Cell and tissue adaptation in the pulmonary autograft in a large animal model of the Ross procedure
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ABSTRACT:
PROVIDER: PRJNA1123741 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29401870.fastq.gz | Fastqsanger.gz | |||
| SRR29401871.fastq.gz | Fastqsanger.gz | |||
| SRR29401872.fastq.gz | Fastqsanger.gz | |||
| SRR29401873.fastq.gz | Fastqsanger.gz | |||
| SRR29401874.fastq.gz | Fastqsanger.gz |
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Project description:In the Ross procedure, a patient's pulmonary valve is transplanted into aortic position. Reoperation is needed in many cases due to failure through dilatation of the pulmonary autograft. To further understand the failure mechanisms, gene expression profiling of the autograft tissue was performed and compared to control aortic and pulmonary sinus tissue though bulk RNA-seq. Notable results include the upregulation of inflammatory pathways and genes coding for proteins important for the structural integrity of the tissue, such as extracellular matrix proteins, collagenases and elastases.
2024-06-14 | GSE269818 | GEO
Project description:Quadricuspid pulmonary valve is an uncommon congenital anomaly. Little information is available about use of nonstandard pulmonary valves for the Ross procedure. Here we report the use of a symmetric quadricuspid pulmonary valve as a Ross autograft, including technical implantation details, and demonstrate an acceptable 1-year outcome.
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Project description:Pulmonary fibrosis is a progressive interstitial lung disease characterised by a progressive loss of lung function. It can occur as a result of occupational or medical exposures, genetic defects, trauma or acute lung injury leading to fibroproliferative acute respiratory distress syndrome, or it can occur in an idiopathic manner. The pathogenesis of each form of pulmonary fibrosis remains unclear. A variety of animal models have been developed to better understand the pathogenesis of pulmonary fibrosis. It has been shown that animal models of pulmonary fibrosis rely heavily on severe adverse effects induced by a variety of drugs, such as bleomycin, amiodarone, lipopolysaccharide and silica. The construction of animal models plays a key role in our understanding of the molecular mechanisms underlying the pathogenesis of PF, in outlining patient-specific pathology and in developing therapeutic strategies. However, the differences between models of pulmonary fibrosis induced by different drugs have rarely been investigated. Therefore, in this paper we performed single-cell sequencing analysis of animal models constructed from four drugs. The characteristics of the changes in the number of epithelial cells and macrophages and their functional enrichment in each model were summarised, and it was deduced that the model induced by lipopolysaccharide was mainly focused on the inflammatory damage stage of pulmonary fibrosis, the model induced by amiodarone on the regeneration stage of persistent failure, and the model induced by bleomycin and silica on the fibrotic stage of pulmonary fibrosis.
2025-04-30 | GSE295463 | GEO
Project description:A retrospective cohort study was conducted in which 129 adult patients with bicuspid aortic valves underwent the Ross procedure with either a standard root inclusion technique or a modified technique whereby the pulmonary autograft is wrapped in a vascular conduit. Primary outcomes were survival and the need for pulmonary autograft reintervention. Competing risk analysis demonstrated the wrapped technique reduced pulmonary autograft reintervention.
