Influence of different routes of flush perfusion on the distribution of lung preservation solutions in parenchyma and airways

Objective: The present study was performed to investigate the influence of different routes of perfusion on the distribution of the preservation solutions in the lung parenchyma and upper airways. Methods: Pigs were divided into four groups: control (n = 6), pulmonary artery (PA) (n = 6), simultaneous PA + bronchial artery (BA) (n = 8), and retrograde delivery (n = 6). After preparation and cannulation, cardioplegia solution and Euro- Collins solution (ECS) for lung preservation were given simultaneously. After removal of the heart, the double lung bloc was harvested. Following parameters were assessed: total and regional perfusion (dye-labeled microspheres), tissue water content, PA, aorta, left atrial and left ventricular pressures, cardiac output and lung temperature. Results: Our data show that flow of the ECS in lung parenchyma did not reach control values (9.4 �� 1.0 ml/min per g lung wet weight) regardless of the route of delivery (PA 6.3 �� 1.5, PA + BA 4.8 �� 0.9, retrograde 2.7 �� 0.9 ml/min per g lung wet weight). However, flow in the proximal and distal trachea were significantly increased by PA + BA delivery (0.970 �� 0.4, respectively, 0.380 �� 0.2 ml/min per g) in comparison with PA (0.023 �� 0.007, respectively, 0.024 �� 0.070 ml/min per g), retrograde (0.009 �� 0.003, respectively, 0.021 �� 0.006 ml/min per g) and control experiments (0.125 �� 0.0018, respectively, 0.105 �� 0.012 ml/g per min). Similarly the highest flow rates in the right main bronchus were achieved by PA + BA delivery (1.04 �� 0.4 ml/min per g) in comparison with 0.11 �� 0.03 in control, 0.033 �� 0.008 in PA, and 0.019 �� 0.005 ml/min per g in retrograde group. Flows in the left main bronchus were 0.09 �� 0.02 ml/min per g in control, 0.045 �� 0.012 ml/min per g in PA, and 0.027 �� 0.006 ml/min per g in retrograde group. The flow rates were significantly (P = 0.001) increased by PA + BA delivery of the storage solution (0.97 �� 0.3 ml/min per g). Conclusions: Our data show that the distribution of ECS for lung preservation is significantly improved in airway tissues (trachea and bronchi) if a simultaneous PA + BA delivery is used.

Anatomic study of the feline bronchial and vascular structures with a 64 detector-row computed tomography

Multidetector row computed tomography over the last decade is commonly used in veterinary medicine. This new technology has an increased spatial and temporal resolution, could evaluate wider scanning range in shorter scanning time, providing an advanced imaging modality. Computed tomography angiographic studies are commonly used in veterinary medicine in order to evaluate vascular structures of the abdomen and the thorax. Pulmonary pathology in feline patients is a very common condition and usually is further evaluating with computed tomography. Up to date few references of the normal computed tomographic aspects of the feline thorax are reported. In this study a computed tomographic pulmonary angiography (CTPA) protocol is reported in normal cats and is compared with the up to date anatomical references. A CTPA protocol using a 64 MDCT in our study achieved high resolution images of the pulmonary arteries, pulmonary veins and bronchial lumen till the level of minor segmental branches. Feline pulmonary bronchial parenchyma demonstrates an architecture of mixed type with a monopedial model observed in the most anatomical parts and the dichotomic aspect is seen at the accessory lobe. The arterial and venous architecture is similar to the bronchial. Statistical analysis demonstrates the linear correlation of tracheal diameter to the felines weight. Vascular variations were noticed. The pulmonary venous system enters into the left atrium through three ostia (left cranial ostia: consisted of the anastomosis of the cranial and caudal portion of the left cranial pulmonary vein; right ostia: consisted of the anastomosis of the right cranial and middle pulmonary vein; and the caudal ostia: consisted of the anastomosis of the right and left caudal pulmonary vein). In conclusion CTPA is applicable in feline patients and provides an excellent imaging of the pulmonary arterial, venous and bronchial system till the level of minor segmental branches.

