common complication of acute or chronic pancreatitis, in rare instances may also extend to the mediastinum. A case of 67-year-old woman presenting with a triad of chest pain, dysphagia, and dyspnea is presented. The patient had an episode of acute alcoholic pancreatitis 1 year before presentation. Chest radiography on admission showed a retrocardiac opacity. Two-dimensional echocardiography revealed an echolucent mass compressing the left atrium. A subsequent upper gastrointestinal series for her dysphagia showed extrinsic compression of the distal esophagus. Finally a definitive diagnosis was made with computed tomography (scan), which revealed a 19 x 12 cm pseudocyst extending from the body of pancreas into the thorax and compressing the esophagus and the cardiac chambers. A mediastinal pseudocyst can cause symptoms due to compression or invasion of surrounding structures. The fluid collection may enlarge slowly and hence the symptoms can be delayed as in our patient. The pseudocyst was successfully treated using endoscopic ultrasound-guided transesophageal drainage. Approximately 50 cases of mediastinal extension of the pancreatic pseudocyst in the world literature are reported. At this time, this is only the second time that successful drainage of a mediastinal pseudocyst using a transesophageal approach under endoscopic ultrasound guidance has been reported. The literature was reviewed for clinical presentation, complications, and available treatment options for mediastinal pancreatic pseudocysts.     

Evaluation of two-way protein fluxes across the alveolo-capillary membrane by scintigraphy in rats: effect of lung inflation.

Pulmonary microvascular and alveolar epithelial permeability were evaluated in vivo by scintigraphic imaging during lung distension. A zone of alveolar flooding was made by instilling a solution containing 99mTc-albumin in a bronchus. Alveolar epithelial permeability was estimated from the rate at which this tracer left the lungs. Microvascular permeability was simultaneously estimated measuring the accumulation of (111)In-transferrin in lungs. Four levels of lung distension (corresponding to 15, 20, 25, and 30 cmH2O end-inspiratory airway pressure) were studied during mechanical ventilation. Computed tomography scans showed that the zone of alveolar flooding underwent the same distension as the contralateral lung during inflation with gas. Increasing lung tissue stretch by ventilation at high airway pressure immediately increased microvascular, but also alveolar epithelial, permeability to proteins. The same end-inspiratory pressure threshold (between 20 and 25 cmH2O) was observed for epithelial and endothelial permeability changes, which corresponded to a tidal volume between 13.7 +/- 4.69 and 22.2 +/- 2.12 ml/kg body wt. Whereas protein flux from plasma to alveolar space ((111)In-transferrin lung-to-heart ratio slope) was constant over 120 min, the rate at which 99mTc-albumin left air spaces decreased with time. This pattern can be explained by changes in alveolar permeability with time or by a compartment model including an intermediate interstitial space.     

Double primary lung cancers: with special reference to their exfoliative cytology and to the rare, malignant "mixed" tumor of the salivary-gland type

Two autopsy cases are reported in which double primary cancers of the lung had been strongly or definitely suspected before death by demonstration of two different types of malignant cells in the sputum as well as in smears of aspirates from pleural fluid and/or mediastinal tumor. By exfoliative cytology, one case was characterized by carcinoma cells of the small-cell type plus the large-cell and/or adenocarcinoma type; the other displayed small-cell-type and squamous-cell-type malignant cells. The autopsies definitely revealed in the first case an anaplastic carcinoma of the small-cell type in the left bronchus and a salivary-gland-type malignant "mixed" tumor in the right lower lobe and in the second case an anaplastic carcinoma of the small-cell type in the right upper lobe and a squamous-cell carcinoma in the left upper lobe. The frequence of occurrence and pathologic diagnosis of double primary lung cancers are reviewed and discussed. A rare type of lung cancer, salivary-gland-type malignant "mixed" tumor, is given special reference.     

