Changes in the levels of free sialic acid during ex vivo lung perfusion do not correlate with pulmonary function. Experimental model.

BACKGROUND: Ex vivo lung perfusion (EVLP) constitutes a tool with great research potential due to its advantages over in vivo and in vitro models. Despite its important contribution to lung reconditioning, this technique has the disadvantage of incurring high costs and can induce pulmonary endothelial injury through perfusion and ventilation. The pulmonary endothelium is made up of endothelial glycocalyx (EG), a coating of proteoglycans (PG) on the luminal surface. PGs are glycoproteins linked to terminal sialic acids (Sia) that can affect homeostasis with responses leading to edema formation. This study evaluated the effect of two ex vivo perfusion solutions on lung function and endothelial injury. METHODS: We divided ten landrace swine into two groups and subjected them to EVLP for 120 min: Group I (n = 5) was perfused with Steen® solution, and Group II (n = 5) was perfused with low-potassium dextran-albumin solution. Ventilatory mechanics, histology, gravimetry, and sialic acid concentrations were evaluated. RESULTS: Both groups showed changes in pulmonary vascular resistance and ventilatory mechanics (p < 0.05, Student's t-test). In addition, the lung injury severity score was better in Group I than in Group II (p < 0.05, Mann-Whitney U); and both groups exhibited a significant increase in Sia concentrations in the perfusate (p < 0.05 t-Student) and Sia immunohistochemical expression. CONCLUSIONS: Sia, as a product of EG disruption during EVLP, was found in all samples obtained in the system; however, the changes in its concentration showed no apparent correlation with lung function.

Biomolecules resveratrol + coenzyme Q10 recover the cell state of human mesenchymal stem cells after 1-methyl-4-phenylpyridinium-induced damage and improve proliferation and neural differentiation.

Neurodegenerative disorders are a critical affection with a high incidence around the world. Currently, there are no effective treatments to solve this problem. However, the application of mesenchymal stem cells (MSCs) and antioxidants in neurodegenerative diseases has shown to be a promising tool due to their multiple therapeutic effects. This work aimed to evaluate the effects of a combination of resveratrol (RSV) and coenzyme Q10 (CoQ10) on the proliferation and differentiation of MSC and the protector effects in induced damage. To characterize the MSCs, we performed flow cytometry, protocols of cellular differentiation, and immunocytochemistry analysis. The impact of RSV + CoQ10 in proliferation was evaluated by supplementing 2.5 and 10 µM of RSV + CoQ10 in a cellular kinetic for 14 days. Cell viability and lactate dehydrogenase levels (LDH) were also analyzed. The protective effect of RSV + CoQ10 was assessed by supplementing the treatment to damaged MSCs by 1-methyl-4-phenylpyridinium (MPP+); cellular viability, LDH, and reactive oxygen species (ROS) were evaluated.. MSCs expressed the surface markers CD44, CD73, CD90, and CD105 and showed multipotential ability. The combination of RSV + CoQ10 increased the proliferation potential and cell viability and decreased LDH levels. In addition, it reverted the effect of MPP+-induced damage in MSCs to enhance cell viability and decrease LDH and ROS. Finally, RSV + CoQ10 promoted the differentiation of neural progenitors. The combination of RSV + CoQ10 represents a potential treatment to improve MSCs capacities and protect against neurodegenerative damage.

Endothelin-Converting Enzyme 1 and Vascular Endothelial Growth Factor as Potential Biomarkers during Ex Vivo Lung Perfusion with Prolonged Hypothermic Lung-Sparing.

