Large Pulmonary Vessels Research Articles

МАСС-СПЕКТРОМЕТРИЧЕСКАЯ БАЗА ДАННЫХ ДЛЯ ИДЕНТИФИКАЦИИ ДИРОФИЛЯРИЙ

The results of using MS MALDI-TOF for diagnosing helminths are modest, but recent studies show the promise of this method for reliable identification of nematodes. The article provides information on compiling a database of dirofilaria (Dirofilaria immitis, Dirofilaria repens). The protein spectra obtained from 58 D. repens and 118 D. immitis specimens were analyzed using a software mass spectrometer Bruker Daltonics Germany. Adult D. repens specimens and their fragments were obtained from 52 patients of medical organizations in the Rostov region and the South of Russia and from 6 dogs from veterinary clinics in the Rostov region. Adult D. immitis were removed from the heart and large pulmonary vessels of 11 animals of the canine family. The obtained numerical values determine the number of reference spectra and, on their basis, create databases for the identification of the nematode of the genus Dirofilaria. Type and version of the database management system: Bruker Daltonics Biotyper. Database size 562 KB (0,562 MB): D. repens – 145 KB, D. immitis – 417 KB. Based on the data obtained a certificate of registration.

Fibroblast growth factor 10 reverses cigarette smoke- and elastase-induced emphysema and pulmonary hypertension in mice.

COPD is an incurable disease and a leading cause of death worldwide. In mice, fibroblast growth factor (FGF)10 is essential for lung morphogenesis, and in humans, polymorphisms in the human FGF10 gene correlate with an increased susceptibility to develop COPD. We analysed FGF10 signalling in human lung sections and isolated cells from healthy donor, smoker and COPD lungs. The development of emphysema and PH was investigated in Fgf10+/- and Fgfr2b+/- (FGF receptor 2b) mice upon chronic exposure to cigarette smoke. In addition, we overexpressed FGF10 in mice following elastase- or cigarette smoke-induced emphysema and pulmonary hypertension (PH). We found impaired FGF10 expression in human lung alveolar walls and in primary interstitial COPD lung fibroblasts. In contrast, FGF10 expression was increased in large pulmonary vessels in COPD lungs. Consequently, we identified impaired FGF10 signalling in alveolar walls as an integral part of the pathomechanism that leads to emphysema and PH development: mice with impaired FGF10 signalling (Fgf10+/- and Fgfr2b+/- ) spontaneously developed lung emphysema, PH and other typical pathomechanistic features that generally arise in response to cigarette smoke exposure. In a therapeutic approach, FGF10 overexpression successfully restored lung alveolar and vascular structure in mice with established cigarette smoke- and elastase-induced emphysema and PH. FGF10 treatment triggered an initial increase in the number of alveolar type 2 cells that gradually returned to the basal level when the FGF10-mediated repair process progressed. Therefore, the application of recombinant FGF10 or stimulation of the downstream signalling cascade might represent a novel therapeutic strategy in the future.

Venous injection of a triphasic calcium-based implant in a sheep model of pulmonary embolism demonstrates minimal acute systemic effects

PurposeImplant leakage is the most common complication of vertebral augmentation. Alternative injectable materials must demonstrate intravascular safety comparable to or better than polymethyl methacrylate (PMMA). This study assessed the systemic effects of a triphasic calcium-based implant or PMMA injected directly into the femoral vein in a large animal model designed to mimic severe intravascular implant leakage.MethodsSix skeletally mature female sheep were randomly assigned (n = 3) to either the PMMA or the triphasic implant (AGN1, composition: calcium sulfate, β-tricalcium phosphate, brushite) treatment group. Femoral veins of each sheep were directly injected with 0.5 mL of implant material to mimic leakage volumes reported during PMMA vertebroplasty. To compare acute systemic effects of the materials, cardiovascular parameters, laboratory coagulation markers, and calcium and sulfate serum levels were monitored for 60 min after implant injection. Thrombotic and embolic events were evaluated by radiologic imaging, necropsy, and histopathology.ResultsHeart rate, systemic arterial blood pressure, arterial oxygenation, arterial carbon dioxide content, and coagulation markers remained within physiological range after either AGN1 or PMMA injection. No blood flow interruption in the larger pulmonary vessels was observed in either group. Lung histopathology revealed that the severity of thrombotic changes after AGN1 injection was minimal to slight, while changes after PMMA injection were minimal to massive.ConclusionAcute systemic effects of intravascular AGN1 appeared to be comparable to or less than that of intravascular PMMA. Furthermore, in this preliminary study, the severity and incidence of pulmonary histological changes were lower for AGN1 compared to PMMA.

