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Eur J Pediatr Surg 2020; 30(06): 517-523
DOI: 10.1055/s-0039-3400285
Original Article

Intramural Injection of Botulinum Toxin A in Surgical Treatment of a Long Gap Esophageal Atresia—Rat Model

Ashton Hideki Pike
1   Department of Surgery, University of Vermont Larner College of Medicine, Burlington, Vermont, United States
,
Peter Zvara
2   Department of Clinical Research, University of Southern Denmark, Odense, Syddanmark, Denmark
,
Marijana Rincic Antulov
3   Department of Surgery, Sygehus Sønderjylland, Aabenraa, Denmark
,
Henrik Daa Schrøder
4   Department of Pathology, Odense University Hospital, Odense, Denmark
,
Eva Kildall Hejboel
4   Department of Pathology, Odense University Hospital, Odense, Denmark
,
Lars Rasmussen
5   Department of Surgery, Odense University Hospital, Odense, Denmark
,
Niels Qvist
5   Department of Surgery, Odense University Hospital, Odense, Denmark
,
Mark Bremholm Ellebæk
5   Department of Surgery, Odense University Hospital, Odense, Denmark
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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.

Keywords

rats - esophageal atresia - botulinum toxin A - long gap esophageal atresia - anastomosis


Publication History

Received: 07 June 2019

Accepted: 04 October 2019

Article published online:
13 December 2019

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