High Plasma Lipid Levels Reduce Efficacy of Adenovirus-Mediated Gene Therapy.

Adenoviruses are very efficient vectors for delivering therapeutic genes in preclinical and clinical trials. However, randomized controlled human trials have often been lacking clear clinically relevant results. We hypothesized that high lipid levels and specific lipoproteins could significantly decrease adenoviral transduction efficiency in vivo. Here we demonstrate that mice on a high fat diet have lower transgene expression compared to mice on a regular chow. In addition, on a high fat diet, ApoE-/- mice have much higher plasma transgene levels compared to LDLR-deficient mice. We also found that specific lipoprotein receptors play an important role in adenoviral transduction. These findings suggest that high plasma lipid levels, especially apoE-containing lipoproteins, reduce efficacy of adenoviral transduction in mice, which implies that high cholesterol levels in humans could be protective against viral infections and also lead to insufficient transgene expression in clinical trials using adenoviral vectors.

Recurrence of sarcoid granulomas in lung transplant recipients is common and does not affect overall survival.

BACKGROUND: Sarcoidosis represents 2,5% of all indications for lung transplantation and criteria are generally assumed to be the same as for pulmonary fibrosis. Recurrence of granulomas in transplanted lungs has earlier been proved to derive from recipient immune cells, but its role in relation to lung function and overall survival after lung transplantation remains uncertain. OBJECTIVE: To identify recurrent granuloma in transbronchial biopsies in patients receiving lung transplant because of sarcoidosis, and relate the findings to overall survival and lung function. DESIGN: A total of 620 patients were transplanted at this centre from 1992 until august 2012. This study comprised all patients (n=25) transplanted due to pulmonary sarcoidosis. Lung functions, trans-bronchial biopsies, and survival were compared in patients with and without recurrence of granulomas. Granulomas were defined as non-necrotizing epitheloid granulomas with multinucleated giant cells according to standard criteria (formation of epitheloid giant cells) without presence of infection. CONCLUSIONS: Approximately 30% of lung transplant recipients due to sarcoidosis have recurrence of sarcoid granulomas. Recurrence of granulomas does not affect overall survival or lung function.

The boson peak of amyloid fibrils: probing the softness of protein aggregates by inelastic neutron scattering.

Proteins and polypeptides are characterized by low-frequency vibrations in the terahertz regime responsible for the so-called "boson peak". The shape and position of this peak are related to the mechanical properties of peptide chains. Amyloid fibrils are ordered macromolecular assemblies, spontaneously formed in nature, characterized by unique biological and nanomechanical properties. In this work, we investigate the effects of the amyloid state and its polymorphism on the boson peak. We used inelastic neutron scattering to probe low-frequency vibrations of the glucagon polypeptide in the native state and in two different amyloid morphologies in both dry and hydrated sample states. The data show that amyloid fibril formation and hydration state affect the softness of the polypeptide not only by changing the distribution of vibrational modes but also, and most significantly, the dissipative mechanisms of collective low-frequency vibrations provided by water-protein and protein-protein interactions. We show how the morphology of the fibril is able to tune these effects. Atomic fluctuations were also measured by elastic neutron scattering. The data confirm that any effect of protein aggregation on fluctuation amplitudes is essentially due to changes in surface exposure to hydration water. The results demonstrate the importance of protein-protein and protein-water interactions in the dynamics and mechanics of amyloid fibrils.

Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation.

A 44-year-old woman underwent left single-lung transplantation for end-stage emphysema due to α1-antitrypsin deficiency in January 2010. Cyclosporine, azathioprine, and prednisolone were administered for immunosuppression and antithymocyte globulin for induction therapy at the time of transplantation. Routine examination of a lung biopsy, 4 months after transplantation, showed nonspecific, diffuse interstitial inflammation with alveolar septal fibrosis. The patient's clinical status and imaging studies, consistent with nonspecific interstitial pneumonitis, which was considered as signs of acute rejection, worsened within 2 weeks, despite high-dose steroids, change of calcineurin inhibitor, and plasmapheresis. Within a few days after a single, 10-mg, intravenous dose of alemtuzumab, the patient's health improved markedly. She has remained stable for 4 months on a standard, ambulatory, posttransplant antirejection drug regimen. We have since successfully treated with alemtuzumab three additional patients who developed interstitial lung injury after lung transplantation, who are also summarized in this report.

