Bronchial Perfusion Research Articles

Exosomal secreted SCIMP regulates communication between macrophages and neutrophils in pneumonia

In pneumonia, the deficient or delayed pathogen clearance can lead to pathogen proliferation and subsequent overactive immune responses, inducing acute lung injury (ALI). While screening human genome coding genes using our peripheral blood cell chemotactic platform, we unexpectedly find SLP adaptor and CSK interacting membrane protein (SCIMP), a protein with neutrophil chemotactic activity secreted during ALI. However, the specific role of SCIMP in ALI remains unclear. In this study, we investigate the secretion of SCIMP in exosomes (SCIMPexo) by macrophages after bacterial stimulation, both in vitro and in vivo. We observe a significant increase in the levels of SCIMPexo in bronchoalveolar lavage fluid and serum of pneumonia patients. We also find that bronchial perfusion with SCIMPexo or SCIMP N-terminal peptides increases the survival rate of the ALI model. This occurs due to the chemoattraction and activation of peripheral neutrophils dependent on formyl peptide receptor 1/2 (FPR1/2). Conversely, exosome suppressors and FPR1/2 antagonists decrease the survival rate in the lethal ALI model. Scimp-deficient and Fpr1/2-deficient mice also have lower survival rates and shorter survival times than wild-type mice. However, bronchial perfusion of SCIMP rescues Scimp-deficient mice but not Fpr1/2-deficient mice. Collectively, our findings suggest that the macrophage-SCIMP-FPRs-neutrophil axis plays a vital role in the innate immune process underlying ALI.

Effect of Sex Differences in Silicotic Mice.

Mechanisms of silicosis, caused by the inhalation of silica are still unclear, and the effect of sex on silicosis has rarely been reported. The purpose of this study was to investigate whether sex affects the silicotic lesions and the progressive fibrotic responses in silicosis. Our study showed that sex had no significant effect on the area of silicon nodules and the collagen deposition after a one-time bronchial perfusion of silica. Immunohistochemical staining showed that CD68 and the transforming growth factor-β1 (TGF-β1) were positive in male and female silicotic mice. In addition, the western blot results showed that the fibrosis-related factors type I collagen (COL I), α-smooth muscle actin (α-SMA), vimentin, TGF-β1, p-SMAD2/3, inflammatory-related factors interleukin 6 (IL 6), interleukin 1β (IL 1β), and senescence-related factors p16 and p21 were up-regulated in silicotic mice and there was no difference between female or male mice exposed to silica. The expression of TGF-β1, p-SMAD2/3, p16, and p21 were downregulated in the early stage of female silicotic mice, compared to the males. Thus, despite differences in the expression of certain factors, there was no overall difference in the progressive fibrosis between female and male mice in silicosis. These results thus provide a new perspective for studying the pathological development of silicosis.

Regulatory effect of Ac-SDKP on phosphorylated heat shock protein 27/SNAI1 pathway in silicotic rats

