Intrasphinktere Botulinumtoxin A Injektion versus Myotomie nach Heller — Manometrischer und pH-metrischer Vergleich zweier Techniken zur Induktion von gastro-ösophagealem Reflux im Schweinemodell

Abstract

Aim: To establish a model in piglets as effective in inducing gastroesophageal reflux as previously shown for cardiomyotomy but less invasive and easier to apply in any kind of basic research on reflux disease. Intrasphincteric injection of botulinumtoxin A (Botox®) in the lower esophageal sphincter (LES) by endoscopy could be such a model. Background: Botulinumtoxin inhibits the release of acetylcholine from nerve terminals and causes paralysis of smooth muscle. No comparison of Heller ‘s myotomy and botulinumtoxin as an experimental reflux model has yet been presented. Material and Methods: We compared both procedures, the Heller myotomy and the injection of botulinumtoxin into the LES. Intrasphincteric pressure was measured by manometry based vector volume and reflux episodes were measured by long-term pH-monitoring previously established by our group. All studies were performed in male piglets, between 40 – 50 kg of weight. After an overnight fast presedation was administered. Thereafter, intravenous ketamine (l00 mg/kg BW), midazolam (30 mg/kg BW) and Ringer solution (500 ml/h) were administered and a cuffed endotracheal tube was placed. Animals were randomly allocated to receive either cardiomyotomy (n = 5) or Botox injection (n = 5). Studies were performed before, 2–3 days after as well as 21 days after the respective procedure. The manometry was performed by rapid pull-through technique in apnoe after hyperventilation. 24 h pH-monitoring was performed using standard 2 channel antimon probes placed endoscopically. Cardiomyotomy was performed through a left subcostal incision in the typical manner. Botulinumtoxin A was injected into all four quadrants at two different levels of the high pressure zone. Results: Mean pressure (9,5 vs. 6,8 mmHg) and vector volume (1977 vs. 823 mmHg x cm2) were significantly reduced by myotomy (p < 0,05). After endoscopic injection of botulinumtoxin, mean pressure (8,86 vs. 6,7 mmHg) and vector volume (1024 vs. 302 mmHg x cm2) were significant reduced as well (p <0,05). With endoscopic intrasphincteric injection of botulinumtoxin A mean LES pressure was significantly reduced by about 70% from baseline. Significantly, pathologic gastroesophageal reflux was confirmed in both groups.Conclusion:The ‘minimally invasive Botox model’ as a technique to induce reflux is valid and reproducible.