Mutation in APOA1 predicts increased risk of ischaemic heart disease and total mortality without low HDL cholesterol levels.

OBJECTIVES: To determine whether mutations in APOA1 affect levels of high-density lipoprotein (HDL) cholesterol and to predict risk of ischaemic heart disease (IHD) and total mortality in the general population. BACKGROUND: Epidemiologically, risk of IHD is inversely related to HDL cholesterol levels. Mutations in apolipoprotein (apo) A-I, the major protein constituent of HDL, might be associated with low HDL cholesterol and predispose to IHD and early death. DESIGN: We resequenced APOA1 in 190 individuals and examined the effect of mutations on HDL cholesterol, risk of IHD, myocardial infarction (MI) and mortality in 10 440 individuals in the prospective Copenhagen City Heart Study followed for 31 years. Results were validated in an independent case-control study (n = 16 035). Additionally, we determined plasma ratios of mutant to wildtype (WT) apoA-I in human heterozygotes and functional effects of mutations in adenovirus-transfected mice. RESULTS: We identified a new mutation, A164S (1 : 500 in the general population), which predicted hazard ratios for IHD, MI and total mortality of 3.2 [95% confidence interval (CI): 1.6-6.5], 5.5 (95% CI: 2.6-11.7) and 2.5 (95% CI: 1.3-4.8), respectively, in heterozygotes compared with noncarriers. Mean reduction in survival time in heterozygotes was 10 years (P < 0.0001). Results for IHD and MI were confirmed in the case-control study. Furthermore, the ratio of mutant S164 to WT A164 apoA-I in plasma of heterozygotes was reduced. In addition, A164S heterozygotes had normal plasma lipid and lipoprotein levels, including HDL cholesterol and apoA-I, and this finding was confirmed in adenovirus-transfected mice. CONCLUSIONS: A164S is the first mutation in APOA1 to be described that predicts an increased risk of IHD, MI and total mortality without low HDL cholesterol levels.

Complement factor H deficiency and endocapillary glomerulonephritis due to paternal isodisomy and a novel factor H mutation.

Complement factor H (CFH) is a regulator of the alternative complement activation pathway. Mutations in the CFH gene are associated with atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis type II and C3 glomerulonephritis. Here, we report a 6-month-old CFH-deficient child presenting with endocapillary glomerulonephritis rather than membranoproliferative glomerulonephritis (MPGN) or C3 glomerulonephritis. Sequence analyses showed homozygosity for a novel CFH missense mutation (Pro139Ser) associated with severely decreased CFH plasma concentration (<6%) but normal mRNA splicing and expression. The father was heterozygous carrier of the mutation, but the mother was a non-carrier. Thus, a large deletion in the maternal CFH locus or uniparental isodisomy was suspected. Polymorphic markers across chromosome 1 showed homozygosity for the paternal allele in all markers and a lack of the maternal allele in six informative markers. This combined with a comparative genomic hybridization assay demonstrated paternal isodisomy. Uniparental isodisomy increases the risk of homozygous variations in other genes on the affected chromosome. Therefore, we analyzed other susceptibility genes on chromosome 1 and found no sequence variation in membrane cofactor protein, but homozygosity for the common deletion of CFH-related proteins 1 and 3, which may contribute to the early onset of disease.

Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy.

A single report has associated mutations in TMEM43 (LUMA) with a distinctive form of arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed at performing mutational analysis of the gene and characterizing the associated immunohistochemical features. Sixty-five unrelated patients (55 fulfilling Task Force criteria and 10 borderline cases) were screened for mutations in TMEM43. Immunohistochemistry with anti-TMEM43, anti-plakoglobin, anti-plakophilin-2, anti-connexin-43, and anti-emerin antibodies was performed on myocardium from TMEM43-positive patients (n = 3) and healthy controls (n = 3). The genetic screening identified heterozygous variants in two families: one reported mutation (c.1073C> T; in two related patients) and one novel variant (c.705+ 7G> A; in one patient) of unknown significance. All three patients fulfilled Task Force criteria and did not carry mutations in any other ARVC-related gene. Immunostaining with TMEM43 antibody showed intense staining of the sarcolemma. The signal level was reduced in all the three TMEM43-positive patients. Immunostaining with plakoglobin-specific antibody also showed reduced signal levels in the three carriers. All patients displayed a similar immunoreactive signal for plakophilin-2, connexin-43, and emerin. In conclusion, two TMEM43 sequence variants were identified in this Danish ARVC cohort. Evaluation of the expression of TMEM43 showed a unique cardiac localization. The immunoreactive signal for the desmosomal protein plakoglobin was reduced in mutation carriers. The TMEM43 gene underlies a distinctive form of ARVC which may share a final common pathway with desmosome-associated ARVC.

