Recombinant vascular endothelial growth factor165 gene therapy improves anastomotic healing in an animal model of ischemic esophagogastrostomy

• Published in: Diseases of the esophagus Vol. 25; no. 5; pp. 456 - 464
• Main Authors: Enestvedt, C. K., Hosack, L., Hoppo, T., Perry, K. A., O'Rourke, R. W., Winn, S. R., Hunter, J. G., Jobe, B. A.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01-07-2012
• Subjects: anastomosis; Anastomosis, Surgical - methods; Anastomotic Leak - prevention & control; Animals; Didelphis; Disease Models, Animal; Esophagectomy - methods; esophagus; Esophagus - blood supply; Esophagus - surgery; Gastrectomy - methods; Genetic Therapy - methods; healing; Humans; ischemia; Ischemia - prevention & control; Neovascularization, Physiologic - genetics; Real-Time Polymerase Chain Reaction; RNA, Messenger - analysis; Stomach - blood supply; Stomach - surgery; Transfection; vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Wound Healing - genetics
• ISSN: 1120-8694; 1442-2050
• DOI: 10.1111/j.1442-2050.2011.01247.x

SUMMARY
Proper anastomotic healing is dependent upon many factors including adequate blood flow to healing tissue. The aim of this study was to investigate the impact of vascular endothelial growth factor (VEGF165) transfection on anastomotic healing in an ischemic gastrointestinal anastomosis model. Utilizing an established opossum model of esophagogastrectomy followed by esophageal–gastric anastomosis, the gastric fundus was transfected with recombinant human vascular endothelial growth factor via direct injection of a plasmid‐based nonviral delivery system. Twenty‐nine animals were divided into three groups: two concentrations of VEGF and a control group. Outcomes included VEGF mRNA transcript levels, neovascularization, tissue blood flow, and anastomotic bursting pressure. To determine whether local injection resulted in a systemic effect, distant tissues were evaluated for VEGF transcript levels. Successful gene transfection was demonstrated by quantitative polymerase chain reaction analysis of anastomotic tissue, with significantly higher VEGF mRNA expression in treated animals compared to controls. At the gastric side of the anastomosis, there was significantly increased neovascularization, blood flow, and bursting pressure in experimental animals compared to controls. There were no differences in outcome measures between low‐ and high‐dose VEGF groups; however, the high‐dose group demonstrated increased VEGF mRNA expression across the anastomosis. VEGF production was not increased at distant sites in treated animals. In this animal model, VEGF gene therapy increased VEGF transcription at a healing gastrointestinal anastomosis without systemic VEGF upregulation. This treatment led to improved healing and strength of the acutely ischemic anastomosis. These findings suggest that VEGF gene therapy has the potential to reduce anastomotic morbidity and improve surgical outcomes in a wide array of patients.