Project description:Vascular bio-scaffolds produced from decellularized tissue offer a promising material for treatment of several types of cardiovascular diseases. These materials have the potential to maintain the functional properties of the extracellular matrix (ECM), and allow for growth and remodeling in vivo. The most commonly used methods for decellularization are based on chemicals and enzymes combinations, which often damage the ECM and cause cytotoxic effects in vivo. Mild methods involving pressurized CO2-ethanol (EtOH)-based fluids, in a supercritical or near supercritical state, have been studied for decellularization of cardiovascular tissue, but results are controversial. Moreover, data are lacking on the amount and type of lipids remaining in the tissue. Here we show that pressurized CO2-EtOH-H2O fluids (average molar composition, ΧCO2 0.91) yielded close to complete removal of lipids from porcine pulmonary arteries, including a notably decrease of pro-inflammatory fatty acids. Pressurized CO2-limonene fluids (ΧCO2 0.88) and neat supercritical CO2 (scCO2) achieved the removal of 90% of triacylglycerides. Moreover, treatment of tissue with pressurized CO2-limonene followed by enzyme treatment, resulted in efficient DNA removal. The structure of elastic fibers was preserved after pressurized treatment, regardless solvent composition. In conclusion, pressurized CO2-ethanol fluids offer an efficient tool for delipidation in bio-scaffold production, while pressurized CO2-limonene fluids facilitate subsequent enzymatic removal of DNA.
Project description:This study investigated whether dilated bronchial arteries are associated with reperfusion pulmonary edema in patients with chronic thromboembolic pulmonary hypertension. Results showed that the extent of enlarged bronchial arteries was not associated with the development of reperfusion pulmonary edema, whereas the residual pulmonary hypertension had a significant association.
Project description:The aim of our study was to determine the prevalence of anatomical variants of bronchial arteries using computed tomographic angiography in a population of northeastern Mexico. An observational, transversal, descriptive, comparative, retrospective study was performed using 139 imaging studies of Mexican patients in which we evaluated the following parameters from the left and right bronchial arteries: artery origin, branching pattern, arterial ostium, vertebral level of origin, diameter, and mediastinal trajectory. The anatomies of the bronchial arteries were similar in both genders, except distribution for vertebral origin level (p 0.006) and the diameter (p 0.013). Left and right arteries were similar, except for the mediastinal trajectory in reference to the esophagus (p < 0.001) as well as the arterial diameter (p < 0.001) and lumen diameter.
Project description:ObjectiveTo evaluate the clinical value of using monochromatic images in spectral CT pulmonary angiography to improve image quality of bronchial arteries.MethodsWe retrospectively analyzed the chest CT images of 38 patients who underwent contrast-enhanced spectral CT. These images included a set of 140kVp polychromatic images and the default 70keV monochromatic images. Using the standard Gemstone Spectral Imaging (GSI) viewer on an advanced workstation (AW4.6,GE Healthcare), an optimal energy level (in keV) for obtaining the best contrast-to-noise ratio (CNR) for the artery could be automatically obtained. The signal-to-noise ratio (SNR), CNR and objective image quality score (1-5) for these 3 image sets (140kVp, 70keV and optimal energy level) were obtained and, statistically compared. The image quality score consistency between the two observers was also evaluated using Kappa test.ResultsThe optimal energy levels for obtaining the best CNR were 62.58±2.74keV.SNR and CNR from the 140kVp polychromatic, 70keV and optimal keV monochromatic images were (16.44±5.85, 13.24±5.52), (20.79±7.45, 16.69±6.27) and (24.9±9.91, 20.53±8.46), respectively. The corresponding subjective image quality scores were 1.97±0.82, 3.24±0.75, and 4.47±0.60. SNR, CNR and subjective scores had significant difference among groups (all p<0.001). The optimal keV monochromatic images were superior to the 70keV monochromatic and 140kVp polychromatic images, and there was high agreement between the two observers on image quality score (kappa>0.80).ConclusionsVirtual monochromatic images at approximately 63keV in dual-energy spectral CT pulmonary angiography yielded the best CNR and highest diagnostic confidence for imaging bronchial arteries.
Project description:Changes in structure and function of small muscular arteries play a major role in the pathophysiology of pulmonary hypertension, a burgeoning public health challenge. Improved anatomically mimetic in vitro models of these microvessels are urgently needed because nonhuman vessels and previous models do not accurately recapitulate the microenvironment and architecture of the human microvascular wall. Here, we describe parallel biofabrication of photopatterned self-rolled biomimetic pulmonary arterial microvessels of tunable size and infrastructure. These microvessels feature anatomically accurate layering and patterning of aligned human smooth muscle cells, extracellular matrix, and endothelial cells and exhibit notable increases in endothelial longevity and nitric oxide production. Computational image processing yielded high-resolution 3D perspectives of cells and proteins. Our studies provide a new paradigm for engineering multicellular tissues with precise 3D spatial positioning of multiple constituents in planar moieties, providing a biomimetic platform for investigation of microvascular pathobiology in human disease.