Objective: To study the effect of anti-fibrotic tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on phosphorylated heat shock protein 27 (P-HSP27) and zinc finger family transcriptional repressor 1 (SNAI1) expression to explore the anti-silicosis fibrosis effect of Ac-SDKP. Methods: In December 2014, the rat silicosis animal model was prepared by one-time bronchial infusion of silicon dioxide (SiO(2)) dust. 80 SPF healthy adult Wistar rats were selected, and the rats were divided into 8 groups according to the random number table method, 10 in each group. Model control group for 4 weeks (feeding for 4 weeks) , model control group for 8 weeks (feeding for 8 weeks) : bronchial perfusion with normal saline 1.0 ml per animal. Silicosis model group for 4 weeks (feeding for 4 weeks) and silicosis model group for 8 weeks (feeding for 8 weeks) : bronchial perfusion of 50 mg/ml SiO(2) suspension 1.0 ml per animal. Ac-SDKP administration group for 4 weeks (feeding for 4 weeks) , Ac-SDKP administration group for 8 weeks (feeding for 8 weeks) : Ac-SDKP 800 μg·kg(-1)·d(-1) was administered by intraperitoneal pump. Ac-SDKP preventive treatment group: 48 h after Ac-SDKP 800 μg·kg(-1)·d(-1) administration, bronchial perfusion of SiO(2) suspension 1.0 ml per animal, raised for 8 weeks. Ac-SDKP anti-fibrosis treatment group: after bronchial perfusion of 1.0 ml of SiO(2) suspension for 4 weeks, Ac-SDKP 800 μg·kg(-1)·d(-1) was administered for 4 weeks. Western blotting was used to detect the expression of P-HSP27, SNAI1, α-smooth muscle actin (α-SMA) , and collage typeⅠ and Ⅲ in each group. The expression of P-HSP27 and SNAI1 was detected by immunohistochemistry, and the co-localized expression of P-HSP27 and α-SMA was detected by laser confocal microscopy. Results: Compared with the model control group, the expressions of P-HSP27, SNAI1, α-SMA, and collage typeⅠ and Ⅲ in the silicosis fibrosis area of the rats in the silicosis model group were enhanced, and the differences were statistically significant (P<0.05) . After Ac-SDKP intervention, compared with silicosis model group for 8 weeks, the expressions of P-HSP27, SNAI1 α-SMA, and collage typeⅠ and Ⅲ in the Ac-SDKP preventive and anti-fibrosis treatment groups were significantly decreased, and the differences were statistically significant (P<0.05) . However, the expressions of P-HSP27 SNAI1, and collage typeⅠ and Ⅲ between the Ac-SDKP administration group and the model control group did not change significantly, and the differences were not statistically significant (P>0.05) . Laser confocal results showed that the positive cells expressing P-HSP27 and α-SMA in the lung tissue of the silicosis model group were more than those in the model control group. Compared with the silicosis model group, the Ac-SDKP prevention and anti-fibrosis treatment groups expressing the positive cells of P-HSP27 and α-SMA decreased. Compared with the model control group for 8 weeks, there were some double-positive cells expressing P-HSP27 and α-SMA in the nodules of the silicosis model group for 8 weeks. Conclusion: Ac-SDKP may play an anti-silicic fibrosis effect by regulating the P-HSP27/SNAI1 pathway.

Mechanisms of DNA Abnormal Methylation in the Development of Lung Cancer in Rats

In order to study the mechanism of abnormal deoxyribonucleic acid methylation in the process of lung cancer in rats, Wistar rats are used as the research object. The lung cancer model of rats is established by bronchial perfusion of carcinogens. Hematoxylin-eosin staining is used to observe the pathological changes of lung tissue in rats. The overall methylation level of genome is analyzed by immunohistochemistry, and the methylation status is detected by methylation specific polymerase chain reaction. The results show that the nuclei of normal bronchial epithelial cells are brown and yellow uder optical microscope. With the development of carcinogenesis, the staining gradually fades to light yellow in the infiltrating nuclei of cancer cells. Compared with normal bronchial epithelial cells, the optical density and integrated optical density values of 5-mC immunohistochemistry decrease. The methylation frequency of p16 gene in atypical hyperplasia, carcinoma in situ and invasive cancer tissues is significantly higher than that in normal and proliferative tissues. The methylation frequency of p57 gene is significantly higher in carcinoma in situ and invasive tissues than in normal and proliferative tissues. Abnormal methylation-mediated down-regulation of p16 and p57 gene transcription may be an important molecular biological event in carcinogenesis of lung cancer rats induced by carcinogens. There are still some shortcomings in the research process, but the results of the study still provide some reference and guidance for exploring more precise mechanism in the future. Therefore, this study is a significant research topic.