Cardiopulmonary Injury in the Syrian Hamster Model of COVID-19.

The Syrian hamster has proved useful in the evaluation of therapeutics and vaccines for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). To advance the model for preclinical studies, we conducted serial sacrifice of lungs, large pulmonary vessels, and hearts from male and female Syrian hamsters for days 1–4, and 8 post-infection (dpi) following infection with a high dose of SARS-CoV-2. Evaluation of microscopic lung histopathology scores suggests 4 and 8 dpi as prime indicators in the evaluation of moderate pathology with bronchial hyperplasia, alveolar involvement and bronchiolization being key assessments of lung disease and recovery, respectively. In addition, neutrophil levels, red blood cell count and hematocrit showed significant increases during early infection. We present histological evidence of severe damage to the pulmonary vasculature with extensive leukocyte transmigration and the loss of endothelial cells and tunica media. Our evidence of endothelial and inflammatory cell death in the pulmonary vessels suggests endothelialitis secondary to SARS-CoV-2 epithelial cell infection as a possible determinant of the pathological findings along with the host inflammatory response. Lastly, pathological examination of the heart revealed evidence for intracardiac platelet/fibrin aggregates in male and female hamsters on 8 dpi, which might be indicative of a hypercoagulative state in these animals.

Sonographic assessment of pediatric chest wall thickness and width of the intercostal space: correlation with anthropometric data and implications for needle decompression

BackgroundEmergent needle decompression in children is a rare event for emergency medicine and critical care providers. Hereby, risk of injury of intrathoracic structures is high and knowledge of age-specific values of chest wall thickness and width of the intercostal space (ICS) is crucial to avoid injuries. Investigation of the correlation of chest wall thickness and width of the intercostal space with age and body dimension like weight and height could provide guidance on depth of insertion and choice of the needle.MethodsWe performed a prospective observational clinical trial in a pediatric surgery operating room that included a convenient sample of children aged 0–10 years undergoing elective surgery. Chest wall thickness and width of the intercostal space were measured with ultrasound at 2nd ICS midclavicular line (MCL) and 4th ICS anterior axillary line (AAL). Correlation of these measures with age, height, weight, BMI and Broselow color was calculated. Furthermore, intra-class correlation coefficient was calculated as a measure of reproducibility and the presence of vital structures (e.g., heart, thymus gland, large pulmonary vessels) at the possible insertion sites for needle decompression was investigated.ResultsOf 410 potentially eligible patients, 300 were included in the study. Correlation of chest wall thickness was moderate with weight (2nd ICS MCL: r = 0.57; 4th ICS MCL: r = 0.64) and BMI (r = 0.44 and r = 0.6) and was lower with age (r = 0.38 for both intercostal spaces), height (r = 0.42 and r = 0.40) and Broselow color (r = 0.42 and r = 0.38). Correlation of width of the ICS with anthropometric data was generally stronger, with height showing the strongest, albeit not really strong, correlation (r = 0.71 and r = 0.62). Intra-class correlation was excellent with an ICC of 0.93. Vital structures were significantly more often present at 2nd ICS MCL then at 4th ICS AAL (14 vs. 2 patients; p = 0.0042).ConclusionsCorrelation of chest wall thickness and width of the intercostal space with anthropometric data is at most moderate. Insertion depth and width of the intercostal space can therefore not be predicted accurately from anthropometric data. Ultrasound assessment of the thoracic wall appears to be a reliable technique and could therefore assist in reducing the risk of injury and increasing decompression success.Trial registration German clinical trials register, DRKS00014973, Registered February 11th 2019, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00014973

The vasa vasorum of the large pulmonary vessels are involved in COVID-19.