Giant cell carcinoma of the lung. Report of a case with cytohistologic and clinical correlation

BACKGROUND: Giant cell carcinoma (GCC) of the lung is an unusual tumor characterized by an aggressive outcome. CASE: A peripheral lung tumor was observed in an elderly male. At presentation the clinical symptoms were cough, thoracic pain and hemoptysis. Chest roentgenography showed a left pleural effusion and neutrophilia in the blood. Bronchoscopic examination showed a peripheral tumor mass that could not be biopsied. Bronchoalveolar lavage was negative. The patient underwent a cerebrovascular accident and died. The autopsy showed a peripheral giant cell tumor of the left lung that involved regional and mediastinal lymph nodes. Touch imprints showed tridimensional clusters of pleomorphic and large cells, some of which were multinucleated, containing leukocytes in their cytoplasm. CONCLUSION: This case illustrates the typical cytohistologic features of GCT of the lung, which should be considered in the differential diagnosis of any peripheral lung tumor composed of large cells. Clinical correlation is helpful in reaching the correct diagnosis.     

Effect of ischemia and reperfusion without airway occlusion on vascular barrier function in the in vivo mouse lung.

Ischemia-reperfusion (I/R) lung injury causes increased vascular permeability and edema. We developed an in vivo murine model of I/R allowing measurement of pulmonary vascular barrier function without airway occlusion. The left pulmonary artery (PA) was occluded with an exteriorized, slipknotted suture in anesthetized C57BL/6J mice. The effect of ischemic time was determined by subjecting mice to 5, 10, or 30 min of left lung ischemia followed by 150 min of reperfusion. The effect of reperfusion time was determined by subjecting mice to 30 min of left lung ischemia followed by 30 or 150 min of reperfusion. Changes in pulmonary vascular barrier function were measured with the Evans blue dye (EBD) technique, dual-isotope radiolabeled albumin (RA), bronchoalveolar lavage (BAL) protein concentration, and wet weight-to-dry weight ratio (WW/DW). Increasing left lung ischemia with constant reperfusion time or increasing left lung reperfusion time after constant ischemic time resulted in significant increases in left lung EBD content at all times compared with both right lung values and sham surgery mice. The effects of left lung ischemia on lung EBD were corroborated by RA but the effects of increasing reperfusion time differed, suggesting binding of EBD to lung tissue. An increase in WW/DW was only detected after 30 min of reperfusion, suggesting edema clearance. BAL protein concentrations were unaffected. We conclude that short periods of I/R, without airway occlusion, increase pulmonary vascular permeability in the in vivo mouse, providing a useful model to study molecular mechanisms of I/R lung injury.     

Effects of atropine on respiratory heat loss in asthma

We have previously observed that although atropine does not alter the magnitude of the response to exercise while breathing cold air, it does cause the predominant site of obstruction to move into the lung periphery. To determine if this effect was due to changes in the conditioning of inspired air, we measured respiratory heat loss (RHL) and retrotracheal (Trt) and retrocardiac esophageal temperature in eight asthmatics while they performed eucapnic hyperventilation with cold air before and after the inhalation of atropine. Multiple aspects of pulmonary mechanics were also recorded. Significant and equivalent airway obstruction developed with and without atropine (control delta FEV1 = 1.0 +/- 0.2 (SE) liter; postatropine = 0.9 +/- 0.3 liter). Despite this, RHL was 17.1% greater and Trt fell 16% more after atropine. These data demonstrate that atropine can influence heat transfer within the lung and alter the sites of conditioning.     

Autophagy decreases alveolar epithelial cell injury by regulating the release of inflammatory mediators

To research the impact of autophagy on alveolar epithelial cell inflammation and its possible mechanism in the early stages of hypoxia, we established a cell hypoxia–reoxygenation model and orthotopic left lung ischemia–reperfusion model. Rat alveolar epithelial cells stably expressing GFP-LC3 were treated with an autophagy inhibitor (3-MA) or an autophagy promoter (rapamycin), followed by hypoxia–reoxygenation treatment for 2, 4, and 6 hr in vitro. In vivo, 20 male Sprague Dawley rats were randomly divided into four groups (model group: No blocking of the hilum in the left lung; control group: Blocking of the hilum in the left lung for 1 hr with dimethyl sulfoxide lavage; 3-MA group: Blocking of the hilum in the left lung for 1 hr with 100 ml/kg of 3-MA (5 μmol/L) solution lavage; and rapamycin group: Blocking of the hilum in the left lung for 1 hr with 100 ml/kg of rapamycin (250 nmol/L) solution lavage) to establish an orthotopic left lung ischemia model. This study demonstrated that rapamycin significantly suppressed the nuclear factor kappa B signaling pathway and limited the expression of proinflammatory factors. A contrary result was found after the 3-MA pretreatment. These findings indicate that autophagy reduces ischemia–reperfusion injury by repressing inflammatory signaling pathways in the early stages of hypoxia in vitro and in vivo. Autophagy could be a new protective method for application in lung ischemia–reperfusion injury.     

