Ashton Hideki Pike1, Peter Zvara2, Marijana Rincic Antulov3, Henrik Daa Schrøder4, Eva Kildall Hejboel4, Lars Rasmussen5, Niels Qvist5, Mark Bremholm Ellebæk5. 1. Department of Surgery, University of Vermont Larner College of Medicine, Burlington, Vermont, United States. 2. Department of Clinical Research, University of Southern Denmark, Odense, Syddanmark, Denmark. 3. Department of Surgery, Sygehus Sønderjylland, Aabenraa, Denmark. 4. Department of Pathology, Odense University Hospital, Odense, Denmark. 5. Department of Surgery, Odense University Hospital, Odense, Denmark.
Abstract
INTRODUCTION: Anastomosis with minimal tension is desirable in long-gap esophageal atresia. Prior studies in piglets showed that intraesophageal injection of botulinum toxin type A (BTX-A) results in significant esophageal elongation. Our aim was to determine the BTX-A dose, number of injections, and time necessary to elicit maximal response. MATERIALS AND METHODS: Adult male Wistar rats (n = 48) were randomly assorted into five groups. Four treatment groups received 2 or 4 U/kg of BTX-A, delivered using two or four injections, and a control group received 0.9% NaCl. Esophagus was removed 6 or 24-hours postinjection and tested ex vivo using a stretch tension device. Subsequently, an optimal dose and time following injection was used to study the effects of BTX-A on anastomotic healing in vivo. Rats (n = 12) received an intraesophageal injection of BTX-A or 0.9% NaCl, followed by resection of 0.5 cm of esophagus and end-to-end anastomosis. Rats were observed for 9 days, and esophagus was removed for gross and histological evaluation. RESULTS: The largest effect on elongation was recorded in the BTX-A (2 U/kg) 24 hour, four injection group. In the anastomosis study, stricture formation was observed in all animals in the control group. Absence of esophageal stricture was found in three out of four animals in the treatment group macroscopically and histologically. CONCLUSION: We found that BTX-A exerts a positive effect on stretch characteristics of esophageal tissue in rats at 2 U/kg via four-injection delivery and 24-hour waiting period. This study suggests that BTX-A might improve anastomotic healing. Thieme. All rights reserved.
INTRODUCTION: Anastomosis with minimal tension is desirable in long-gap esophageal atresia. Prior studies in piglets showed that intraesophageal injection of botulinum toxin type A (BTX-A) results in significant esophageal elongation. Our aim was to determine the BTX-A dose, number of injections, and time necessary to elicit maximal response. MATERIALS AND METHODS: Adult male Wistar rats (n = 48) were randomly assorted into five groups. Four treatment groups received 2 or 4 U/kg of BTX-A, delivered using two or four injections, and a control group received 0.9% NaCl. Esophagus was removed 6 or 24-hours postinjection and tested ex vivo using a stretch tension device. Subsequently, an optimal dose and time following injection was used to study the effects of BTX-A on anastomotic healing in vivo. Rats (n = 12) received an intraesophageal injection of BTX-A or 0.9% NaCl, followed by resection of 0.5 cm of esophagus and end-to-end anastomosis. Rats were observed for 9 days, and esophagus was removed for gross and histological evaluation. RESULTS: The largest effect on elongation was recorded in the BTX-A (2 U/kg) 24 hour, four injection group. In the anastomosis study, stricture formation was observed in all animals in the control group. Absence of esophageal stricture was found in three out of four animals in the treatment group macroscopically and histologically. CONCLUSION: We found that BTX-A exerts a positive effect on stretch characteristics of esophageal tissue in rats at 2 U/kg via four-injection delivery and 24-hour waiting period. This study suggests that BTX-A might improve anastomotic healing. Thieme. All rights reserved.
Authors: Emma Svensson; Peter Zvara; Niels Qvist; Lars Hagander; Sören Möller; Lars Rasmussen; Henrik Daa Schrøder; Eva Kildall Hejbøl; Niels Bjørn; Súsanna Petersen; Kristine Cederstrøm Larsen; Jan Krhut; Oliver J Muensterer; Mark Bremholm Ellebæk Journal: Int J Surg Protoc Date: 2021-08-11