| S-EPMC8690298 | biostudies-literature
Project description:BackgroundPulmonary autograft reinforcement to prevent dilatation and subsequent neo-aortic valve regurgitation has been reported; however, data on long-term function of the neo-aortic valve after this modified Ross procedure are lacking. Our objective here was to assess long-term outcomes of the modified Ross procedure with autograft reinforcement using the reimplantation technique.PatientsThe outcomes of 61 consecutive patients managed using the Dacron-conduit reinforced Ross procedure between 2009 and 2021 were reviewed. Most patients had a unicuspid or bicuspid aortic valve (n = 52; 85%), predominant aortic valve regurgitation (n = 42; 77%), and >30 mm dilatation of the ascending aorta (n = 33; 54%). A prior aortic valve procedure was noted in 47 patients (77%) patients, including 38 (62%) with surgical repair and 9 (15%) with balloon dilatation. The pulmonary autograft was reimplanted within a Dacron conduit with a median diameter of 25.6 mm (range, 20-30 mm) using the David valve-sparing aortic root replacement technique.ResultsAll patients survived. The median age at surgery was 16.8 years (range, 6-38 years). Neo-aortic valve replacement was required in 3 patients (4.9%; 95% CI, 0.34%- 12.7%) because of infective endocarditis, left ventricular false aneurysm, and leaflet perforation, respectively; the repeat procedure was done early in 2 of these patients (2 of 61; 3%). Six patients required right ventricular outflow conduit replacement, 5 by surgery and 1 percutaneously. The median duration of follow-up was 90 months (range, 10-124 months). The 5- and 10-year rates of reintervention-free survival were 84.3% (95% CI, 74%-95%) and 81.6% (95% CI, 72%-93%), respectively, and 5-year survival without aortic reintervention was 94.5% (95% CI, 88%-100%), with little change at 10 years. No patients experienced deterioration of initial neo-aortic valve function (ie, regurgitation or stenosis).ConclusionsAutograft reinforcement using the reimplantation technique allowed expansion of Ross procedure indications to all patients requiring aortic valve replacement and prevented neo-aortic root dilatation. Failures were uncommon. Long-term follow-up data showed stable neo-aortic valve function.
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Project description:The Ross procedure using the inclusion technique with anticommissural plication (ACP) is associated with excellent valve hemodynamics and favorable leaflet kinematics. The objective was to evaluate individual pulmonary cusp's biomechanics and fluttering by including coronary flow in the Ross procedure using an ex vivo three-dimensional-printed heart simulator. Ten porcine and five human pulmonary autografts were harvested from a meat abattoir and heart transplant patients. Five porcine autografts without reinforcement served as controls. The other autografts were prepared using the inclusion technique with and without ACP (ACP and NACP). Hemodynamic and high-speed videography data were measured using the ex vivo heart simulator. Although porcine autografts showed similar leaflet rapid opening and closing mean velocities, human ACP compared to NACP autografts demonstrated lower leaflet rapid opening mean velocity in the right (p = 0.02) and left coronary cusps (p = 0.003). The porcine and human autograft leaflet rapid opening and closing mean velocities were similar in all three cusps. Porcine autografts showed similar leaflet flutter frequencies in the left (p = 0.3) and noncoronary cusps (p = 0.4), but porcine NACP autografts versus controls demonstrated higher leaflet flutter frequency in the right coronary cusp (p = 0.05). The human NACP versus ACP autografts showed higher flutter frequency in the noncoronary cusp (p = 0.02). The leaflet flutter amplitudes were similar in all three cusps in both porcine and human autografts. The ACP compared to NACP autografts in the Ross procedure was associated with more favorable leaflet kinematics. These results may translate to the improved long-term durability of the pulmonary autografts.
| S-EPMC9445321 | biostudies-literature
Project description:Background: Chronic obstructive pulmonary disease (COPD) is a serious chronic disease of the airways that affects many people worldwide and have limited treatment options. While small animal models provide a platform for therapeutic investigations into COPD, their deficiencies continue to impede clinical translation. Alternatively, as a large animal model, sheep have a respiratory system anatomically and physiologically similar to that of humans, encouraging their use in airway disease research. The aim of this study was to better understand disease pathology in a large animal (sheep) experimental model of COPD. Methods: COPD was induced in sheep following lung exposure to porcine elastase (PE) and repeated weekly lung exposures to lipopolysaccharide (LPS) over a period of 8 weeks. Bronchoalveolar fluid and blood samples were collected for immune analyses. Lung function was assessed and lung tissues were collected for histopathology and RNA sequencing. Results: Lung neutrophil levels were elevated in response to repeated airway exposure to PE/LPS, accompanied by a significant decline in ventilation over time. Histological evidence of COPD-like disease changes included chronic inflammation with increased airway and tissue inflammation scores, together with significantly larger airway wall area measures, increased connective tissue deposition and dysregulated gene expression. Conclusions: These studies demonstrate sustained chronic airway inflammation and pathophysiological lung changes in a sheep model of COPD, providing many similarities to that seen in COPD patients. This work opens a pathway for future translational studies using this unique large animal model of COPD, which will serve to bridge the gap between smaller animal models and humans.
2023-12-31 | GSE242416 | GEO
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