Clinical, Histological, and Profibrotic Extracellular Matrix Protein Changes in a Model of Tracheal Stenosis Induced by Cervical Tracheal Autotransplantation.

BACKGROUND: Tracheal stenosis (TS) is a complication of prolonged intubation, tracheotomy, and tracheal surgery that compromises the vascular supply. Animal models are essential for studying its pathophysiology and the effect of interventions. OBJECTIVE: To establish a TS model in rats secondary to tracheal autotransplantation with a graft submerged in bleomycin (Atx-Bleo). Additionally, to evaluate the clinical and histological changes, as well as the expression of newly formed collagen (NFC), isoforms of transforming growth factor beta (TGFß), fibronectin (FN), elastin (ELN), integrin ß1 (ITGß1), and matrix metalloproteinase 1 (MMP1) in TS. METHODS: Twenty Wistar rats were divided into three groups: group I (n = 20) control; group II (n = 10) end-to-end anastomosis of the trachea (tracheoplasty); and group III (n = 10) Atx-Bleo. The animals were evaluated clinically, tomographically, macroscopically, morphometrically, and microscopically. NFC deposition, and the expression of profibrotic and antifibrotic proteins were evaluated in tracheal scars. RESULTS: All animals survived the surgical procedure and the study period. Compared with the other study groups, the Atx-Bleo group developed TS and fibrosis, exhibited higher expression of NFC, TGFß1, TGFß2, FN, ELN, and ITGß1, and mild expression of TGFß3 and MMP1 (p < 0.005; analysis of variance, Dunnett and Tukey tests). CONCLUSION: Atx-Bleo in TS model rats produces tomographic and histological changes, and induces the upregulation of profibrotic proteins (TGFß1, TGFß2, collagen, FN, ELN, ITGß1) and downregulation of antifibrotic proteins (TGFß3, MMP1). Therefore, this model may be used to test new pharmacological treatments for reversing or preventing TS, and conduct basic studies regarding its pathophysiology.

Expression of Claudin-4 in Lung Ischemia-Reperfusion Injury in Experimental Lung Transplantation.

OBJECTIVE: To assess the presence of CLDN4 in bronchoalveolar lavage fluid (BALF) and pulmonary tissue as an early indicator of LIRI and its relationship with changes in pulmonary physiology, edema formation and histology in an experimental porcine model of LTx with CIT of 50 min or 6 h. METHODS: In 12 pigs, LIRI was produced by: group I (n = 6) LTx with 50 min of CIT (LTx-50 min-CIT); and group II (n = 6) LTx with 6 h of CIT (LTx-6h-CIT). The lung function, edema formation, macroscopic and microscopic changes were assessed. CLDN4 expression in BALF and pulmonary tissue were determined. RESULTS: Both groups presented similar clinical, edema, and histological damage, as well as similar expression of CLDN4 in BALF and tissue (p > 0.05, RM-ANOVA). CONCLUSION: CLDN4 expressed in BALF and the pulmonary tissue during the first 5 h within 72 h of the PGD window are not associated by the deterioration of lung function, edema and lung histological injury, in LTx with CIT 50 min or 6 h, CLDN4 does not seem to be a valuable indicator of LIRI.

Treatment with Hyaluronic Acid and Collagen-Polyvinylpyrrolidone Improves Extracellular Matrix Assembly for Scarring after Tracheal Resection.

Treatment of tracheal stenosis is occasionally performed in combination with wound healing modulators to manipulate new extracellular matrix (ECM) formation and prevent fibrosis. Hyaluronic acid (HA) and collagen-polyvinylpyrrolidone (collagen-PVP) decrease fibrosis in experimental tracheal healing. However, they have not been used clinically as their effect on ECM components, which modify tracheal scarring, has not been described. Objective. To evaluate the effect of the application of HA, collagen-PVP, a mixture of HA and collagen-PVP (HA+collagen-PVP), and mitomycin C on the expression of decorin, matrix metalloproteinase 1 (MMP1), and MMP9, as well as the type of collagen and deposits formed in the scar after resection and end-to-end anastomosis (REEA) of the cervical trachea using an experimental model. Materials and Methods. Thirty dogs underwent REEA of the cervical trachea and were treated with different wound healing modulators: group I (n = 6), control; group II (n = 6), HA; group III (n = 6), collagen-PVP; group IV (n = 6), HA+collagen-PVP; and group V (n = 6), mitomycin C. The dogs were evaluated clinically and endoscopically for 4 weeks. Subsequently, macroscopic and microscopic changes, expression of ECM proteins, and collagen deposition in tracheal scars were analysed. Results. Groups II, III, and IV showed reduced endoscopic, macroscopic, and microscopic inflammation, improved neovascularization, high decorin expression (p < 0.01, analysis of variance (ANOVA)), and moderate expression of MMP1 (p < 0.003, ANOVA) and type I and III collagen (p < 0.05, Kruskal-Wallis). Groups IV and V developed fewer collagen deposits (p < 0.001, ANOVA). Conclusion. Treatment with HA and collagen-PVP improved post-REEA healing by increasing neovascularization, stimulating the expression of decorin, and regulating the expression of MMP1, as well as type I and III collagen and their deposition.