Electrical stimulation of the vagus nerve restores motility in an animal model of achalasia

Abstract

Esophageal peristalsis generally does not return to normal after surgical treatment of achalasia. Direct electrical stimulation of the vagus nerve is known to stimulate antegrade peristalsis in the normal esophagus; however, it is not known whether electrical stimulation will induce return of peristalsis once an achalasia-like disorder has been established. The objective of this study was to perform quantitive and qualitative measurements of motility during electrical stimulation of the vagal nerve in an animal model of achalasia. An already established and verified animal achalasia model using adult North American opossums (Didelphis virginiana) was used. Fifteen opossums were divided into three groups. Sham surgery was performed on three animals (group 1). In group 2 (n=6) a loose Gore-Tex band (110% of the esophageal circumference) was placed around the gastroesophageal junction to prevent relaxation of the lower esophageal sphincter during swallowing. In group 3 (n=6) a relatively tighter band (90% of the esophageal circumference) was used to further elevate the lower esophageal sphincter pressure. At 6 weeks, after manometric and radiolologic confirmation of achalasia, electrical stimulation of the esophagus was performed before and after removal of the band using a graduated square-wave electrical stimulus. Changes in esophageal neural plexi were assessed histologically. Pre- and postoperative manometric data were compared using standard statistical techniques. No difference was observed in esophageal characteristics and motility after sham surgery in group 1. Animals in group 2 demonstrated a vigorous variety of achalasia (high-amplitude, simultaneous, repetitive contractions), moderate esophageal dilatation, and degeneration of 40% to 60% of intramuscular nerve plexi. Animals in group 3 developed amotile achalasia with typical low-amplitude simultaneous (mirror image) contractions, severely dilated ("bird beak") esophagus, and degeneration of 50% to 65% of nerve plexi. Vagal stimulation in group 2 demonstrated a significant increase in the amplitude of contractions (P<0.001) and return of peristaltic activity in 49% of swallows before band removal. After band removal, all of the contractions were peristaltic. In group 3 vagal stimulation before and after removal of the band demonstrated a significant increase in amplitude of contractions (P<0.0001) but no return of propagative peristalsis before band removal, however, 44% of contractions were progressive in the smooth portion of the esophagus after removal of the band. Electrical stimulation of the vagus nerve improved the force of esophageal contractions irrespective of the severity of the disease; however, peristaltic activity completely returned to normal only in the vigorous (early) variety of achalasia. Removal of the functional esophageal outlet obstruction, as with a surgical myotomy, may be necessary to obtain significant peristalsis with vagal pacing in severe achalasia.

The Pathogenesis and Management of Achalasia: Current Status and Future Directions

“…In fact, extrinsic innervation abnormality is a rare finding in achalasia patients and is most likely not the primary mechanism of the disease. 29 – 31 …”

Achalasia: physiology and etiopathogenesis

“…Esophageal body aperistalsis characteristic of achalasia occurs over time in most patients with either primary or pseudoachalasia. It has further been demonstrated that esophageal body contractions are abnormal in animal models where the LES is surgically constricted 77 as well as in some post surgical patients in whom resting LES pressures are abnormally high 20 . This suggests that together with loss of enteric neurons in the body of the esophagus, dysfunction at the level of the LES may also contribute to disordered peristalsis in the esophageal body.…”

Idiopathic (primary) achalasia

“…Several studies on humans and animals [ 20 , 21 ] have suggested that extrinsic causes such as lesions located in the central nervous system (CNS) may produce manometric findings of achalasia. Abnormalities of the vagal nerve fibers outside the CNS has also been associated with achalasia; however, extrinsic innervation abnormalities are rare findings in achalasia patients [ 22 - 24 ] and are thus probably not the primary mechanism of the disease.…”