DEAR EDITOR In our manuscript “COVID-19: a closer look at the pathology in two autopsied cases. Is the pericyte at the center of the pathological process in COVID-19?” ;1 published in Volume 11, 2021 issue of Autopsy Case Reports; Figures 3B, 4A, 4B, and 4D show thrombosis within the walls of large pulmonary vessels. These locations of thrombosis may represent the location of the vasa vasorum of these pulmonary vessels. Figures 3B and 4A may represent thrombus within vasorum externa, whilst figures 4B and 4D represent thrombus within vasorum interna.2 The significance of these sites means that both, the alveolar microcirculation and the vasa vasorum of the large pulmonary vessels are involved in the thrombotic processes in COVID-19. The latter thrombotic site would further implicate COVID-19 as a disease of the microcirculation. Boyle and Haverich3 postulated that “the involvement of the large vessels during coronavirus disease 19 (COVID-19) in both children and adults is likely due to dysfunction of their vasa vasorum and SARS-COV-2 induced microthrombosis of vasa vasorum would lead to hypoxic conditions in the adventitia.” As the world is grappling with the SARS-COV-2 pandemic, it is essential to understand the pathogenesis of COVID-19 to formulate therapeutic options. It may be that the lung is a secondary partner in COVID-19 and the pathogenesis of this disease begins in the nasopharynx,4 where there is an abundance of ACE-2 receptor sites. SARS-COV-2 interaction at the port of entry in the nasopharynx produces chemokines/cytokines,3,5 which circulates in the systemic circulation, causing endotheliopathy and subsequent thrombotic microangiopathy6 being the ultimate result.

MR properties of 19F C3F8 gas in the lungs of healthy volunteers: and apparent diffusion coefficient at 1.5T and at 3T

To measure the transverse relaxation time ( ) and apparent diffusion coefficient (ADC) of 19 F-C3 F8 gas in vivo in human lungs at 1.5T and 3T, and to determine the representative distribution of values of these parameters in a cohort of healthy volunteers. Mapping of ADC at lung inflation levels of functional residual capacity (FRC) and total lung capacity (TLC) was performed with inhaled 19 F-C3 F8 (eight subjects) and 129 Xe (six subjects) at 1.5T. mapping with 19 F-C3 F8 was performed at 1.5T (at FRC and TLC) for 8 subjects and at 3T (at TLC for seven subjects). At both FRC and TLC, the 19 F-C3 F8 ADC was smaller than the free diffusion coefficient demonstrating airway microstructural diffusion restriction. From FRC to TLC, the mean ADC significantly increased from 1.56 mm2 /s to 1.83 mm2 /s (P = .0017) for 19 F-C3 F8, and from 2.49 mm2 /s to 3.38 mm2 /s (P = .0015) for 129 Xe. The posterior-to-anterior gradient in ADC for FRC versus TLC in the superior half of the lungs was measured as 0.0308 mm2 /s per cm versus 0.0168 mm2 /s per cm for 19 F-C3 F8 and 0.0871 mm2 /s per cm versus 0.0326 mm2 /s per cm for 129 Xe. A consistent distribution of 19 F-C3 F8 values was observed in the lungs, with low values observed near the diaphragm and large pulmonary vessels. The mean across volunteers was 4.48 ms at FRC and 5.33 ms at TLC for 1.5T, and 3.78 ms at TLC for 3T. In this feasibility study, values of physiologically relevant parameters of lung microstructure measurable by MRI ( , and ADC) were established for C3 F8 in vivo lung imaging in healthy volunteers.