Lung transplantation requires optimization of donor's organ use through ex vivo lung perfusion (EVLP) to avoid primary graft dysfunction. Biomarkers can aid in organ selection by providing early evidence of suboptimal lungs during EVLP and thus avoid high-risk transplantations. However, predictive biomarkers of pulmonary graft function such as endothelin-converting enzyme (ECE-1) and vascular endothelial growth factor (VEGF) have not been described under EVLP with standard prolonged hypothermic preservation, which are relevant in situations where lung procurement is difficult or far from the transplantation site. Therefore, this study is aimed at quantifying ECE-1 and VEGF, as well as determining their association with hemodynamic, gasometric, and mechanical ventilatory parameters in a swine model of EVLP with standard prolonged hypothermic preservation. Using a protocol with either immediate (I-) or delayed (D-) initiation of EVLP, ECE-1 levels over time were found to remain constant in both study groups (p > 0.05 RM-ANOVA), while the VEGF protein was higher after prolonged preservation, but it decreased throughout EVLP (p > 0.05 RM-ANOVA). Likewise, hemodynamic, gasometric, mechanical ventilatory, and histological parameters had a tendency to better results after 12 hours of hypothermic preservation in the delayed infusion group.

Loss of Znt8 function in diabetes mellitus: risk or benefit?

The zinc transporter 8 (ZnT8) plays an essential role in zinc homeostasis inside pancreatic ß cells, its function is related to the stabilization of insulin hexameric form. Genome-wide association studies (GWAS) have established a positive and negative relationship of ZnT8 variants with type 2 diabetes mellitus (T2DM), exposing a dual and controversial role. The first hypotheses about its role in T2DM indicated a higher risk of developing T2DM for loss of function; nevertheless, recent GWAS of ZnT8 loss-of-function mutations in humans have shown protection against T2DM. With regard to the ZnT8 role in T2DM, most studies have focused on rodent models and common high-risk variants; however, considerable differences between human and rodent models have been found and the new approaches have included lower-frequency variants as a tool to clarify gene functions, allowing a better understanding of the disease and offering possible therapeutic targets. Therefore, this review will discuss the physiological effects of the ZnT8 variants associated with a major and lower risk of T2DM, emphasizing the low- and rare-frequency variants.

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.

Effects of Pirfenidone and Collagen-Polyvinylpyrrolidone on Macroscopic and Microscopic Changes, TGF-ß1 Expression, and Collagen Deposition in an Experimental Model of Tracheal Wound Healing.

Tracheal stenosis (TS) is a fibrosis originated by prolonged inflammation and increased transforming growth factor beta 1 (TGF-ß1) expression and collagen deposition (CD) in the tracheal wound. Several wound-healing modulators (WHMs) have been used to modulate the tracheal healing process and prevent TS, but they have failed, justifying the need to evaluate alternative WHM. The pirfenidone (PFD) and collagen-polyvinylpyrrolidone (Collagen-PVP) decrease inflammation and fibrosis. This study assessed the effect of PFD administration and Collagen-PVP topical application on macroscopic and microscopic changes, TGF-ß1 expression, and CD in an experimental model of tracheal wound healing. Forty Wistar rats underwent cervical tracheoplasty, were divided into 4 groups (n = 10), and were treated with different WHM: group I, saline solution (SS); group II, Collagen-PVP; group III, mitomycin C (MMC); and group IV, 40 mg/kg PFD. Four weeks after surgery, the macroscopic and microscopic changes, in situ TGF-ß1 expression, and CD in posttracheoplasty scars were evaluated. The animals treated with Collagen-PVP and PFD developed less inflammation and fibrosis than animals in the other study groups (p < 0.05, Kruskal-Wallis) and, moreover, showed lower TGF-ß1 expression and CD than animals in group I (p < 0.05, ANOVA and Tukey's test). In conclusion, PFD and Collagen-PVP decrease inflammation, fibrosis, TGFß-1 expression, and CD in the posttracheoplasty rats' scar.

Effects of 2-methoxyestradiol on apoptosis and HIF-1α and HIF-2α expression in lung cancer cells under normoxia and hypoxia.