Bronchial circulation after experimental lung transplantation: the effect of direct revascularization of a bronchial artery

Direct revascularization of a bronchial artery has been proposed as a measure to alleviate the problem of bronchial ischemia after lung transplantation. To assess the effect of restoration of arterial blood flow to the transplanted bronchus, bronchial mucosal blood flow was measured in a model of modified unilateral lung transplantation in pigs. Laser Doppler velocimetry (LDV) and radioisotope studies using radio-labeled erythrocytes (RI) were used to measure blood flow at the donor main carina (DC) and upper lobe carina (DUC) after 3 h of reperfusion. The recipient carina was used as a reference point; values obtained by LDV and RI were expressed as percentage of blood flow at the recipient carina. Two groups of animals were studied. In group 1 (n = 6) standard unilateral transplantation was performed; in group 2 (n = 6) a left bronchial artery was reimplanted into the descending thoracic aorta of the recipient. No differences were observed between the two groups with respect to preoperative or postoperative gas exchange or hemodynamics. In group 1, bronchial blood flow at the DC was 37.6 +/- 2.2% (LDV) and 44.1 +/- 14.8% (RI) of reference blood flow. At the DUC, blood flow was 54.9 +/- 7.7% (LDV) and 61.6 +/- 25.7% (RI) of normal flow. In group 2, blood flow was increased at the DC as measured by LDV (55.3 +/- 17.1%; p less than 0.05) and by RI (60.8 +/- 25.3%; p less than 0.2). A similar increase was found at the DUC (LDV: 81.8 +/- 19.3%; p less than 0.05; RI: 88.6 +/- 31.0%; p less than 0.2). It is concluded that there is a significant gradient of blood flow from intra- to extrapulmonary airways after lung transplantation. Reimplantation of a bronchial artery results in significant improvement of graft bronchial blood flow. Restoration of bronchial perfusion to normal levels, however, cannot be achieved, suggesting a possible defect in the microcirculation of the donor airways.

Aorto-bronchial and aorto-pulmonary fistulation after thoracic endovascular aortic repair: an analysis from the European Registry of Endovascular Aortic Repair Complications.

OBJECTIVES: To learn upon incidence, underlying mechanisms and effectiveness of treatment strategies in patients with central airway and pulmonary parenchymal aorto-bronchial fistulation after thoracic endovascular aortic repair (TEVAR). METHODS: Analysis of an international multicentre registry (European Registry of Endovascular Aortic Repair Complications) between 2001 and 2012 with a total caseload of 4680 TEVAR procedures (14 centres). RESULTS: Twenty-six patients with a median age of 70 years (interquartile range: 60-77) (35% female) were identified. The incidence of either central airway (aorto-bronchial) or pulmonary parenchymal (aorto-pulmonary) fistulation (ABPF) in the entire cohort after TEVAR in the study period was 0.56% (central airway 58%, peripheral parenchymal 42%). Atherosclerotic aneurysm formation was the leading indication for TEVAR in 15 patients (58%). The incidence of primary endoleaks after initial TEVAR was n = 10 (38%), of these 80% were either type I or type III endoleaks. Fourteen patients (54%) developed central left bronchial tree lesions, 11 patients (42%) pulmonary parenchymal lesions and 1 patient (4%) developed a tracheal lesion. The recognized mechanism of ABPF was external compression of the bronchial tree in 13 patients (50%), the majority being due to endoleak formation, further ischaemia due to extensive coverage of bronchial feeding arteries in 3 patients (12%). Inflammation and graft erosion accounted for 4 patients (30%) each. Cumulative survival during the entire study period was 39%. Among deaths, 71% were attributed to ABPF. There was no difference in survival in patients having either central airway or pulmonary parenchymal ABPF (33 vs 45%, log-rank P = 0.55). Survival with a radical surgical approach was significantly better when compared with any other treatment strategy in terms of overall survival (63 vs 32% and 63 vs 21% at 1 and 2 years, respectively), as well as in terms of fistula-related survival (63 vs 43% and 63 vs 43% at 1 and 2 years, respectively). CONCLUSIONS: ABPF is a rare but highly lethal complication after TEVAR. The leading mechanism behind ABPF seems to be a continuing external compression of either the bronchial tree or left upper lobe parenchyma. In this setting, persisting or newly developing endoleak formation seems to play a crucial role. Prognosis does not differ in patients with central airway or pulmonary parenchymal fistulation. Radical bronchial or pulmonary parenchymal repair in combination with stent graft removal and aortic reconstruction seems to be the most durable treatment strategy.