Criteria for enhancing mucus transport: a systematic scoping review

Background: Uncertainty exists regarding the physiological basis of physiotherapy strategies to facilitate mucus clearance. The aim of this review was to describe the physiological factors and intrinsic conditions that facilitate airway mucus transport. Method: A scoping review was performed. A systematic literature search of six databases was executed. Eligibility criteria were applied by two researchers to reach the aim of the review. Papers were identified independently by two reviewers on title, abstract and full-text level. Any discrepancies were discussed with a third reviewer. Results: The search identified 35 papers published between 1975 and 2015. These differed significantly in terms of outcome measures, measurement techniques and methodologies and included animal studies, laboratory investigations, and the use of small human samples. Nine key factors influencing mucus transport were identified. These include: temperature and humidity, bronchial perfusion, ATP, forced expiratory technique and cough, generation of oscillation, ventilation patterns/airflow, epithelial differences, mucus properties and positioning. Conclusion: This review provides a framework for factors/conditions influencing mucus transport. Existing physiotherapy strategies for augmentation of airway mucus clearance can now be evaluated against the framework and new modalities informed.

Application of fixing lung by bronchial perfusion in practice

中国原发性肺癌诊疗规范（2015年版）提出肺叶或全肺切除标本可从支气管灌注固定液，使得肺组织充分固定，但在实际工作中，通过支气管灌注固定肺组织，产生的积极作用以及操作注意事项一直少有文献报道，作者结合本科室的多年的实际操作经验，对通过支气管灌注固定肺组织的方法，以及该方法对于临床实践和后续检测工作的影响，提出见解，以期提高病理技术，帮助病理和临床医务人员更好地诊断。

Value of dual-input perfusion of 320 row CT on the efficacy evaluation of small cell lung cancer

Objective To discuss the value of dual-input perfusion of 320 row CT on the efficacy evaluation of small cell lung cancer (SCLC). Methods A total of 18 patients with SCLC confirmed by pathology who received cisplatin plus etoposide chemotherapy between June 2016 and June 2018 in the 8th Medical Center of Chinese PLA General Hospital were collected. All patients received 320 row CT perfusion scan at 3 time points before chemotherapy, after 2 cycles and 4 cycles of chemotherapy. Tumor size, perfusion pseudo color map and bronchial arterial blood flow (BF), pulmonary flow (PF) and perfusion index (PI) were obtained. The efficacy and adverse reactions were evaluated. The single factor analysis was used to make the group comparison. Pearson test was used to make correlation analysis. Results Two patients after 2 cycles of chemotherapy had complete remission (CR), another 2 patients after 4 cycles of chemotherapy had CR, and 3 patients of the above 4 cases with CR had abundant BF; after 4 cycles of chemotherapy, 7 cases had partial remission (PR), 6 cases had stable disease (SD), 1 patient had progression of disease (PD). Dual-input perfusion of 320 row CT showed that 10 cases had the tumor area 15 cm2 before the treatment. There was a negative correlation between PI and the tumor area (r=-0.694, P = 0.026) on patients with the tumor area 15 cm2 (P > 0.05). One case had Ⅳ degree of bone marrow suppression, and obvious adverse reactions were not seen in the rest of the patients. Conclusion Dual-input perfusion of 320 row CT based on the simple imaging can make an accurate quantitative judgement of the effect of SCLC according to perfusion parameter, which provides a new basis for curative effect evaluation on SCLC. Key words: Small cell lung carcinoma; Pulmonary perfusion imaging; Dual-input perfusion CT; Treatment outcome

Assessment of bronchial and pulmonary blood supply in non-small cell lung cancer subtypes using computed tomography perfusion.