Hypoxic tumor cells are known to be more resistant to conventional chemotherapy and radiation than normoxic cells. However, the effects of 2-methoxyestradiol (2-ME), an anti-angiogenic, antiproliferative and pro-apoptotic drug, on hypoxic lung cancer cells are unknown. The aim of the present study was to compare the effects of 2-ME on cell growth, apoptosis, hypoxia-inducible factor 1α (HIF-1α) and HIF-2α gene and protein expression in A549 cells under normoxic and hypoxic conditions. To establish the optimal 2-ME concentration with which to carry out the apoptosis assay and to examine mRNA and protein expression of HIFs, cell growth analysis was carried out through N-hexa-methylpararosaniline staining assays in A549 cell cultures treated with one of five different 2-ME concentrations at different times under normoxic or hypoxic growth conditions. The 2-ME concentration of 10 mM at 72 h was selected to perform all further experiments. Apoptotic cells were analyzed by flow cytometry. Western blotting was used to determine HIF-1α and HIF-2α protein expression in total cell extracts. Cellular localization of HIF-1α and HIF-2α was assessed by immunocytochemistry. HIF-1α and HIF-2α gene expression was determined by real-time PCR. A significant increase in the percentage of apoptosis was observed when cells were treated with 2-ME under a normoxic but not under hypoxic conditions (p=0.006). HIF-1α and HIF-2α protein expression levels were significantly decreased in cells cultured under hypoxic conditions and treated with 2-ME (p<0.001). Furthermore, 2-ME decreased the HIF-1α and HIF-2α nuclear staining in cells cultured under hypoxia. The HIF-1α and HIF-2α mRNA levels were significantly lower when cells were exposed to 2-ME under normoxia and hypoxia. Our results suggest that 2-ME could have beneficial results when used with conventional chemotherapy in an attempt to lower the invasive and metastatic processes during cancer development due to its effects on the gene expression and protein synthesis of HIFs.

Comparison of lyophilized glutaraldehyde-preserved bovine pericardium with different vascular prostheses for use as vocal cords implants: experimental study.

This study compared the use of lyophilized glutaraldehyde-preserved bovine pericardium (LGPBP), polytetrafluoroethylene (PTFE), polyethylene terephthalate (PET), and Teflon felt (TF) as implants for vocal cords (VC) medialization and aimed to assess the endoscopic, macroscopic, and microscopic VC changes after medialization in a canine model. In 18 mongrel dogs, the right VC were medialized with LGPBP and the left were implanted as follows: Group I (n = 6): LGPBP and PTFE; Group II (n = 6): LGPBP and PET; Group III (n = 6): LGPBP and TF. Surgical handling of the implants was compared. Three months after surgery, macroscopic and microscopic changes of VC and implants were evaluated. LGPBP offered the best surgical handling (p = 0.005, Kruskal-Wallis). TF implants showed extrusion (p = 0.005, Kruskal-Wallis) and severe inflammation. All VC formed fibrous capsules around the implants; the ones developed by LGPBP implants were thinner (p = 0.001, ANOVA, Tukey). VC implanted with synthetic materials showed eosinophilic infiltration (p = 0.01, Kruskal-Wallis). We concluded that the LGPBP could be used as an implant for VC medialization because it is biocompatible, easy to handle and remove during surgical procedures, and nonabsorbable or extrudable and produces an inflammatory reaction similar to PTFE and PET.

Respiratory mechanics and plasma levels of tumor necrosis factor alpha and interleukin 6 are affected by gas humidification during mechanical ventilation in dogs.

The use of dry gases during mechanical ventilation has been associated with the risk of serious airway complications. The goal of the present study was to quantify the plasma levels of TNF-alpha and IL-6 and to determine the radiological, hemodynamic, gasometric, and microscopic changes in lung mechanics in dogs subjected to short-term mechanical ventilation with and without humidification of the inhaled gas. The experiment was conducted for 24 hours in 10 dogs divided into two groups: Group I (n = 5), mechanical ventilation with dry oxygen dispensation, and Group II (n = 5), mechanical ventilation with oxygen dispensation using a moisture chamber. Variance analysis was used. No changes in physiological, hemodynamic, or gasometric, and radiographic constants were observed. Plasma TNF-alpha levels increased in group I, reaching a maximum 24 hours after mechanical ventilation was initiated (ANOVA p = 0.77). This increase was correlated to changes in mechanical ventilation. Plasma IL-6 levels decreased at 12 hours and increased again towards the end of the study (ANOVA p>0.05). Both groups exhibited a decrease in lung compliance and functional residual capacity values, but this was more pronounced in group I. Pplat increased in group I (ANOVA p = 0.02). Inhalation of dry gas caused histological lesions in the entire respiratory tract, including pulmonary parenchyma, to a greater extent than humidified gas. Humidification of inspired gases can attenuate damage associated with mechanical ventilation.