Effets de la perfusion pulsatile durant une circulation extra-corporelle

INTRODUCTION : L���utilisation de la circulation extracorporelle durant la chirurgie cardiaque est associ��e �� des probl��mes pulmonaires chez certains patients. L���utilisation d���une pression pulsatile induite par un ballon intra-aortique (BIA) pourrait diminuer la dysfonction endoth��liale et la survenue de tels ��v��nements. MAT��RIEL ET M��THODE : 12 porcs Landrace-Yorkshire ont subi une circulation extracorporelle et ont ��t�� divis��s en deux groupes et 4 porcs ont servi de contr��les sans CEC. Le premier groupe (n=6) a b��n��fici�� d���un flot pulsatile cr���� par un BIA en mode interne �� 80 battements par minute durant les 90 minutes de l���op��ration alors que le second groupe (n=6) a subi une CEC standard. Apr��s 60 minutes de reperfusion suivant la CEC, les valeurs h��modynamiques ont ��t�� ��valu��es dont les pressions art��rielles, les pressions pulmonaires, l���index cardiaque et la concentration de glucose et de lactate. Les art��res pulmonaires sont ensuite mont��es en chambre d���organe pour ��valuer la fonction endoth��liale. R��SULTATS : Les porcs avec pression pulsatile ont tendance �� produire moins de lactate sanguin apr��s 60 minutes de reperfusion. Les autres valeurs h��modynamiques sont semblables. Finalement, la relaxation �� la bradykinine est significativement meilleure dans le groupe pression pulsatile alors que la relaxation �� l���ac��tylcholine n���est pas significativement diff��rente. CONCLUSION : Ces r��sultats d��montrent que la perfusion pulsatile produite par un BIA prot��ge l���endoth��lium pulmonaire lors d'une CEC. Cet effet pourrait ��tre d�� �� une augmentation du flot bronchique qui diminuerait l���isch��mie pulmonaire ou �� une diminution de la lib��ration de cytokines et de bradykinine qui r��duirait les dommages de reperfusion.

Pulmonary neutrophil recruitment and bronchial reactivity in formaldehyde-exposed rats are modulated by mast cells and differentially by neuropeptides and nitric oxide

We have used a pharmacological approach to study the mechanisms underlying the rat lung injury and the airway reactivity changes induced by inhalation of formaldehyde (FA) (1% formalin solution, 90 min once a day, 4 days). The reactivity of isolated tracheae and intrapulmonary bronchi were assessed in dose-response curves to methacholine (MCh). Local and systemic inflammatory phenomena were evaluated in terms of leukocyte countings in bronchoalveolar lavage (BAL) fluid, blood, bone marrow lavage and spleen. Whereas the tracheal reactivity to MCh did not change, a significant bronchial hyporesponsiveness (BHR) was found after FA inhalation as compared with naive rats. Also, FA exposure significantly increased the total cell numbers in BAL, in peripheral blood and in the spleen, but did not modify the counts in bone marrow. Capsaicin hindered the increase of leukocyte number recovered in BAL fluid after FA exposure. Both compound 48/80 and indomethacin were able to prevent the lung neutrophil influx after FA, but indomethacin had no effect on that of mononuclear cells. Following FA inhalation, the treatment with sodium cromoglycate (SCG), but not with the nitric oxide (NO) synthase inhibitor L-NAME, significantly reduced the total cell number in BAL. Compound 48/80, L-NAME and SCG significantly prevented BHR to MCh after FA inhalation, whereas capsaicin was inactive in this regard. on the other hand, indomethacin exacerbated BHR. These data suggest that after FA inhalation, the resulting lung leukocyte influx and BHR may involve nitric oxide, airway sensory fibers and mast cell-derived mediators. The effect of NO seemed to be largely restricted to the bronchial tonus, whereas neuropeptides appeared to be linked to the inflammatory response, therefore indicating that the mechanisms responsible for the changes of airway responsiveness caused by FA may be separate from those underlying its inflammatory lung effects. (c) 2005 Elsevier B.V. All rights reserved.