Renal cell apoptosis in human lupus nephritis: a histological study.

Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney biopsies from 35 patients with lupus nephritis by means of terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling (TUNEL). Five samples of normal kidney tissue served as control specimens. We did not observe apoptotic glomerular cells in any of the control or nephritis biopsies. Scarce apoptotic tubular cells were seen in 13 of 35 (37%) of the nephritis specimens and in two of five (40%) of the control sections. Within the SLE cohort, patients with TUNEL-positive tubular cells in their renal biopsies had significantly higher activity index scores for tubulointerstitial mononuclear cell infiltration than patients without apoptotic tubular cells in their biopsies (P = 0.01). Furthermore, the level of tubular cell apoptosis displayed a statistically significant, positive correlation with the activity index score for mononuclear cell infiltration (r(s) = 0.472, P = 0.004) but not with scores for other activity or chronicity index components. These observations indicate that the degree of tubular cell apoptosis correlates with the severity of tubulointerstitial inflammation in SLE-associated nephritis. However, our findings do not suggest that apoptotic renal cells constitute a quantitatively important source of auto-antibody-inducing nuclear auto-antigens in human lupus nephritis.

Cardiac sarcoidosis and heart transplantation: a report of four consecutive patients.

Heart transplantation (HTx) is a well-established treatment for severe cardiac failure. However, HTx for cardiac sarcoidosis is rare; less than 80 patients have been reported worldwide. In many patients, the diagnosis was not made prior to HTx. The aim of this study was to describe the use of HTx in the treatment of severe cardiac sarcoidosis. The series was comprised of four Caucasian patients (1 male, 3 females), aged 25-57 years. HTx were performed in the period 1990-2006. None of the patients had clinically overt extra-cardiac sarcoidosis. In one patient the diagnosis of sarcoidosis was proven prior to HTx. In three patients, all with dilated cardiomyopathy due to myocardial sarcoidosis, the final diagnosis was obtained by examination of the explanted heart. Arrythmias (supraventricular and ventricular), heart block, mitral valve insufficiency and dilated cardiomyopathy were prominent clinical features. None of the patients had recurrence of sarcoid disease in the allograft. Two patients are long-term survivors and two are deceased, one of primary graft failure, the other from Cytomegalovirus myocarditis. In conclusion, HTx is a viable treatment for cardiac sarcoidosis with end stage cardiac failure. Cardiac sarcoidosis is difficult to diagnose. Myocardial biopsy has a low diagnostic sensitivity. However, when the newest non-invasive diagnostic methods, including magnetic resonance imaging and positron emission tomography, are applied, an endomyocardial biopsy should not be mandatory to make a diagnosis of cardiac sarcoidosis.

A foot and mouth disease simulation exercise involving the five Nordic countries.

Simulation exercises are considered a very valuable tool for testing contingency plans established for the control and eradication of rapid spreading animal diseases such as foot and mouth disease, classical swine fever and avian influenza. An inter-Nordic simulation exercise was conducted in 2005 with the objective of testing the national foot and mouth disease contingency plans adopted respectively by Denmark, Finland, Iceland, Norway and Sweden. The Central Veterinary Administrations of the five countries jointly prepared a scenario which involved about 40 livestock holdings, 4 reindeer flocks, 6 slaughterhouses and approximately 500 people. An Excel spreadsheet with information on the events to take place and the timetable to follow during the exercise was a valuable tool for ensuring that the exercise was kept on track. The evaluation of the exercise dealt both with inter-Nordic activities and the activities of individual countries.

Aspergillus infection in lung transplant patients: incidence and prognosis.