Pericardio bovino tratado con glutaraldehído y liofilizado como materiales para la medialización de cuerdas vocales en modelo animal / Glutaraldehyde-preserved and lyophilized bovine pericardium as materials for medialization of the vocal folds in an animal model

Introducción: El pericardio bovino tratado con glutaraldehído (PBTG) y el pericardio bovino tratado con glutaraldehído liofilizado (PBTGL)ha sido utilizado exitosamente en la reparación de varios defectos anatómicos, pero su eficacia y seguridad como implantes de cuerdas vocales (CV) no se ha descrito. Objetivo: Evaluar la utilidad del PBTG y PBTGL como material para la medialización tiroplástica y valorar los cambios endoscópicos, macroscópicos y microscópicos de las CV posmedialización en un modelo experimental canino. Material y métodos: En 12 perros mestizos, se medializó la CV derecha con pericardio y la izquierda con politetrafluoroetileno (PTFE). Grupo i (n=6): PBTG, y Grupo ii (n=6): PBTGL. Se comparó el manejo quirúrgico de los implantes. Los animales se valoraron clínica y endoscópicamente. Tres meses poscirugía se evaluaron macroscópica y microscópicamente las laringes. Resultados: El PBTG y PBTGL mostraron mejor manejo quirúrgico (Kruskal-Wallis, p=0,005). No se presentaron granulomas, absorción o extrusión del implante en ningún caso endoscópica ni macroscópicamente. Al final del estudio las CV medializadas con PTFE se observaron más engrosadas. Microscópicamente todas las CV formaron una cápsula fibrosa alrededor del implante y una reacción inflamatoria crónica similar, pero las implantadas con PTFE mostraron infiltrado eosinofílico (Kruskal-Wallis, p<0,05). Conclusión: El PBTG y PBTGL pueden ser utilizados para la medialización de las CV debido a que son biocompatibles, de fácil manejo quirúrgico, no se absorben, no migran, ni extruyen y producen una reacción inflamatoria similar a la del PTFE (AU)

Introduction: Glutaraldehyde-preserved bovine pericardium (GBP) and lyophilized GBP (LGBP) have been used successfully in repairing several anatomical defects, but their effectiveness and safety as implants to vocal cords (VC) have not been reported. Objective: The aim of this study was to evaluate the use of GBP and LGBP as materials for medialization thyroplasty, as well as to assess the endoscopic, macroscopic and microscopic VC changes after medialization in an experimental canine model. Material and methods: In 12 healthy mongrel dogs, the right VC were medialized using pericardium and the left with polytetrafluoroethylene (PTFE). Group 1 (n=6): GBP and Group 2 (n=6): LGBP. The surgical manoeuvrability of the implants was compared. The animals were evaluated clinically and endoscopically. Three months after surgery, the larynges were assessed macro- and microscopically. Results: Both GBP and LGBP implants showed better surgical manoeuvrability (Kruskal-Wallis, P=0.005). Endoscopic and macroscopic studies showed no evidence of granulomas, absorption or extrusion of the implant. At the end of the study, greater thickness was observed in VC implanted with PTFE. Microscopically, all the VC developed fibrous capsules surrounding the implants and similar chronic inflammation reaction. The VC implanted with PTFE presented eosinophilic infiltration (Kruskal-Wallis, P<0.05). Conclusion: Both GBP and LGBP can be used as implants for VC medialization because they are biocompatible, have easy surgical manoeuvrability, do not suffer absorption, migration or extrusion and produce inflammation reactions similar to those of PTFE (AU)

[Glutaraldehyde-preserved and lyophilized bovine pericardium as materials for medialization of the vocal folds in an animal model]. / Pericardio bovino tratado con glutaraldehído y liofilizado como materiales para la medialización de cuerdas vocales en modelo animal.