Dexamethasone reduces bronchial wall remodeling during pulmonary migration of Strongyloides venezuelensis larvae in rats

Strongyloidiasis is an intestinal parasitosis with an obligatory pulmonary cycle. A Th2-type immune response is induced and amplifies the cellular response through the secretion of inflammatory mediators. Although this response has been described as being similar to asthma, airway remodeling during pulmonary migration of larvae has not yet been established. The aim of this study was to identify the occurrence of airway remodeling during Strongyloides venezuelensis (S. v.) infection and to determine the ability of dexamethasone treatment to interfere with the mechanisms involved in this process. Rats were inoculated with 9,000 S. v. larvae, treated with dexamethasone (2 mg/kg) and killed at 1, 3, 5, 7, 14 and 21 days. Morphological and morphometric analyzes with routine stains and immunohistochemistry were conducted, and some inflammatory mediators were evaluated using ELISA. Goblet cell hyperplasia and increased bronchiolar thickness, characterized by edema, neovascularization, inflammatory infiltrate, collagen deposition and enlargement of the smooth muscle cell layer were observed. VEGF, IL1-beta and IL-4 levels were elevated throughout the course of the infection. The morphological findings and the immunomodulatory response to the infection were drastically reduced in dexamethasone-treated rats. The pulmonary migration of S. venezuelensis larvae produced a transitory, but significant amount of airway remodeling with a slight residual bronchiolar fibrosis. The exact mechanisms involved in this process require further study. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Effects of lung recruitment maneuvers on splanchnic organ perfusion during endotoxin-induced pulmonary arterial hypertension

Lung recruitment maneuvers (RMs), used to reopen atelectatic lung units and to improve oxygenation during mechanical ventilation, may result in hemodynamic impairment. We hypothesize that pulmonary arterial hypertension aggravates the consequences of RMs in the splanchnic circulation. Twelve anesthetized pigs underwent laparotomy and prolonged postoperative ventilation. Systemic, regional, and organ blood flows were monitored. After 6 h (= baseline), a recruitment maneuver was performed with sustained inflation of the lungs. Thereafter, the pigs were randomly assigned to group C (control, n = 6) or group E with endotoxin-induced pulmonary arterial hypertension (n = 6). Endotoxemia resulted in a normotensive and hyperdynamic state and a deterioration of the oxygenation index by 33%. The RM was then repeated in both groups. Pulmonary artery pressure increased during lipopolysaccharide infusion from 17 �� 2 mmHg (mean �� SD) to 31 �� 10 mmHg and remained unchanged in controls (P < 0.05). During endotoxemia, RM decreased aortic pulse pressure from 37 �� 14 mmHg to 27 �� 13 mmHg (mean �� SD, P = 0.024). The blood flows of the renal artery, hepatic artery, celiac trunk, superior mesenteric artery, and portal vein decreased to 71% �� 21%, 69% �� 20%, 76% �� 16%, 79% �� 18%, and 81% �� 12%, respectively, of baseline flows before RM (P < 0.05 all). Organ perfusion of kidney cortex, kidney medulla, liver, and jejunal mucosa in group E decreased to 65% �� 19%, 77% �� 13%, 66% �� 26%, and 71% �� 12%, respectively, of baseline flows (P < 0.05 all). The corresponding recovery to at least 90% of baseline regional blood flow and organ perfusion lasted 1 to 5 min. Importantly, the decreases in regional blood flows and organ perfusion and the time to recovery of these flows did not differ from the controls. In conclusion, lipopolysaccharide-induced pulmonary arterial hypertension does not aggravate the RM-induced significant but short-lasting decreases in systemic, regional, and organ blood flows.