The aim of this study was to investigate the dual blood supply of non-small cell lung cancer (NSCLC) and its association with tumor subtype, size, and stage, using computed tomography perfusion (CTP). A total of 54 patients (median age, 65 years; range, 42-79 years; 15 women, 39 men) with suspected lung cancer underwent a CTP scan of the lung tumor. Pulmonary and bronchial vasculature regions of interest were used to calculate independently CTP parameters (blood flow [BF], blood volume [BV], and mean transit time [MTT]) of the tumor tissue. The mean and maximum pulmonary and bronchial perfusion indexes (PImean and PImax) were calculated. The tumoral volume and the largest tumoral diameter were assessed. Differences in CTP parameters and indexes among NSCLC subtypes, tumor stages and tumor dimensions were analyzed using non-parametric tests. According to biopsy, 37 patients had NSCLC (22 adenocarcinomas [ACs], 8 squamous cell carcinomas [SCCs], 7 large-cell carcinomas [LCC]). The mean bronchial BF/pulmonary BF, bronchial BV/pulmonary BV, and bronchial MTT/pulmonary MTT was 41.2 ± 30.0/36.9 ± 24.2 mL/100 mL/min, 11.4 ± 9.7/10.4 ± 9.4 mL/100 mL, and 11.4 ± 4.3/14.9 ± 4.4 seconds, respectively. In general, higher bronchial BF than pulmonary BF was observed in NSCLC (P = 0.014). Using a tumoral volume cutoff of 3.5 cm, a significant difference in pulmonary PImax was found (P = 0.028). There was a significantly higher mean pulmonary BF in LCCs and SCCs compared with ACs (P = 0.018 and P = 0.044, respectively), whereas the mean bronchial BF was only significantly higher in LCCs compared with ACs (P = 0.024). Correspondingly, the PImax was significantly higher in LCCs and SCCs than in ACs (P = 0.001 for both). Differences between bronchial and pulmonary PImean and PImax among T stages and Union Internationale Contre le Cancer stages were not statistically significant (P values ranging from 0.691 to 0.753). The known dual blood supply of NSCLC, which depends on tumor size and histological subtype, is reflected in CTP parameters, with parameters depending both on tumor size and histological subtype. This has to be accounted for when analyzing NSCLC with CTP.

Protective effect of resveratrol against acute lung injury induced by lipopolysaccharide via inhibiting the myd88-dependent Toll-like receptor 4 signaling pathway.

Resveratrol, a polyphenol mainly present in grapes and red wine, demonstrated varied pharmacological activities. The protective effects of resveratrol on acute lung injury(ALI) induced by lipopolysaccharide(LPS) have remained elusive. The present study investigated whether the protective effect of resveratrol on ALI induced by LPS was via inhibiting the myeloid differentiation primary response gene(myd88)‑dependent toll‑like receptor(TLR)4 signaling pathway. Mice were pretreated with 5 or 45mg/kg resveratrol for threedays prior to bronchial perfusion with 25mg/kg LPS. At 12h after surgery, the ratio of the wet to the dry (w/d) lung was calculated to assess tissue edema. Histological changes of the lungs were detected using hematoxylin and eosin staining and the protein expression levels of TLR4, myd88 and nuclear factor kappa‑light‑chain‑enhancer of activatedB cells (NF‑κB) were measured by western blot analysis. The concentration of interleukin (IL)‑6 and cyclooxygenase (COX)‑2 in the bronchoalveolar lavage fluid were detected by ELISA. The results showed that resveratrol can suppress the edema, inflammatory cell infiltration and alveolar structure damage of lungs in mice with ALI and decrease the lung w/d ratio. Additionally, resveratrol markedly decreased the expression of TLR4, myd88 and NF‑κB and decreased the concentration of inflammatory cytokines, including IL‑6 and COX‑2. Therefore, it can be concluded that resveratrol has a protective effect against ALI induced by LPS, at least in part by inhibiting the myd88‑dependent TLR4 signaling pathway. In conclusion, resveratrol pretreatment has a protective effect against LPS‑induced ALI in mice, which indicates that resveratrol may serve as a potential therapeutic agent for treating ALI in the clinic.