INTRODUCTION: Glutaraldehyde-preserved bovine pericardium (GBP) and lyophilized GBP (LGBP) have been used successfully in repairing several anatomical defects, but their effectiveness and safety as implants to vocal cords (VC) have not been reported. OBJECTIVE: The aim of this study was to evaluate the use of GBP and LGBP as materials for medialization thyroplasty, as well as to assess the endoscopic, macroscopic and microscopic VC changes after medialization in an experimental canine model. MATERIAL AND METHODS: In 12 healthy mongrel dogs, the right VC were medialized using pericardium and the left with polytetrafluoroethylene (PTFE). Group 1 (n=6): GBP and Group 2 (n=6): LGBP. The surgical manoeuvrability of the implants was compared. The animals were evaluated clinically and endoscopically. Three months after surgery, the larynges were assessed macro- and microscopically. RESULTS: Both GBP and LGBP implants showed better surgical manoeuvrability (Kruskal-Wallis, P=.005). Endoscopic and macroscopic studies showed no evidence of granulomas, absorption or extrusion of the implant. At the end of the study, greater thickness was observed in VC implanted with PTFE. Microscopically, all the VC developed fibrous capsules surrounding the implants and similar chronic inflammation reaction. The VC implanted with PTFE presented eosinophilic infiltration (Kruskal-Wallis, P<.05). CONCLUSION: Both GBP and LGBP can be used as implants for VC medialization because they are biocompatible, have easy surgical manoeuvrability, do not suffer absorption, migration or extrusion and produce inflammation reactions similar to those of PTFE.

Effects of middle ear packing with collagen polyvinylpyrrolidone and hyaluronic acid in guinea pigs.

OBJECTIVE: The aim of this study was to evaluate otoscopic and microscopic changes produced on the healthy mucosa of the middle ear (ME) and tympanic membrane (TM) of guinea pigs after packing with a collagen polyvinylpyrrolidone (CPVP) sponge soaked in hyaluronic acid (HA). MATERIAL AND METHODS: In 24 guinea pigs, myringotomy on the right side was created and the ME was packed as follows: Group I (n = 6): Absorbable gelatin sponge (AGS) soaked in saline solution; Group II (n = 6): AGS sponge soaked in HA, Group III (n = 6): CPVP sponge soaked in saline solution, Group IV (n = 6): CPVP sponge soaked in HA. Four weeks after miringotomy, the ME and TM integrity and residual packing material were evaluated otoscopically. Histologically, we evaluated inflammatory changes on the ME mucosa. RESULTS: All animals in Groups I and II showed residual packing material (p < .001 ANOVA, TUKEY). Histologically, more inflammation was observed in Groups I, II, and III than in Group IV (p < .001 ANOVA, TUKEY). Group IV showed greater fibroblastic reaction (p < .02, ANOVA, TUKEY) versus other groups. CONCLUSION: The CPVP sponge soaked in HA used as ME packing material is biocompatible and nontoxic, because it produces minimal inflammatory changes on the healthy mucosa of the ME and TM of guinea pigs. However, more research with injured mucosa is needed to validate its usefulness in otosurgery.

[Effects of propofol pretreatment on endothelin in oleic acid-induced acute lung injury]. / Efectos del pretratamiento con propofol sobre la endotelina en daño pulmonar agudo inducido por ácido oleico.