A case of dextrocardia with normal situs.

We report here a case of dextrocardia with normal situs in an 81-year-old man who died from non-pulmonary causes. Removal of the chest wall revealed a large, but otherwise anatomically normal, left lung occupying the entire left hemithorax and extending across the midline to overlap the left border of the heart which was positioned in the right hemithorax. The gross anatomy of the heart was normal save its position and the presence of only 2 pulmonary veins. Dissection of the heart showed all chambers in their classically described position, and there were no valvular defects. The anatomy of the great vessels was also normal. The right lung was hypoplastic and lay posterior to the heart. This lung lacked any lobular structure, but the presence of carbon particles throughout it suggested that it was capable of normal inflation.     

Aerosolized Pseudomonas elastase and lung fluid balance in anesthetized sheep.

The role of the lung epithelium in lung fluid balance was studied by ventilating anesthetized sheep with an aerosol of 20 mg of elastase from Pseudomonas aeruginosa (Ps. elastase) to increase lung epithelial permeability without affecting lung endothelial permeability or lung vascular pressures. Ps. elastase had no effect on the lung vascular pressures, the alveolar-arterial PO2 gradient (A-aPO2), the flow or protein concentration of the lung lymph, or the postmortem water volume of the lungs. The morphological alveolar flooding score in these sheep was 2.5 times the control level, but this was only marginally significant. Elevation of the left atrial pressure by 20 cmH2O alone increased the postmortem lung water volume but had no effect on A-aPO2, the alveolar flooding score, or the lung epithelial permeability assessed by the clearance of 99mTc-labeled human serum albumin. Addition of aerosolized Ps. elastase to these sheep had no effect on the total lung water volume, but it caused a redistribution of water into the air spaces, as evidenced by significant increases in the alveolar flooding score and A-aPO2 (P less than 0.01). Elevation of the left atrial pressure by 40 cmH2O without elastase caused the same response as elevation of the left atrial pressure by 20 cmH2O with elastase, except the higher pressure caused a greater increase in the total lung water volume. We conclude that alteration of the integrity of the lung epithelium with aerosolized Ps. elastase causes a redistribution of lung water into the alveoli without affecting the total lung water volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of lung volume and alveolar pressure on reverse pulmonary venous blood flow.

We have reported that left atrial blood refluxes through the pulmonary veins to gas-exchanging tissue after pulmonary artery ligation. This reverse pulmonary venous flow (Qrpv) was observed only when lung volume was changed by ventilation. This was believed to drive Qrpv by alternately distending and compressing the alveolar and extra-alveolar vessels. Because lung and pulmonary vascular compliances change with lung volume, we studied the effect of positive end-expiratory pressure (PEEP) on the magnitude of Qrpv during constant-volume ventilation. In prone anesthetized goats (n = 8), using the right lung to maintain normal blood gases, we ligated the pulmonary and bronchial arterial inflow to the left lung and ventilated each lung separately. A solution of SF6, an inert gas, was infused into the left atrium. SF6 clearance from the left lung was determined by the Fick principle at 0, 5, 10, and 15 and again at 0 cmH2O PEEP and was used to measure Qrpv. Left atrial pressure remained nearly constant at 20 cmH2O because the increasing levels of PEEP were applied to the left lung only. Qrpv was three- to fourfold greater at 10 and 15 than at 0 cmH2O PEEP. At these higher levels of PEEP, there were greater excursions in alveolar pressure for the same ventilatory volume. We believe that larger excursions in transpulmonary pressure during tidal ventilation at higher levels of PEEP, which compressed alveolar vessels, resulted in the reflux of greater volumes of left atrial blood, through relatively noncompliant extra-alveolar veins into alveolar corner vessels, and more compliant extra-alveolar arteries.     