A New Lung Preservation Technique through Bronchial Artery Perfusion on Ex-Vivo Lung

Purpose Airway hypoxia due to microvascular loss may be a predisposing factor for subsequent fibrotic remodeling in allografts, resulting in suboptimal transplant outcomes in lung transplantation. Ex-vivo lung perfusion (EVLP) is a novel strategy for lung allograft preservation that keeps the organs at physiological protective conditions. Modifying EVLP strategy, we have developed a new lung preservation technique focusing on airway protection through bronchial artery perfusion. Methods and Materials Using heart-lung blocks harvested from Lewis rats, we have developed a model where bronchial circulation (using another cannula from descending aorta, retrogradely) was synchronously perfused in addition to pulmonary circulation with acellular Steen solution on EVLP (the scheme of the model is shown in Fig 1 ). Rat lungs after 1 hour cold preservation, perfused and ventilated on EVLP for 4 hours were evaluated and lungs with bronchial artery perfusion were compared with those without bronchial perfusion on EVLP. The studies were performed based on our rat EVLP protocol that has proven to be reliable with at least 4 hours of duration with stable results. Results At 4 hours on EVLP, bronchial artery perfusion was associated with significantly better preserved oxygenation and better compliance in lung allografts through reduced glucose consumption and increased ATP level as compared to the control group. Conclusions Bronchial artery perfusion on EVLP may be a new lung preservation strategy that breaks through the current major limitation in hypoxic transplant airways after lung transplantation.

The Effects of N-acetyl-seryl-aspartyl-lysyl-proline on Expression of NF-κb and MCP-1 in Rats with Silicosis

In the present study, we developed silicosis of rat model by bronchial perfusion SiO2 dust, and intervenes with AcSDKP, immunohisto chemistry was used to detect NF-κb and MCP-1 expression in lung tissue, and positive cells were counted. We found that compared with silicotic model group, the positive cells of NF-κb and MCP-1 were decreased significantly in anti-fibrosis treatment of AcSDKP group. The findings suggest that AcSDKP could inhibit the expression of NF-κb and MCP-1 in lung tissue of silicosos, this may be related to AcSDKP inhibit of macrophage infiltration in lung tissue and reduced the degree of dust alveolitis.

The murine bronchopulmonary microcirculation in hapten-induced inflammation

The clinical observation of central bronchial artery hypertrophy in chronic lung inflammation suggests the possibility that the bronchial circulation may also participate in adaptive responses in peripheral lung inflammation. To investigate the potential role of the bronchial microcirculation in peripheral lung inflammation, we developed a murine model of lung inflammation using the intratracheal instillation of the peptide-hapten trinitrophenol in presensitized mice. Clinical parameters indicated a peak inflammatory response at 96 hours. Similarly, gross and microscopic evidence of inflammation was observed 96 hours after antigen instillation. Using a forced oscillation technique to probe peripheral lung mechanics at 96 hours, we detected no change in central airway resistance (P > .05), but a significant increase in peripheral tissue resistance (P < .05). The structure of the bronchial circulation was investigated by microsphere occlusion of the pulmonary circulation and corrosion casting of the bronchial circulation. SEM of the bronchial artery casts demonstrated (1) the presence of the peripheral bronchial circulation in mice, (2) interconnections of the two systems in the distal bronchial arteries and at the level of alveolar capillaries, and (3) functional evidence of increased bronchial perfusion of alveolar capillaries during mononuclear inflammation. These results suggest an important adaptive role of the bronchial circulation in pulmonary inflammation.

Blood flow distribution within the airway wall.

Altered perfusion of the bronchial mucosal plexus relative to the adventitial plexus may contribute to geometric changes in the airway wall and lumen. We studied bronchial perfusion distribution in sheep by using fluorescent microspheres at baseline and during intrabronchial artery challenge with methacholine chloride (MCh; n = 7). Additionally, we measured airway resistance (Raw) during MCh with control or increased perfusion (n = 9). Raw with MCh was significantly greater for high than control flow. Microspheres in histological sections lodged predominantly in the mucosa (60%), and this was not altered by MCh. However, more microspheres lodged in airways >1-mm in diameter during MCh and increased perfusion than MCh and control flow. In airways < or =1 mm in diameter, fewer microspheres lodged during control than increased flow. If the number of microspheres represents regional agonist access to airway smooth muscle, then the differences observed in Raw can be explained by the distribution of agonist. During challenge, there was greater MCh delivery to larger airways during increased flow and less delivery to smaller airways during control flow. The results demonstrate the effects of axial perfusion distribution on Raw.