Valvular endocarditis associated with Helcococcus ovis in a cow in Southern Brazil

ABSTRACT: A 4-year-old cow with a history of breathing difficulty, progressive weight loss, and muffled heart sound was treated for a period of two weeks, but died and underwent necropsy examination. Macroscopic examination revealed heart with vegetative proliferative lesion firmly adhered to pulmonary valve, lungs with marked consolidation, and the presence of thrombus in vessels. There were grade II ulcers in abomasal mucosa associated to blood clots. Microscopic examination revealed marked thickening of the pulmonary valve due to the proliferation of fibrous connective tissue, inflammatory neutrophil infiltration, fibrin deposition, and a significant number of coccoid basophilic bacteria. Septic thromboemboli were present in the large and small pulmonary blood vessels suggestive of embolic pneumonia. The bacterial culture of the valve showed growth of small, nonhemolytic colonies that demonstrated satellitism to coagulase-negative staphylococci contaminating colonies, which were subjected to 16S gene sequencing and were compatible with Helcococcus ovis in GenBank. This was the first report of H. ovis endocarditis in cattle in South America.

Angiogenesis in the lung.

Both systemic (tracheal and bronchial) and pulmonary circulations perfuse the lung. However, documentation of angiogenesis of either is complicated by the presence of the other. Well-documented angiogenesis of the systemic circulations have been identified in asthma, cystic fibrosis, chronic thromboembolism and primary carcinomas. Angiogenesis of the vasa vasorum, which are branches of bronchial arteries, is seen in the walls of large pulmonary vessels after a period of chronic hypoxia. Documentation of increased pulmonary capillaries has been shown in models of chronic hypoxia, after pneumonectomy and in some carcinomas. Although endothelial cell proliferation may occur as part of the repair process in several pulmonary diseases, it is separate from the unique establishment of new functional perfusing networks defined as angiogenesis. Identification of the mechanisms driving the expansion of new vascular beds in the adult needs further investigation. Yet the growth factors and molecular mechanisms of lung angiogenesis remain difficult to separate from underlying disease sequelae.

Comparative View of Lung Vascular Endothelium of Cattle, Horses, and Water Buffalo.

Endothelium plays an important role in maintaining the vascular barrier and physiological homeostasis. Endothelium also is fundamental to the initiation and regulation of inflammation. Endothelium demonstrates phenotypic and functional heterogeneity not only among various organs but also within an organ. One of the striking examples would be the pulmonary endothelium that participates in creating blood-air barrier. Endothelium in large pulmonary blood vessels is distinct in structure and function from that lining of the pulmonary capillaries. This chapter focuses on the comparative aspects of pulmonary endothelium and highlight unique differences such as the presence of pulmonary intravascular macrophages among select species.

Non-contrast quantitative pulmonary perfusion using flow alternating inversion recovery at 3 T: A preliminary study

PurposeTo demonstrate the initial feasibility of non-contrast quantitative pulmonary perfusion imaging at 3T using flow alternating inversion recovery (FAIR), and to evaluate the intra-session and inter-session reliability of FAIR measurements at 3T. Materials and methodsNine healthy volunteers were imaged using our own implementation of FAIR pulse sequence at 3T. Quantitative FAIR perfusion, both with and without larger pulmonary vessels, was correlated with global phase contrast (PC) measured blood flow in the right pulmonary artery (RPA). The same volunteers were also imaged with SPECT perfusion using technetium-99m-macroaggregated albumin and relative dispersion (RD) was assessed between FAIR and SPECT perfusion. Four additional healthy volunteers were evaluated for FAIR repeatability, using intra-class correlation coefficient (ICC) and Bland-Altman analysis. p<0.05 was considered statistically significant. ResultsFAIR perfusion across all subjects was 858±605mL/100g/min (with vessels) and 629±294mL/100g/min (without vessels) and correlated significantly with the PC measured blood flow in the RPA (r=0.62, p<0.01 with vessels; r=0.73, p<0.001 without vessels). The median RD of FAIR perfusion across all subjects was 0.73 (with vessels) and 0.49 (without vessels), compared against 0.23 with SPECT perfusion. The intra/inter-session ICC of FAIR perfusion with vessels was 0.95/0.59 and improved to 0.96/0.72, when vessels were removed. ConclusionsNon-contrast quantitative pulmonary perfusion imaging using FAIR is feasible at 3T. This may serve as a reliable method to assess regional lung perfusion at 3T to characterize and monitor treatment response in chronic lung disease without the concerns of repeated exposure to ionizing radiation or the accumulation of exogenous contrast agent.