Lung transplant recipients experience a particularly high incidence of Aspergillus infection in comparison with other solid-organ transplantations. This study was conducted to determine the incidence of Aspergillus colonisation and invasive aspergillosis, and the impact on long-term survival associated with Aspergillus infection. A retrospective study of 362 consecutive lung transplant patients from a single national centre who were transplanted 1992-2003 were studied. Twenty-seven patients were excluded due to incomplete or missing files. A total of 105/335 (31%) patients had evidence of Aspergillus infection (colonisation or invasion), including 83 (25%) patients with colonisation and 22 (6%) patients with radiographic or histological evidence of invasive disease. Most of the infections occurred within the first 3 months after transplantation. Cystic fibrosis (CF) patients had higher incidences of colonisation and invasive disease [15 (42%) and 4 (11%) of 36 patients] than non-CF patients [68 (23%) and 18 (6%) of 299 patients] (P = 0.01). Invasive aspergillosis was associated with 58% mortality after 2 years, whereas colonisation was not associated with early increased mortality but was associated with increased mortality after 5 years compared to non-infected patients (P < 0.05). An analysis of demographic factors showed that donor age [OR 1.40 per decade (95% CI 1.10-1.80)], ischaemia time [OR 1.17 per hour increase (95% CI 1.01-1.39)], and use of daclizumab versus polyclonal induction [OR 2.05 (95% CI 1.14-3.75)] were independent risk factors for Aspergillus infection. Invasive aspergillosis was associated with early and high mortality in lung transplant patients. Colonisation with Aspergillus was also associated with a significant increase in mortality after 5 years. CF patients have a higher incidence of Aspergillus infection than non-CF patients.

Morphometric examination of native lungs in human lung allograft recipients.

The aim of the study was to estimate the degree of lung damage in patients with alpha(1)-antitrypsin (alpha1AT) deficiency, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) at the time of lung transplantation. Using unbiased stereological methods, lung-, bronchial- and vessel-volume, capillary length, and alveolar surface area and densities were estimated in recipient lungs from 21 consecutive patients with pre-transplant diagnoses including COPD (n=7), alpha1AT deficiency (n=6) and CF (n=8). Six unused adult donor lungs served as controls. Information relating to patient demography and pre-transplant lung function was obtained by retrospective chart review. Disease groups differed significantly with respect to demographics and pre-transplant lung function. Total lung volume was similar in all groups. Bronchial volume was significantly larger in CF patients compared to the control group (p<0.0001) and to the other two diagnostic groups: alpha1AT deficiency (p=0.0001) and COPD (p<0.0001). Alveolar surface density and capillary length density were significantly lower in patients with alpha1AT deficiency and COPD compared to controls (p<0.0001, respectively) and to patients with CF (p<0.0002, respectively). There were no correlations between clinical lung function and morphometric measurements. We conclude that unbiased microscopic stereological morphometry is an evolving science with the potential to elucidate pulmonary disease pathogenesis.

Adhesion of T and B lymphocytes to mouse atherosclerotic aortas: association with lesion topology and VCAM-1 expression.

OBJECTIVE: Although T and B lymphocytes accumulate in atherosclerotic lesions and play a key role in their growth, the mechanisms involved in the adhesion and recruitment of T and B lymphocytes by the lesions have not been resolved. The aim of this study was to compare T and B lymphocyte adhesion to atherosclerotic arteries and to test the role of VCAM-1 and ICAM-1. MATERIAL AND METHODS: T and B lymphocytes were labelled with red and green fluorescent dyes and incubated with freshly isolated aortas from apolipoprotein-E-deficient mice. In some experiments the aortas were pre-incubated with specific monoclonal antibodies. After washing, the adhering cells were detected by confocal laser scanning microscopy. RESULTS: The number of T and B lymphocytes that adhered to the aortic intimal surface was similar in both lesioned and non-lesioned areas and in the shoulder region of the lesions. However, the adhesion of T and B lymphocytes was significantly higher in the shoulder regions compared with the lesioned (p<0.0001) and non-lesioned areas of the aorta (p<0.0001). After pre-incubation of the aortas with antibodies against VCAM-1 or ICAM-1, the lymphocyte adhesions in lesioned areas were 42 % (p = 0.04) and 55 % (p = 0.17), respectively, of those in lesioned areas that had been pre-incubated with a control antibody. However, although VCAM-1 protein expression was most pronounced in the shoulder region, the lymphocyte adhesions in the shoulder region and in non-lesioned areas were unaffected by pre-incubation with VCAM-1 antibodies. CONCLUSIONS: The results suggest that adhesion of T and B lymphocytes to mouse aortic endothelium is similar, is affected by lesion topology and is dependent on VCAM-1 expression over the core of atherosclerotic lesions.