Pulmonary and bronchial circulations: contributions to heat and water exchange in isolated lungs.

The relative contribution of the pulmonary and bronchial circulatory systems to heat and water exchange in normal lungs was evaluated in 20 isolated, in situ perfused dog lungs and in four patients undergoing elective cardiopulmonary bypass. In isolated dog lungs, if the pulmonary artery was perfused at a nominal flow rate (0.5 l/min), bronchial artery perfusion (up to 70 ml/min) did not significantly affect the expired gas temperature. When the lungs were not perfused through either system, 8 min of ventilation with cool, dry gas decreased the temperature of the expired gas by 6.2 +/- 1.4 degrees C. Selective perfusion of bronchial arteries at 68 +/- 10 mmHg resulted in a mean flow rate of 28 +/- 16 ml/min and increased the average temperature of the expired gas by 0.6 degrees C. An increase in the rate of bronchial arterial perfusion to 55 +/- 14 ml/min increased the average temperature of the expired gas by 1.3 degrees C. The time constant for equilibration of tritiated water between the perfusate and the lung parenchyma was 130 +/- 33 min for pulmonary arterial perfusion and 35 +/- 13 min for combined bronchial and pulmonary perfusion, which indicated that filtration of water from high-pressure bronchial vessels facilitated water exchange in the lung interstitium. The rate of tracer equilibration was similar between the perfusate and gas in both variants of perfusion, but the ratios of tracer gas to perfusate were different (0.42 +/- 0.06 for pulmonary, 0.98 +/- 0.07 for combined), which indicates that bronchial vessels contribute mainly to the hydration of the bronchial mucosa. In humans, the bronchial blood flow was capable of maintaining heat supply after the initiation of cardiopulmonary bypass. Before bypass, when both pulmonary and bronchial blood flow were present, the mean time constant of the temperature decay after a switch to ventilation with cool, dry gas was 35 +/- 12 s. The average temperature difference between the blood and expired gas was 2.4 +/- 0.50 degrees C. After 5 min of dry gas ventilation, the temperature difference between the expired gas and initial blood temperature decreased an average of 3.8 +/- 0.06 degrees C (P < 0.05). The time constant of temperature decay increased to 56 +/- 14 s (P < 0.05). We conclude that bronchial perfusion has a less important role in the temperature balance of the respiratory tract compared with pulmonary arterial perfusion because heat flux is "flow limited" but is important in providing water for hydration of the mucosal surface and interstitial compartments of peribronchial tissues.

The role of the bronchial vasculature in soluble particle clearance.

Although a role for the airway circulation in the clearance of inhaled particles is generally assumed, there is little information to confirm its importance. We studied the effects of decreased bronchial blood flow on the uptake of the soluble tracer technetium=99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) from subcarinal airways in sheep (n = 7). The bronchial artery was cannulated and perfused with autologous blood at a control flow (0.6 mL/min/kg) or when the perfusion pump was stopped (no flow). (99m)Tc-DTPA (6-10 microL) was delivered by a microspray nozzle inserted through a bronchoscope to a fourth-generation bronchus both during control blood flow conditions and no-flow conditions. Airway retention (by scintigraphy) and blood uptake were monitored for 30 min after the local deposition of (99m(Tc-DTPA. During control flow conditions, 30 min after the delivery of the radiolabel, 21% of the tracer remained at the deposition site. Of the total delivered tracer, maximum blood uptake was 18% (n) = 3). When bronchial perfusion was stopped, airway retention 30 min after deposition increased to 43%, and maximum blood uptake decreased to 7% of the total delivered tracer. Although mucociliary clearance was not directly measured, radiolabel tracer was observed to move progressively from the deposition site up to larger airways and contributed to the overall removal of tracer from the site of deposition during both flow conditions. However, these results demonstrate that decreased bronchial perfusion increases airway retention by limiting vascular uptake of the soluble tracer. These results emphasize the importance of normal perfusion of the airway vasculature for uptake of therapeutic agents delivered specifically to the conducting airways.