Cytokine mRNA expression in unilateral ischemic-reperfused rat lung with salt solution supplemented with low-endotoxin or standard bovine serum albumin

Our aim was to determine whether cytokine mRNA expression is induced by experimental manipulation including artificial perfusate or ischemia-reperfusion (I/R) in an isolated, perfused rat lung model. Constant pulmonary flow [Krebs-Henseleit solution supplemented with low-endotoxin (LE) or standard (ST) bovine serum albumin 4%, 0.04 ml/g body wt] and ventilation were maintained throughout. Right and left pulmonary arteries were isolated, and the left pulmonary artery was occluded for 60 min and then reperfused for 30 min. Analysis of tumor necrosis factor-alpha, IL-1 beta, IL-6, IL-10, and IFN-gamma mRNA expression by RT-PCR and evaluation of vascular permeability by bronchoalveolar lavage (BAL) fluid albumin content were conducted separately in right and left lung. Both LE and ST groups (each 12 rats) showed increases in vascular permeability by I/R (BAL fluid albumin content: 5.53 +/- 1.55 vs. 15.63 +/- 8.87 and 4.76 +/- 2.71 vs. 16.72 +/- 4.85 mg.ml BAL fluid-1.g lung dry wt-1, mean +/- SD; right vs. left lung in LE and ST groups, P < 0.05 between right and left). Cytokine mRNA expression was significantly higher in the I/R lung than in the control lung in the LE group, whereas it was higher in the control lung in the ST group (P < 0.05). mRNAs of not only proinflammatory but also anti-inflammatory cytokines were expressed in I/R lung, which are expected to aggravate I/R injury. The reversed pattern of cytokine mRNA expression in the ST group was possibly due to the longer perfusion of control lung with perfusate containing endotoxin, which caused no lung damage without I/R.     

Pulmonary vascular resistance after cessation of positive end-expiratory pressure

This report describes the pulmonary vascular response of infant lamb lung to abrupt cessation of positive end-expiratory pressure (PEEP) during volume-regulated continuous positive-pressure breathing (CPPB). In an intact, endobronchially ventilated preparation, the increase in left lung blood flow (QL) after abrupt cessation of 11 Torr left lung PEEP was found to be gradual, although peak airway pressure (Pmax) fell promptly from 36 to 14 Torr; 49% of the increase in QL occurred greater than 10 s after cessation of PEEP. Recruitment of zone I vasculature that had been created by balloon occlusion of the left pulmonary artery was found to occur promptly after balloon deflation. Isolated neonatal lamb lungs, perfused at constant flow rate, showed similar persistent elevation of pulmonary vascular resistance after cessation of 15 Torr PEEP, although Pmax fell abruptly from 39 to 12 Torr. This hysteresis was eliminated by calcium channel blockade with verapamil, and the magnitude of the change in pulmonary arterial pressure after either application or cessation of PEEP was reduced (25 and 26%, respectively). These observations suggest that, during CPPB, lung stretch alters neonatal pulmonary vascular tone or, by causing calcium channel-dependent lung volume hysteresis, modulates pulmonary vascular resistance. This interaction exaggerates the effect of airway pressure changes on pulmonary vascular resistance during mechanical ventilation.     

Lung ischemia-reperfusion injury in awake sheep: protection with verapamil.

We caused unilateral lung ischemia-reperfusion injury in awake sheep by simultaneously occluding the left pulmonary artery and left main stem bronchus for 12 h. The occluded left lung was inflated with nitrogen. Reperfusion resulted in an elevation of lung lymph flow from 1.3 to 5.0 ml/15 min and an increase in lymph-to-plsma protein concentration ratios. Reperfusion, but not ischemia alone, caused an increase in wet-to-dry weight ratios in both the reperfused left lung and the contralateral right lung. Granulocytes increased in both lungs during the ischemic period and after reperfusion, and hypoxemia developed after reperfusion. The calcium channel antagonist, verapamil, given just before reperfusion, caused a marked attenuation in the reperfusion-induced changes in the lung lymph variables and wet-to-dry weight ratio. However, verapamil did not affect the hypoxemia or granulocyte sequestration seen after reperfusion. We conclude that reperfusion of ischemic sheep lung results in increased microvascular permeability that can be partially prevented by verapamil.     