Recurrent sarcoid granulomas in a transplanted lung derive from recipient immune cells.

From 1992-2004, single lung transplantation has been performed in seven patients with end-stage pulmonary sarcoidosis at the Danish National Centre for Lung Transplantation. The objective was to assess whether recurrent sarcoid granulomas in the lung graft are derived from recipient or donor immune cells. Three patients had sarcoid recurrence in the lung graft, but none had clinically overt extra-thoracic sarcoidosis. Graft sex-mismatch was present in one patient, a 52-yr-old female having a lung graft from a male donor. In order to discriminate between recipient and donor cells fluorescence in situ hybridisation (FISH), using probes for both X- and Y-chromosomes, was applied on transbronchial lung biopsies (TBB) from the lung graft containing sarcoid granulomas. The recipient's explanted lung contained multiple active sarcoid granulomas. TBB from the implanted donor lung 5 months after transplantation showed sarcoid granulomas. FISH showed that the immune cells in the granulomas were X-chromosome positive and Y-chromosome negative and, therefore, were derived from the recipient. In conclusion, the results indicate that recurrent sarcoid granulomas in the transplanted lung are derived from recipient's immune cells, having colonised the lung allograft.

Macrophages overloaded with tissue debris in Wegener's granulomatosis.

OBJECTIVES: To analyse some scavenging related molecules in Wegener's granulomatosis (WG) macrophages. METHODS: Immunohistochemical staining of lung, nasopharynx, and skin for macrophage markers related to scavenging (macrophage scavenger receptor MARCO, collagenase-1 and gelatinase-B), formation of multinuclear foreign body giant cells (ADAM 9/meltrin-gamma and ADAM 12/meltrin-alpha), and cell debris derived from neutrophils, endothelial cells and mast cells (specific granule protein 28 (SGP28), von Willebrand factor (vWF) and mast cell tryptase, respectively). TechMate staining robot and biotin-streptavidin protocol were used. RESULTS: Some macrophages were activated and expressed collagenase-1 and gelatinase-B. Approximately 5% of macrophages expressed scavenger receptor, whereas 20-30% were meltrin positive. Interstitial and granuloma associated macrophages and giant cells contained partly undigested, immunoreactive SGP28-, vWF- and tryptase-positive cell rests and collagenous matrix. Lymphocytic follicles with germinal centres were found in the same areas. CONCLUSION: In WG tissue lesions macrophage and giant cells seem to be overwhelmed by the bulk to be scavenged. Despite cellular activation and continuing maturation to professional scavenger receptor (MARCO) and meltrin positive multinuclear giant cells combined with an organisation into granulomas, macrophages still contain partially undigested cell and tissue rests. This necrotic and damaged self may be the driving force for the formation of giant cell ("foreign body") granulomas. This, together with the local formation of secondary lymphatic follicles (with germinal centres), indicates active local antigen processing and presentation.

Macrophage and lymphocyte chimerism in bronchoalveolar lavage cells from human lung allograft recipients.

BACKGROUND: Chimerism is suggested to predict a more favourable prognosis in solid organ transplantation. MATERIAL AND METHOD: Forty-eight bronchoalveolar lavages from 10 patients (5 females and 5 males) who had received sex-mismatched donor lungs were monitored for varying periods of time, of up to 2 years, at regular intervals (median 3.0 (0.5-24) months). To investigate the chimerism in macrophages and lymphocytes in bronchoalveolar lavage cells a cloned 2.12 kilobase large biotinylated Y-chromosome-specific DNA-probe was used for in situ hybridization. RESULTS: Donor macrophages disappeared in seven patients within the first 6 months after surgery (median 3.0 (1-6) months). But 15% donor macrophages could be detected in one patient 1 year and 10% in 2 patients two years after surgery. Donor lymphocytes disappeared in all patients within 3 months (median 1 (0.5-3) months). There was no correlation between periods or severity of acute rejection and percentage of donor macrophages and donor lymphocytes in bronchoalveolar lavage. None of the patients developed obliterative bronchiolitis. CONCLUSION: Macrophage chimerism in lung may exist for several years. Whilst our results do not elucidate the role of local macrophage chimerism, they do not currently support the view that chimerism prevents rejection.

Bronchial arterial devascularization. An experimental study in pigs.