Responsiveness of canine bronchial vasculature to excitatory stimuli and to cooling.

Changes in bronchial vascular tone, in part due to cooling during ventilation, may contribute to altered control of airflow during airway inflammation, asthma, and exercise-induced bronchoconstriction. We investigated the responses of canine bronchial vasculature to excitatory stimuli and cooling. Electrical stimulation evoked contractions in only some (8 of 88) tissues; these were phentolamine sensitive and augmented by N(omega)-nitro-L-arginine. However, sustained contractions were evoked in all tissues by phenylephrine [concentration evoking a half-maximal response (EC(50)) approximately 2 microM] or the thromboxane A(2) mimetic U-46619 (EC(50) approximately 5 nM) and less so by beta,gamma-methylene-ATP or histamine. Cooling to room temperature markedly suppressed ( approximately 75%) adrenergic responses but had no significant effect against U-46619 responses. Adrenergic responses, but not those to U-46619, were accompanied by an increase in intracellular Ca(2+) concentration. Chelerythrine (protein kinase C antagonist) markedly antagonized adrenergic responses (mean maxima reduced 39% in artery and 86% in vein) but had no significant effect against U-46619, whereas genistein (a nonspecific tyrosine kinase inhibitor) essentially abolished responses to both agonists. We conclude that cooling of the airway wall dramatically interferes with adrenergic control of bronchial perfusion but has little effect on thromboxane-mediated vasoconstriction.

気管支粘膜血流に対する術前放射線化学療法の影響

発性肺癌手術症例87例を, A群: 手術単独の75例, B群: 術前放射線化学療法 (45Gy) 後の4例, C群: 放射線化学療法 (60Gy) 後2ヵ月～5年経過後の手術症例8例の3群に分け, 術前放射線化学療法が気管支粘膜血流および気管支断端治癒に及ぼす影響を検討した.気管支粘膜血流はレーザードップラー血流計を用い, 術前, 術中, 術後 (8～10病日) に測定した.C群では周術期を通じ血流は著しく傷害されており, 気管支断端の治癒も不良であった.8例中1例には気管支断端痩を認めた.しかしA群およびB群では血流は十分に保たれ, 気管支断端の治癒も良好であった.以上より, 術前の放射線化学療法は, 慢性期には気管支粘膜血流を傷害し気管支断端治癒不良の因子となりうる.しかし現在行われている術前放射線化学療法の設定ではこれらに及ぼす影響は少ないことが示唆された.