INTRODUCTION: Acute lung injury (ALI) is a pathological condition characterized by injury in the alveolar-capillary membrane that triggers local and systemic inflammation. Endothelin (ET) is a protein that regulates immune response and constricts blood vessels; when it is over-expressed, it may contribute to high blood pressure and lung injury. This work tries to determine if propofol may decrease hemodynamic, gasometric, microscopic, ET-1 plasmatic concentration, and immuno-histochemical alterations in an experimental model of oleic acid-induced acute lung injury. MATERIALS AND METHODS. Animals were classified into three groups (n = 6): group I was the control group; in group II, there was oleic acid-induced ALI with no treatment, and group III with propofol pre-treatment and oleic acid-induced ALI. RESULTS: All animals survived until the end of the study, and 100% of group II and group III developed ALI, with hemodynamic, gasometric and gravimetric alterations. However, group III showed less inflammatory infiltration and lower ET-1 expression in lung tissue. CONCLUSIONS: Pretreatment with propofol in a canine model of OA-induced ALI indicates that the drug has anti-inflammatory action, with a potential therapeutic role against progression of anti-inflammation and lung damage.

[Experimental model of canine oleic acid-induced acute lung injury: establishment of a working model]. / Modelo experimental canino de daño pulmonar agudo producido con ácido oleico: estableciendo un modelo de trabajo.

INTRODUCTION: There are several experimental model of acute lung injury induced by oleic acid (OA); however, there are few studies that show how this injury develops. OBJECTIVE: This study seeks to detail the x-ray, hemodynamic, gasometrical, gravimetrical, macroscopic and microscopic alterations developed in an experimental model of canine OA-induced acute lung injury (ALI). MATERIAL AND METHODS: Twelve dogs were divided in 2 study groups: Group I (n=6): Control group without ALI. Group II (n=6); OA-induced ALI. All dogs were submitted to X-ray, hemodynamic and gasometric evaluation before ALI induction, and later every 15 minutes during 150 minutes. At the end of the study, the animals were euthanatized and were evaluated the changes gravimetric, macroscopic and microscopic in injured lungs. RESULTS: All the animals survived through the study. In group II, 100% of the animals developed x-ray (p < 0.003 Wilcoxon), hemodynamic, gasometrical and gravimetric (p < 0.5 ANOVA, Tukey), macroscopically and microscopically (p < 0.001 Wilcoxon) ALI. CONCLUSIONS: The OA-induced ALI is a model in which dogs develop X-ray, hemodynamic, gasometrical, gravimetrical, macroscopically and microscopically injuries of the exudative phase that lung with ALI injury presents.

Wound healing modulators in a tracheoplasty canine model.

Postsurgical tracheal stenosis results from fibrosis formation due to ischemia. There are healing modulators, hyaluronic acid (HA) and collagen polyvinylpyrrolidone (CPVP), which reduce collagen fibers formation. Thus we can hypothesize that the topical application of one of these modulators can diminish postsurgical tracheal scarring and stenosis. The aim of this work was to evaluate the macroscopic, microscopic, and biochemical changes of tracheal healing after the application of HA or CPVP in a canine tracheoplasty model. The study design was prospective experimental investigation in a canine model. Eighteen mongrel dogs underwent three cervical tracheal rings resection and end-to-end anastomosis. They were randomized into three groups according to treatment: group I (control group) (n = 6), topical application of saline solution on tracheal anastomosis; group II (n = 6), topical application of 15 microg HA on tracheal anastomosis; and group III (n = 6), topical application of 2.5 mg CPVP on tracheal anastomosis. They were evaluated clinical, radiological and tracheoscopically during 4 weeks. They were euthanized at the end of the study time. Macroscopic, microscopic, and biochemical changes of tracheal anastomosis healing were analyzed. Collagen formation was quantified by the Woessner method. All the animals survived the surgical procedure and study period. Macroscopic, radiologic, and endoscopic studies showed that animals in group I developed tracheal stenosis, inflammation, and firm fibrous tissue formation, and histological studies also showed severe inflammatory reaction and fibrosis formation. Groups II (HA) and III (CPVP) showed well-organized thin collagen fibers with minimal inflammatory response. Biochemical evaluation revealed a higher collagen concentration in group I animals (analysis of variance [ANOVA] p < .05 and Tukey p < .01). Thus, hyaluronic acid or collagen polyvinylpyrrolidone administered after tracheal anastomosis diminished the degree of stenosis and inflammatory reaction. Both modulators improved tracheal healing.