Perforation of the pulmonary artery by a bronchial wall stent

Implantation of stents into the bronchial walls is a newly developed method to treat lung emphysema, which is now being tested clinically. During this procedure, a bronchoscope carrying a Doppler ultrasonography head is placed into a segmental bronchus and the blood vessels running in parallel to the bronchus are localized. Once a safe location without blood vessels is found, the bronchial wall is perforated and a stent is placed within the wall to improve the expiratory volume of these "bypasses" to the adjacent lung parenchyma. We observed a fatal complication with this method in a 60-year-old man. The bronchial wall and the pulmonary artery were perforated by one of the stents inducing massive bleeding, which could not be stopped. The patient died due to aspiration of blood in combination with massive loss of blood. The general risk to perforate the pulmonary artery during this procedure cannot be estimated from this single observation but should be considered regarding the legal and clinical aspects.

Aorto-bronchial and aorto-pulmonary fistulation after thoracic endovascular aortic repair: an analysis from the European Registry of Endovascular Aortic Repair Complications

OBJECTIVES To learn upon incidence, underlying mechanisms and effectiveness of treatment strategies in patients with central airway and pulmonary parenchymal aorto-bronchial fistulation after thoracic endovascular aortic repair (TEVAR). METHODS Analysis of an international multicentre registry (European Registry of Endovascular Aortic Repair Complications) between 2001 and 2012 with a total caseload of 4680 TEVAR procedures (14 centres). RESULTS Twenty-six patients with a median age of 70 years (interquartile range: 60-77) (35% female) were identified. The incidence of either central airway (aorto-bronchial) or pulmonary parenchymal (aorto-pulmonary) fistulation (ABPF) in the entire cohort after TEVAR in the study period was 0.56% (central airway 58%, peripheral parenchymal 42%). Atherosclerotic aneurysm formation was the leading indication for TEVAR in 15 patients (58%). The incidence of primary endoleaks after initial TEVAR was n = 10 (38%), of these 80% were either type I or type III endoleaks. Fourteen patients (54%) developed central left bronchial tree lesions, 11 patients (42%) pulmonary parenchymal lesions and 1 patient (4%) developed a tracheal lesion. The recognized mechanism of ABPF was external compression of the bronchial tree in 13 patients (50%), the majority being due to endoleak formation, further ischaemia due to extensive coverage of bronchial feeding arteries in 3 patients (12%). Inflammation and graft erosion accounted for 4 patients (30%) each. Cumulative survival during the entire study period was 39%. Among deaths, 71% were attributed to ABPF. There was no difference in survival in patients having either central airway or pulmonary parenchymal ABPF (33 vs 45%, log-rank P = 0.55). Survival with a radical surgical approach was significantly better when compared with any other treatment strategy in terms of overall survival (63 vs 32% and 63 vs 21% at 1 and 2 years, respectively), as well as in terms of fistula-related survival (63 vs 43% and 63 vs 43% at 1 and 2 years, respectively). CONCLUSIONS ABPF is a rare but highly lethal complication after TEVAR. The leading mechanism behind ABPF seems to be a continuing external compression of either the bronchial tree or left upper lobe parenchyma. In this setting, persisting or newly developing endoleak formation seems to play a crucial role. Prognosis does not differ in patients with central airway or pulmonary parenchymal fistulation. Radical bronchial or pulmonary parenchymal repair in combination with stent graft removal and aortic reconstruction seems to be the most durable treatment strategy.