OBJECTIVE: The lungs have dual blood supply: The bronchial and the pulmonary circulation. The importance of bronchial circulation is disputed. The purpose of this study was to establish an experimental model to examine the importance of the bronchial artery. DESIGN: Comparative porcine experimental study. The surgical technique was evaluated in group A (n = 9). Group B (n = 8) underwent left bronchial arterial devascularization. In group C (n = 9) the left principal bronchus was devascularized, transsected, and reanastomosed. In groups B and C bronchial mucosal blood flow was studied with laser-Doppler velocimetry. Devascularization was controlled by angiography at section, and specimens were examined with conventional histology and scanning electron microscopy. The right bronchus served as control. RESULTS: In group B devascularization caused considerable, yet insignificant reduction in bronchial mucosal blood flow index (p = 0.1282) postoperatively, and after 1 week (p = 0.0678), insignificant histologic (p > 0.2) changes, and no scanning electron microscopy differences. In group C devascularization with bronchial transsection caused significant reduction in mucosal blood flow index (p = 0.0277) postoperatively and after 1 week (p = 0.0277), significant histologic changes (p = 0.0277), and insignificant (p = 0.069) changes in scanning electron microscopy. CONCLUSION: Bronchial arterial devascularization with transsection caused significant physiologic and morphologic changes, and a model with bronchial devascularization should include transsection.

Cloning and characterization of the cyclic guanosine monophosphate-inhibited phosphodiesterase PDE3A expressed in mouse oocyte.

In the preovulatory follicle, oocyte meiotic resumption occurs soon after the LH surge and is associated with a decrease in cAMP. Inhibition of cAMP degradation blocks germinal vesicle breakdown as well as activation of meiotic promoting factor, both hallmarks of reentry into the cell cycle. In situ and pharmacological analysis of rodent ovaries suggested the presence of a phosphodiesterase 3 (PDE3) in the germ cell but not the somatic cell compartment. Here we have investigated the structure and properties of the PDE form expressed in mouse oocytes. Polymerase chain reactions using a mouse oocyte cDNA library as a template, and primers based on the conserved sequence of rat and human PDE3As, yielded partial fragments corresponding to mouse PDE3A. Further screening of the mouse oocyte cDNA library and subsequent ligation of individual cDNA clones yielded PDE3A cDNA containing the entire coding region of mouse PDE3A. To determine the kinetic properties of this PDE, the cDNAs encoding the full-length PDE3A and NH(2)-truncation forms Delta 1 (Delta346aa) and Delta 2 (Delta608aa) were expressed in mouse Leydig tumor cells. Whereas the full-length recombinant protein was always found in the particulate fraction, the Delta 1 and Delta 2 truncated PDE3As were recovered mostly in the soluble fraction. The Michaelis constant values for hydrolysis of cAMP of PDE3A Delta 1 and PDE3A Delta 2 were similar to those of intact full-length PDE3A or oocyte PDE (0.2-0.5 microM). More importantly, there was good correlation between the rank of potency of selective and nonselective compounds in inhibiting recombinant PDE3A or PDE activity derived from cumulus-oocyte complexes and in blocking resumption of meiosis. These data provide evidence that the PDE expressed in the oocyte is a soluble form of PDE3A and that activity of this enzyme is involved in the control of resumption of meiosis.

Bronchial transsection and reanastomosis in pigs with and without bronchial arterial circulation.

BACKGROUND: The bronchial artery may be vital to the bronchi and lung parenchyma, but results of lung transplantation have raised doubts. This study was performed to examine the effect of bronchial arterial devascularization on bronchial morphology after bronchial transsection and reanastomosis. METHODS: In 6 pigs (study group), the left main bronchus was transsected, reanastomosed, and devascularized. Six control pigs had the same operation without devascularization. After 1 week, bronchial arterial angiography was performed, and specimens were examined with conventional histology and scanning electron microscopy. RESULTS: Histology showed significant changes (inflammation, edema, and fibrosis) in bronchi and lung parenchyma of the study group compared with the unoperated side (p = 0.028) and with the control group (p = 0.050). Scanning electron microscopy showed significant ciliary denudation in the study group's left bronchus compared with the unoperated side (p = 0.043) and with the control group (p = 0.0071). CONCLUSIONS: The loss of cilia of the bronchial epithelium and the occurrence of inflammation, edema, and fibrosis in bronchi and lung parenchyma 1 week postoperatively were significantly related to the absence of the bronchial arterial circulation.