Project description:The biomechanical properties of the major pulmonary arteries play critical roles in normal physiology as well as in diverse pathophysiologies and clinical interventions. Importantly, advances in medical imaging enable simulations of pulmonary hemodynamics, but such models cannot reach their full potential until they are informed with region-specific material properties. In this paper, we present passive and active biaxial biomechanical data for the right and left main pulmonary arteries from wild-type mice. We also evaluate the suitability of a four-fiber family constitutive model as a descriptor of the passive behavior. Despite regional differences in size, the biaxial mechanical properties, including passive stiffness and elastic energy storage, the biaxial wall stresses at in vivo pressures, and the overall contractile capacity in response to smooth muscle cell stimulation under in vivo conditions are remarkably similar between the right and left branches. The proposed methods and results can serve as baseline protocols and measurements for future biaxial experiments on murine models of pulmonary pathologies, and the constitutive model can inform computational models of normal pulmonary growth and remodeling. Our use of consistent experimental protocols and data analyses can also facilitate comparative studies in health and disease across the systemic and pulmonary circulations as well as studies seeking to understand remodeling in surgeries such as the Fontan procedure, which involves different types of vessels.
Project description:BackgroundThe present study investigated whether highly vascularized bronchial arteries affect the intraoperative blood loss and the operative time of video-assisted thoracic surgery (VATS) lobectomy for patients with non-small cell lung cancer.Methods: We retrospectively collected data on consecutive pathological stage I to IIIA non-small cell lung cancer patients who underwent VATS lobectomy with systematic lymph node dissection between January 2017 and December 2019. Patients were divided into the following two groups according to bronchial artery diameters on preoperative enhanced contrast computed tomography (CT) findings: ≤2 and >2 mm groups.ResultsAmong the 175 patients enrolled, risk factors for intraoperative blood loss >50 mL were being male (P=0.005), a history of smoking (P=0.01), percent forced expiratory volume in 1 s (FEV1.0%) <70% (P=0.012), squamous cell carcinoma (P=0.049), and a bronchial artery diameter >2.0 mm (P<0.001) in the unadjusted analysis, and a bronchial artery diameter >2.0 mm (P<0.001) in the multivariable analysis. Risk factors for an operative time >200 min were being male (P<0.001), a history of smoking (P=0.007), FEV1.0% <70% (P=0.011), squamous cell carcinoma (P=0.046), a bronchial artery diameter >2.0 mm (P<0.001), and experience of surgeon <10 years (P=0.011) in the unadjusted analysis, and being male (P=0.047), a bronchial artery diameter >2.0 mm (P=0.024), and experience of surgeon <10 years (P=0.047) in the multivariable analysis.ConclusionsBronchial artery diameter was the most important risk factor of intraoperative bleeding and prolonged operative time during VATS lobectomy.
Project description:AimsChemokine CXCL12 (stromal derived factor 1: SDF1) has been shown to play important roles in various processes of cardiovascular development. In recent avian studies, CXCL12 signalling has been implicated in guidance of cardiac neural crest cells for their participation in the development of outflow tract and cardiac septum. The goal of this study is to investigate the extent to which CXCL12 signalling contribute to the development of aortic arch and pulmonary arteries in mammals.Methods and resultsNovel Cxcl12-LacZ reporter and conditional alleles were generated. Using whole mount X-gal staining with the reporter allele and vascular casting techniques, we show that the domain branching pattern of pulmonary arteries in Cxcl12-null mice is completely disrupted and discordant with that of pulmonary veins and airways. Cxcl12-null mice also displayed abnormal and superfluous arterial branches from the aortic arch. The early steps of pharyngeal arch remodelling in Cxcl12-null mice appeared to be unaffected, but vertebral arteries were often missing and prominent aberrant arteries were present parallel to carotid arteries or trachea, similar to aberrant vertebral artery or thyroid ima artery, respectively. Analysis with computed tomography not only confirmed the results from vascular casting studies but also identified abnormal systemic arterial supply to lungs in the Cxcl12-null mice. Tie2-Cre mediated Cxcr4 deletion phenocopied the Cxcl12-null phenotypes, indicating that CXCR4 is the primary receptor for arterial patterning, whereas Cxcl12 or Cxcr4 deletion by Wnt1-Cre did not affect aortic arch patterning.ConclusionCXCL12-CXCR4 signalling is essential for the correct patterning of aortic arches and pulmonary arteries during development. Superfluous arteries in Cxcl12-null lungs and the aortic arch infer a role of CXCL12 in protecting arteries from uncontrolled sprouting during development of the arterial system.
Project description:Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation, small airway remodeling, and emphysema. Airway remodeling in patients with COPD involves both the airway epithelium and the subepithelial extracellular matrix (ECM). However, it is currently unknown how epithelial remodeling in COPD airways depends on the relative influence from inherent defects in the epithelial cells and alterations in the ECM. To address this, we analyzed global gene expression in COPD human bronchial epithelial cells (HBEC) and normal HBEC after repopulation on decellularized bronchial scaffolds derived from patients with COPD or donors without COPD. COPD HBEC grown on bronchial scaffolds showed an impaired ability to initiate ciliated-cell differentiation, which was evident on all scaffolds regardless of their origin. In addition, although normal HBEC were less affected by the disease state of the bronchial scaffolds, COPD HBEC showed a gene expression pattern indicating increased proliferation and a retained basal-cell phenotype when grown on COPD bronchial scaffolds compared with normal bronchial scaffolds. By using mass spectrometry, we identified 13 matrisome proteins as being differentially abundant between COPD bronchial scaffolds and normal bronchial scaffolds. These observations are consistent with COPD pathology and suggest that both epithelial cells and the ECM contribute to epithelial-cell remodeling in COPD airways.