J Chest Surg.  2021 Jun;54(3):191-199. 10.5090/jcs.20.146.

Experimental Tracheal Replacement: Angiogenesis and Null Apoptosis Promote Stenosis

• Santibáñez-Salgado JA
• Sotres-Vega A
• Gaxiola-Gaxiola MO
• Villalba-Caloca J
• Lozoya KB
• Zúñiga-Ramos JA

• KMID: 2516512
• DOI: http://doi.org/10.5090/jcs.20.146

Abstract

Background
Tracheal replacement is a challenge for thoracic surgeons due to stenosis in the trachea-prosthesis anastomosis. We propose that stenosis occurs due to fibrosis as a result of an abnormal healing process, characterized by an increased expression of wound healing growth factors (vascular endothelial growth factor [VEGF], survivin, and CD31), which promote angiogenesis and decrease apoptosis. We analyzed the immunoreactivity of VEGF, survivin, CD31, and caspase-3 in the development of fibrotic stenosis in prosthetic tracheal replacement.
Methods
Fourteen dogs were operated on: group I (n=7) received a 6-ring cervical tracheal segment autograft, while in group II (n=7), a 6-ring segment of the cervical trachea was resected and tracheal continuity was restored with a Dacron prosthesis. The follow-up was 3 months. Immunoreactivity studies for VEGF, survivin, CD31, and caspase-3 were performed. A statistical analysis was done using the Wilcoxon signed rank test.
Results
Four animals in group I were euthanized on the 10th postoperative day due to autograft necrosis. Three animals completed the study without anastomotic stenosis. Moderate expression of VEGF (p=0.038), survivin (p=0.038), and CD31 (p=0.038) was found. All group II animals developed stenosis in the trachea-prosthesis anastomotic sites. Microscopy showed abundant collagen and neovascularization vessels. Statistically significant immunoreactive expression of VEGF (p=0.015), survivin (p=0.017), and CD31 (p=0.011) was observed. No expression of caspase-3 was found.
Conclusion
We found a strong correlation between fibrosis in trachea-prosthesis anastomoses and excessive angiogenesis, moderate to intense VEGF, CD31, and survivin expression, and null apoptotic activity. These factors led to uncontrolled collagen production.

Keyword

Trachea; Prosthesis; Angiogenesis; Apoptosis; Fibrosis