Loss of Kaiso expression in breast cancer cells prevents intra-vascular invasion in the lung and secondary metastasis.

The metastatic activity of breast carcinomas results from complex genetic changes in epithelial tumor cells and accounts for 90% of deaths in affected patients. Although the invasion of the local lymphatic vessels and veins by malignant breast tumor cells and their subsequent metastasis to the lung, has been recognized, the mechanisms behind the metastatic activity of breast tumor cells to other distal organs and the pathogenesis of metastatic cancer are not well understood. In this study, we utilized derivatives of the well-established and highly metastatic triple negative breast cancer (TNBC) cell line MDA-MB-231 (MDA-231) to study breast tumor metastasis in a mouse model. These MDA-231 derivatives had depleted expression of Kaiso, a POZ-ZF transcription factor that is highly expressed in malignant, triple negative breast cancers. We previously reported that Kaiso depletion attenuates the metastasis of xenografted MDA-231 cells. Herein, we describe the pathological features of the metastatic activity of parental (Kaisopositive) versus Kaisodepleted MDA-231 cells. Both Kaisopositive and Kaisodepleted MDA-231 cells metastasized from the original tumor in the mammary fat pad to the lung. However, while Kaisopositive cells formed large masses in the lung parenchyma, invaded large pulmonary blood vessels and formed secondary metastases and large tumors in the distal organs, Kaisodepleted cells metastasized only to the lung where they formed small metastatic lesions. Importantly, intravascular invasion and secondary metastases in distal organs were not observed in mice xenografted with Kaisodepleted cells. It thus appears that the lung may constitute a barrier for less invasive breast tumors such as the Kaisodepleted TNBC cells; this barrier may limit tumor growth and prevents Kaisodepleted TNBC cells from invading the pulmonary blood vessels and forming secondary metastases in distal organs.

Arteriopathy of Large Pulmonary Vessels Associated with Pulmonary Artery Hypertension

Arteriopathy of Large Pulmonary Vessels Associated with Pulmonary Artery Hypertension

Pulmonary vasculitis.

Pulmonary vasculitis encompasses inflammation in the pulmonary vasculature with involved vessels varying in caliber from large elastic arteries to capillaries. Small pulmonary capillaries are the vessels most commonly involved in vasculitis affecting the lung. The antineutrophil cytoplasmic antibody-associated vasculitides, which include granulomatosis with polyangiitis (formerly Wegener granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), are the small vessel vasculitides in which pulmonary vasculitis is most frequently observed and are the major focus of this review. Vasculitic involvement of the large pulmonary vessels as may occur in Behçet syndrome and Takayasu arteritis is also discussed.

Characterization of early neovascular response to acute lung ischemia using simultaneous 19F/1H MR molecular imaging

Angiogenesis is an important constituent of many inflammatory pulmonary diseases, which has been unappreciated until recently. Early neovascular expansion in the lungs in preclinical models and patients is very difficult to assess noninvasively, particularly quantitatively. The present study demonstrated that (19)F/(1)H MR molecular imaging with αvβ3-targeted perfluorocarbon nanoparticles can be used to directly measure neovascularity in a rat left pulmonary artery ligation (LPAL) model, which was employed to create pulmonary ischemia and induce angiogenesis. In rats 3days after LPAL, simultaneous (19)F/(1)H MR imaging at 3T revealed a marked (19)F signal in animals 2h following αvβ3-targeted perfluorocarbon nanoparticles [(19)F signal (normalized to background)=0.80±0.2] that was greater (p=0.007) than the non-targeted (0.30±0.04) and the sham-operated (0.07±0.09) control groups. Almost no (19)F signal was found in control right lung with any treatment. Competitive blockade of the integrin-targeted particles greatly decreased the (19)F signal (p=0.002) and was equivalent to the non-targeted control group. Fluorescent and light microscopy illustrated heavy decorating of vessel walls in and around large bronchi and large pulmonary vessels. Focal segmental regions of neovessel expansion were also noted in the lung periphery. Our results demonstrate that (19)F/(1)H MR molecular imaging with αvβ3-targeted perfluorocarbon nanoparticles provides a means to assess the extent of systemic neovascularization in the lung.