Ventilation/perfusion SPECT/CT in patients with pulmonary emphysema. Evaluation of software-based analysing

UNLABELLED The purpose of this study was to evaluate the reproducibility of a new software based analysing system for ventilation/perfusion single-photon emission computed tomography/computed tomography (V/P SPECT/CT) in patients with pulmonary emphysema and to compare it to the visual interpretation. PATIENTS, MATERIAL AND METHODS 19 patients (mean age: 68.1 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. Data were analysed by two independent observers in visual interpretation (VI) and by software based analysis system (SBAS). SBAS PMOD version 3.4 (Technologies Ltd, Zurich, Switzerland) was used to assess counts and volume per lung lobe/per lung and to calculate the count density per lung, lobe ratio of counts and ratio of count density. VI was performed using a visual scale to assess the mean counts per lung lobe. Interobserver variability and association for SBAS and VI were analysed using Spearman's rho correlation coefficient. RESULTS Interobserver agreement correlated highly in perfusion (rho: 0.982, 0.957, 0.90, 0.979) and ventilation (rho: 0.972, 0.924, 0.941, 0.936) for count/count density per lobe and ratio of counts/count density in SBAS. Interobserver agreement correlated clearly for perfusion (rho: 0.655) and weakly for ventilation (rho: 0.458) in VI. CONCLUSIONS SBAS provides more reproducible measures than VI for the relative tracer uptake in V/P SPECT/CTs in patients with pulmonary emphysema. However, SBAS has to be improved for routine clinical use.

Ventilation/perfusion SPECT or SPECT/CT for lung function imaging in patients with pulmonary emphysema?

PURPOSE To evaluate the utility of attenuation correction (AC) of V/P SPECT images for patients with pulmonary emphysema. MATERIALS AND METHODS Twenty-one patients (mean age 67.6��years) with pulmonary emphysema who underwent V/P SPECT/CT were included. AC/non-AC V/P SPECT images were compared visually and semiquantitatively. Visual comparison of AC/non-AC images was based on a 5-point likert scale. Semiquantitative comparison assessed absolute counts per lung (aCpLu) and lung lobe (aCpLo) for AC/non-AC images using software-based analysis; percentage counts (PC��=��(aCpLo/aCpLu)������100) were calculated. Correlation between AC/non-AC V/P SPECT images was analyzed using Spearman's rho correlation coefficient; differences were tested for significance with the Wilcoxon rank sum test. RESULTS Visual analysis revealed high conformity for AC and non-AC V/P SPECT images. Semiquantitative analysis of PC in AC/non-AC images had an excellent correlation and showed no significant differences in perfusion (����=��0.986) or ventilation (����=��0.979, p��=��0.809) SPECT/CT images. CONCLUSION AC of V/P SPECT images for lung lobe-based function imaging in patients with pulmonary emphysema do not improve visual or semiquantitative image analysis.

Synthesis and toxicological evaluation of a chitosan���L���leucine conjugate for pulmonary drug delivery applications

Herein are reported the synthesis of a conjugate of chitosan with L-leucine, the preparation of nanoparticles from both chitosan and the conjugate for use in pulmonary drug delivery, and the in vitro evaluation of toxicity and inflammatory effects of both the polymers and their nanoparticles on the bronchial epithelial cell line, BEAS-2B. The nanoparticles, successfully prepared both from chitosan and the conjugate, had a diameter in the range of 10���30 nm. The polymers and their nanoparticles were tested for their effects on cell viability by MTT assay, on trans-epithelial permeability by using sodium fluorescein as a fluid phase marker, and on IL-8 secretion by ELISA. The conjugate nanoparticles had a low overall toxicity (IC50 = 2 mg/mL following 48 h exposure; no induction of IL-8 release at 0.5 mg/mL concentration), suggesting that they may be safe for pulmonary drug delivery applications.