Bronchial vascular contribution to lung lymph flow

The lymphatic vessels of the lung provide an important route for clearance of interstitial edema fluid filtered from pulmonary blood vessels. However, the importance of lung lymphatics for the removal of airway liquid filtered from the systemic circulation of the lung has not been demonstrated. We studied the contribution of the bronchial vasculature to lung lymph flow in anesthetized, ventilated sheep (n = 35). With the bronchial artery cannulated and perfused (control flow = 0.6 ml. min-1. kg-1), lymph flow from the efferent duct of the caudal mediastinal lymph node was measured 1) during increased bronchial vascular perfusion (300% of control flow); 2) with a hydrated interstitium induced by a 1-h period of left atrial hypertension and subsequent recovery, both with and without bronchial perfusion; and 3) during infusion (directly into the bronchial artery) of bradykinin, an inflammatory mediator known to cause changes in bronchial vascular permeability. Increased bronchial perfusion for 90 min resulted in an average 35% increase in lung lymph flow. During left atrial hypertension, the increase in lung lymph flow was significantly greater with bronchial perfusion (339% increase over baseline) than without bronchial perfusion (138% increase). Furthermore, recovery after left atrial hypertension was more complete after 90 min without bronchial perfusion (91%) than with bronchial perfusion (63%). Infusion of bradykinin into the bronchial artery resulted in a prompt and prolonged 107% increase in lung lymph flow. This was not seen if the same dose was infused into the pulmonary artery. Thus bronchial vascular transudate contributes significantly to lymph flow from the efferent duct of the caudal mediastinal lymph node. These results demonstrate that lymph vessels clear excess fluid from the airway wall and should be considered when evaluating the effect of vascular leak in airway obstruction.

Importance of airway blood flow on particle clearance from the lung.

The role of the airway circulation in supporting mucociliary function has been essentially unstudied. We evaluated the airway clearance of inert, insoluble particles in anesthetized ventilated sheep (n = 8), in which bronchial perfusion was controlled, to determine whether airway mucosal blood flow is essential for maintaining surface transport of particles through airways. The bronchial branch of the bronchoesophageal artery was cannulated and perfused with autologous blood at control flow (0.6 ml.min-1.kg-1) or perfusion was stopped. With the sheep in a supine position and after a steady-state 133Xe ventilation scan for designation of lung zones of interest, an inert 99mTc-labeled sulfur colloid aerosol (2.1-microns diameter) was deposited in the lung. The clearance kinetics of the radiolabeled particles were determined from the activity-time data obtained for right and left lung zones. At 60 min postdeposition of aerosol, average airway particle retention for control bronchial blood flow conditions was 57 +/- 7 (SE)% for the right and 53 +/- 8% for the left lung zones. Clearance of particles was significantly impaired when bronchial blood flow was stopped, e.g., right and left lung zones averaged 77 +/- 6 and 76 +/- 7% at 60 min, respectively (P < 0.05). These data demonstrate a significant influence of the bronchial circulation on mucociliary transport of insoluble particles. Potential mechanisms that may account for these results include the importance of the bronchial circulation for nutrient flow, maintenance of airway wall temperature and humidity, and release of mediators and sequelae associated with tissue ischemia.

Effect of methylprednisolone and prostacyclin on bronchial perfusion in lung transplantation

In an experimental investigation using modified unilateral lung transplantation in pigs, the effects of systemic administration of methylprednisolone and prostacyclin on bronchial mucosal blood flow were assessed. Laser Doppler velocimetry (LDV) and radioisotope studies using radiolabeled erythrocytes (RI) were employed to measure blood flow at the donor main carina and upper lobe carina after 3 hours of reperfusion. The recipient carina was used as a reference point. Five groups of 6 animals each were studied. Group I served as control. In group II, methylprednisolone (20 mg/kg) was administered to the recipient. In group III, prostacyclin (4 ng · kg −1 · min −1) was given to the recipient, and in group IV, prostacyclin (100 μg intravenously) was administered to the donor. In group V, prostacyclin was given to the recipient and the donor animals as in groups III and IV, respectively. In group I, bronchial blood flow at the donor main carina was 37.6% ± 2.2% (LDV) and 44.1% ± 14.8% (RI) of reference blood flow. No significant differences were found between the controls and groups II, III, and IV. In group V, bronchial blood flow was markedly increased both at the donor main carina (LDV, 39.8% ± 6.2%, p = 0.12; RI, 55.7% ± 11.4%, p < 0.2) and the donor upper lobe carina (LDV, 65.8% + 5.4%, p < 0.05; RI, 76.8% ± 21.3%, p < 0.2). We conclude that systemic administration of prostacyclin to the donor and recipient results in marked improvement of bronchial blood flow and may reduce the incidence of bronchial complications after lung transplantation.