Distribution of the pulmonary artery and vein of the orangutan lung

The distribution of the pulmonary artery and vein of the orangutan lung was examined. The right pulmonary artery runs obliquely across the ventral side of the right bronchus at the caudally to the right upper lobe bronchiole. It then runs across the dorsal side of the right middle lobe bronchiole. Thereafter it runs obliquely across the dorsal side of the right bronchus, and then along the dorso-medial side of the right bronchus. This course is different from that in other mammals. During its course, it gives off branches which run mainly along the dorsal or lateral side of each bronchiole. The left pulmonary artery runs across the dorsal side of the left middle lobe bronchiole, then along the dorso-lateral side of the left bronchus, giving off branches which run along each bronchiole. The pulmonary veins run mainly the ventral or medial side of, along or between the bronchioles. In the left lung, the left middle lobe vein has two trunks; one enters the left atrium, and the other enters the left lower lobe pulmonary venous trunk. This is also different from that found in most mammals. Finally, the pulmonary veins enter the left atrium with four large veins.     

Determination of esophageal probe insertion length based on standing and sitting height

The present study derives simple formulas for the prediction of optimal insertion length of an esophageal temperature-sensitive probe from the measurements of either standing or sitting height. The formulas assume that the optimal site for an esophageal temperature probe is in the region of the esophagus bounded by the left ventricle and aorta, corresponding to the level of the eighth and ninth thoracic vertebrae (T8 and T9, respectively). An esophageal probe was constructed of polyethylene tubing containing 1-cm segments of alternating radiopaque and nonradiopaque tubing in the distal 20 cm of the probe. The probe was inserted through a nostril into the esophagus of 20 subjects (12 males and 8 females) of various heights (range 163-194.6 cm) and weights (range 52.2-100.8 kg), and lateral chest radiograms were obtained for determination of the insertion length of the probe (L) required to situate the probe in the retrocardiac esophagus. Analysis of the radiograms demonstrated that, at the level of the intervertebral disc between T8 and T9, the probe was below the tracheal bifurcation and close to the left ventricle. The distance from the nasal flare to this level showed a good correlation with the subject's stretched stature (r2 = 0.71) and sitting height (r2 = 0.86). The following equations were derived to predict the placement of the esophageal probe at the T8/T9 level based on standing height: L (CM) = 0.228 x (standing height) - 0.194, and sitting height: L (cm) = 0.479 x (sitting height) - 4.44.     

Biosynthesis of prostaglandins E2 and F2a by lung tissue in hypoxia and hyperthermia]

Effect of a hypoxia and hyperthermia on endogenous biosynthesis of prostaglandins E2 and F2 alpha by tissues of lungs was studied. The effect of high temperature (43 degrees C-45 degrees C during I hour) and tissue hypoxemia by, exposition in an atmosphere with carbon monoxide, stimulated rise of formation of derivative of prostaglandins in the right and left lung: PGF2 alpha in 1.2-2.6, and PG E2-in 1.48-2.7 times accordingly. The parity between prostaglandins after experiment remained same, as well as in control group. The increase of a level of biosynthesis of investigated prostaglandins had more expressed character in a right lung, than in left. The reasons, leading to such significant growth of amounts of prostaglandins can be a few. One of them--it, apparently, growth of an amount of substrates for a phospholipase A2 and cyclooxygenase, as to for want of given temperature of a body is sharply increased a state of fluidity of membranes, leading to violation stability of membrane of phospholipids and further their destruction. Second--possible increase of activity of enzymes, leading to derivation of eicosanoids-cyclooxygenase and (or) of the phospholipase A2, leading to mobilization of an arachidonic acid from phospholipids of membranes. In a tissue of lungs after the hyperthermia and hypoxemia the decrease of amount of c-AMP on a background of c-GMP amount growth in the right and in the left lung was observed. For want of than, described above legitimacy was saved, in which the amount c-AMP in a right lung prevails over left. During realization of experiment interesting legitimacy-process, leading to growth the contents PG E2 was detected, also conducted to decrease of an amount c-AMP. The reduction of an amount c-AMP is possible, apparently, to explain the cell destruction, as heating in these parameters stimulates the cell apoptosis development, which conducts to reduction of an amount c-AMP inside a cell.     