In vivo quantification of pulmonary inflammation in relation to emphysema severity via partial volume corrected (18)F-FDG-PET using computer-assisted analysis of diagnostic chest CT.

Our aim was to quantify the degree of pulmonary inflammation associated with centrilobular emphysema using fluoro-18-2-fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET) and diagnostic unenhanced computed tomography (CT) based image segmentation and partial volume correction. Forty-nine subjects, with variable amounts of centrilobular emphysema, who had prior diagnostic unenhanced chest CT and either (18)F-FDG-PET or (18)F-FDG-PET/CT were selected. Lung parenchymal volume (L) (in cm³) excluding large and small pulmonary vessels, emphysema volume (E) (in cm³) based on a -910HU threshold, fraction of lung emphysema (F=E/L), and mean attenuation (HU) of non-emphysematous lung parenchyma (A) were calculated from CT images using the image analysis software 3DVIEWNIX. Lung uncorrected maximum SUV (USUVmax) was measured manually from PET images on a dedicated workstation. A first level of partial volume correction (PVC) of lung SUVmax to account for presence and degree of macroscopic emphysematous air space was calculated as CSUVmax=USUVmax/(1-F). A second level of PVC of non-emphysematous lung SUVmax to account for the mixture of air and lung parenchyma at the microscopic level was then estimated as CCSUVmax=CSUVmax/(A+1000/1040), assuming that air is -1000HU in attenuation and gasless lung parenchyma is 40HU in attenuation. The correlation of F with USUVmax, CSUVmax, CCSUVmax, % change between CSUVmax and USUVmax (%UC), and % change between CCSUVmax and USUVmax (%UCC) were then tested. The results showed that USUVmax was not significantly correlated with F (r=-.0973, P=0.34). CSUVmax (r=0.4660, P<0.0001) and CCSUVmax were significantly positively correlated with F (r=0.5479, P<0.0001), as were %UC (r=0.9383, P<0.0001) and %UCC (r=0.9369, P<0.0001). In conclusion, the degree of pulmonary inflammation increases with emphysema severity based on (18)F-FDG-PET or (18)F-FDG-PET/CT assessment, but is only detectable when (18)F-FDG uptake is corrected for the partial volume effect based on data provided from diagnostic chest CT images. These results support the notion that pulmonary inflammation plays an important role in the pathophysiology of emphysema. This novel image analysis approach has great potential for practical, accurate, and precise combined structural-functional PET quantification of pulmonary inflammation in patients with emphysema or other pulmonary conditions, although further validation and refinement will be required.

Tumors of the Pulmonary Artery and Veins

The pulmonary vasculature may be involved by different primary and secondary tumors. Poorly differentiated and undifferentiated sarcomas are the most common primary tumors of the pulmonary arteries. They tend to affect the large caliber pulmonary vessels and present with predominantly intraluminal growth. Pulmonary and mediastinal metastasis are common, and prognosis is poor. Clinical and imaging manifestations may mimic those of pulmonary embolism. Dyspnea, chest pain, cough, and hemoptysis are the most common presenting symptoms. Primary sarcomas arising from the central pulmonary veins are less common than their arterial counterpart. Secondary involvement of the pulmonary arteries and veins by primary and metastatic pulmonary malignancies is more common. Tumoral embolism may also affect the pulmonary arteries. They may develop from different intrathoracic and extrathoracic malignancies and may be indistinguishable from venous thromboembolism. It may manifest as cor pulmonale with right cardiac strain and dilated pulmonary arteries. Computed tomography, magnetic resonance imaging, and fluorodeoxyglucose positron emission tomography may help in the differentiation between these 2 conditions.

