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

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.

Endoscopic Injections of Botulinum Toxin Type A in the Piglet Esophagus Is Safe and Feasible but Did Not Result in any Significant Structural Changes 3 Days after Injection

“…8 In the rat model, the elongation was higher after a waiting period of 24 hours compared with 6 hours confirming the time-related effect of BTX-A. 9 All studies were performed with the BTX-A injections on an in vivo exposed esophagus. As the peak in effect of BXT-A occurs between 1 and 3 weeks after administration, 10 11 preoperative administration seems more attractive.…”

“…6 7 8 9 This effect has been shown to be time dependent. 8 9 We were not able to recreate these results in this study, as we found no statistically significant difference between BTX-A and placebo when placing the injections endoscopically and with a 3-day waiting period. However, we were able to show a nonsignificant lower maximum load for the BTX-A group which is in line with the expected physiological effect of BTX-A.…”

“…BTX-A injections into the wall of esophagus in piglets and rats have demonstrated a significantly increased esophageal elongation under tension. [6][7][8][9] In addition, it showed a reduction in the incidence of stricture formation and enhanced anastomotic healing of the esophageal-esophageal anastomosis 9 which might be an additional advantage of the treatment with BTX-A. We have previously shown that the optimal dose is 2 units/kg body weight.…”

The Effect of Botulinum Toxin Type A Injections on Stricture Formation, Leakage Rates, Esophageal Elongation, and Anastomotic Healing Following Primary Anastomosis in a Long- and Short-Gap Esophageal Atresia Model – A Protocol for a Randomized, Controlled, Blinded Trial in Pigs

“…In addition, BTX-A inhibits the release of other neurotransmitters important for tonic muscular status, including adenosine triphosphate. Previous studies from our research group have shown that injections of BTX-A into the esophageal musculature in pigs and rats lead to a significant increase in esophageal elongation [ 18 19 ]. In addition, early evidence suggests a reduced stricture formation following esophageal anastomosis [ 19 ].…”

“…Previous studies from our research group have shown that injections of BTX-A into the esophageal musculature in pigs and rats lead to a significant increase in esophageal elongation [ 18 19 ]. In addition, early evidence suggests a reduced stricture formation following esophageal anastomosis [ 19 ]. We have also shown that administration of BTX-A via endoscopic techniques is feasible, and that the effect of BTX-A on esophageal elongation is dosage- and time-dependent [ 20 21 ].…”