Effects of ischemia on lung macrophages

Angiogenesis after pulmonary ischemia is initiated by reactive O(2) species and is dependent on CXC chemokine growth factors, and its magnitude is correlated with the number of lavaged macrophages. After complete obstruction of the left pulmonary artery in mice, the left lung is isolated from the peripheral circulation until 5-7 days later, when a new systemic vasculature invades the lung parenchyma. Consequently, this model offers a unique opportunity to study the differentiation and/or proliferation of monocyte-derived cells within the lung. In this study, we questioned whether macrophage subpopulations were differentially expressed and which subset contributed to growth factor release. We characterized the change in number of all macrophages (MHCII(int), CD11C+), alveolar macrophages (MHCII(int), CD11C+, CD11B-) and mature lung macrophages (MHCII(int), CD11C+, CD11B+) in left lungs from mice immediately (0 h) or 24 h after left pulmonary artery ligation (LPAL). In left lung homogenates, only lung macrophages increased 24 h after LPAL (vs. 0 h; p<0.05). No changes in proliferation were seen in any subset by PCNA expression (0 h vs. 24 h lungs). When the number of monocytic cells was reduced with clodronate liposomes, systemic blood flow to the left lung 14 days after LPAL decreased by 42% (p<0.01) compared to vehicle controls. Furthermore, when alveolar macrophages and lung macrophages were sorted and studied in vitro, only lung macrophages secreted the chemokine MIP-2α (ELISA). These data suggest that ischemic stress within the lung contributes to the differentiation of immature monocytes to lung macrophages within the first 24 h after LPAL. Lung macrophages but not alveolar macrophages increase and secrete the proangiogenic chemokine MIP-2α. Overall, an increase in the number of lung macrophages appears to be critical for neovascularization in the lung, since clodronate treatment decreased their number and attenuated functional angiogenesis.     

Reflex cardiorespiratory responses to pulmonary vascular congestion

The purpose of these studies was to determine the reflex responses of the cardiovascular system and central inspiratory activity caused by pulmonary vascular congestion. We used a canine preparation in which the left lung was isolated in situ and could be exposed to a variety of stimuli, including distension of the pulmonary capillaries with blood, without direct mechanical or chemical alterations on the circulation. We found that lung expansion to 30 cmH2O and stimulation of nerve endings of the left lung with capsaicin caused pronounced transient reflex bradycardia (-30 to -50 beats/min) and hypotension (-25 to -40 mmHg) and caused reflex cessation of inspiratory activity. Pressurizing the left pulmonary vessels by injecting blood in volumes sufficient to raise pulmonary transcapillary pressures to 30 mmHg caused no changes in heart rate, systemic arterial pressure, or inspiratory muscle activity. These results lead us to conclude that pulmonary vascular congestion does not stimulate pulmonary C-fibers or any other nerve endings to such a degree as to cause detectable changes in blood pressure, heart rate, or central inspiratory activity. Morphometric analysis revealed distended capillaries engorged with blood, but the alveolar wall surface area was not increased which raises the possibility that expansion of the alveolar membrane may be needed to mechanically initiate the C-fiber reflex.     

Chemokine Localization in Bronchial Angiogenesis

Angiogenesis in the lung involves the systemic bronchial vasculature and becomes prominent when chronic inflammation prevails. Mechanisms for neovascularization following pulmonary ischemia include growth factor transit from ischemic parenchyma to upstream bronchial arteries, inflammatory cell migration/recruitment through the perfusing artery, and paracrine effects of lung cells within the left bronchus, the niche where arteriogenesis takes place. We analyzed left lung bronchoalveolar lavage (BAL) fluid and left bronchus homogenates after left pulmonary artery ligation (LPAL) in rats, immediately after the onset of ischemia (0 h), 6 h and 24 h later. Additionally, we tested the effectiveness of dexamethasone on decreasing inflammation (0–24 h LPAL) and angiogenesis at early (3 d LPAL; bronchial endothelial proliferation) and late (14 d LPAL; blood flow) stages. After LPAL (6 h), BAL protein, total inflammatory cells, macrophages, and polymorphonuclear cells increased significantly. In parallel, pro-angiogenic CXC chemokines increased in BAL and the left main-stem bronchus (CXCL1) or only within the bronchus (CXCL2). Dexamethasone treatment reduced total BAL protein, inflammatory cells (total and polymorphonuclear cells), and CXCL1 but not CXCL2 in BAL. By contrast, no decrease was seen in either chemokine within the bronchial tissue, in proliferating bronchial endothelial cells, or in systemic perfusion of the left lung. Our results confirm the presence of CXC chemokines within BAL fluid as well as within the left mainstem bronchus. Despite significant reduction in lung injury and inflammation with dexamethasone treatment, chemokine expression within the bronchial tissue as well as angiogenesis were not affected. Our results suggest that early changes within the bronchial niche contribute to subsequent neovascularization during pulmonary ischemia.