Video-assisted thoracic surgery pneumonectomy: the first case report in Poland.

Minimally invasive video-assisted thoracic surgery (VATS) lobectomy has proved to be equal and in some aspects superior to open lobectomy in T1 and T2 lung cancers. Indications for VATS pneumonectomy however are still not clearly defined and strictly limited. The minimally invasive VATS pneumonectomy can be undertaken in patients with centrally located tumors without extended invasion of the large pulmonary vessels, chest wall, pericardium, mediastinal structures or proximal part of the main bronchus and when sleeve resection is not feasible (T2). We present a case of a patient who underwent left VATS pneumonectomy due to left lung cancer. Based on the preoperative examinations any kind of less extensive resection than pneumonectomy was excluded. Our VATS technique consisted of three incisions: two ports and a 5-6 cm long utility incision without any kind of rib spreading. The whole of the procedure was controlled on the monitor via a thoracoscope and the technique of resection was described in detail. Total surgery time was 130 min and blood loss was 150 ml. The chest tube was removed on the 2nd post-operative day and the patient was discharged home on the 8th postoperative day. The final histopathological examination confirmed squamous cell lung cancer (T2aN0M0 stage IB). In the authors’ opinion VATS pneumonectomy should be performed only in centers with extensive experience in minimally invasive VATS lobectomy. Despite limited indications for VATS pneumonectomy, if the patients fulfill the VATS pneumonectomy inclusion criteria they may gain from all the advantages of minimally invasive techniques.

Transgenic expression of human matrix metalloproteinase-1 attenuates pulmonary arterial hypertension in mice

PAH (pulmonary arterial hypertension) is a debilitating and life-threatening disease, often affecting young people. We specifically expressed human MMP-1 (matrix metalloproteinase-1) in mouse macrophages and examined its effects in attenuating the decompensating features of MCT (monocrotaline)-induced PAH. Measurement of RV (right ventricular) pressure revealed a 2.5-fold increase after treatment with MCT, which was reduced to 1.5-fold in MMP-1 transgenic mice. There was conspicuous pulmonary inflammation with chronic infiltration of mononuclear cells after the administration of MCT, which was significantly diminished in transgenic mice. Furthermore, transgenic mice showed decreased collagen deposition compared with WT (wild-type). Staining for Mac-3 (macrophage-3) and α-SMA (α-smooth muscle actin) revealed extensive infiltration of macrophages and medial hypertrophy of large pulmonary vessels with complete occlusion of small arteries respectively. These changes were markedly reduced in MMP-1 transgenic mice compared with WT. Western blotting for molecules involved in cell multiplication and proliferation depicted a significant decrease in the lung tissue of transgenic mice after the treatment with MCT. In conclusion, the present study demonstrated that transgenic expression of human MMP-1 decreased proliferation of smooth muscle cells and prevented excessive deposition of collagen in the pulmonary arterial tree. Our results indicate that up-regulation of MMP-1 could attenuate the debilitation of human PAH and provide an option for therapeutic intervention.

Contribution of serial and parallel microperfusion to spatial variability in pulmonary inter- and intra-acinar blood flow.

This study presents a theoretical model of combined series and parallel perfusion in the human pulmonary acinus that maintains computational simplicity while capturing some important features of acinar structure. The model provides a transition between existing models of perfusion in the large pulmonary blood vessels and the pulmonary microcirculation. Arterioles and venules are represented as distinct elastic vessels that follow the branching structure of the acinar airways. These vessels are assumed to be joined at each generation by capillary sheets that cover the alveoli present at that generation, forming a "ladderlike" structure. Compared with a model structure in which capillary beds connect only the most distal blood vessels in the acinus, the model with combined serial and parallel perfusion provides greater capacity for increased blood flow in the lung via capillary recruitment when the blood pressure is elevated. Stratification of acinar perfusion emerges in the model, with red blood cell transit time significantly larger in the distal portion of the acinus compared with the proximal portion. This proximal-to-distal pattern of perfusion may act in concert with diffusional screening to optimize the potential for gas exchange.