Abstracts
1997 Digestive Disease Week

Histology and function of the internal anal sphincter after intrasphincteric injection of botulinum toxin.

JC Langer, E Birnbaum, R Schmidt. Washington University, St. Louis, MO.

Background: Children with Hirschsprung's disease may have persistent obstructive symptoms due to hypertonicity of the internal anal sphincter (IAS), even after definitive surgery. Anal myectomy is not universally effective and may result in permanent sphincter injury. Botulinum toxin (BTX) injection has been used to selectively weaken a variety of muscles, and could theoretically represent a less invasive option for children with this difficult problem. We therefore evaluated the efficacy and safety of BTX in an immature porcine model.

Methods: Six-week old piglets underwent 4-quadrant intrasphincteric injection of BTX (total dose 15 units) or saline. Under ketamine sedation, IAS resting pressure (mm Hg) was measured using a water-perfused system before injection and 4 weeks later. Animals were sacrificed 4 weeks after injection. Histological evidence of neuromuscular changes or inflammation in the IAS was documented using a scale from 0-3. All analysis was done blindly.

Results: Results are shown below (*p<0.05).

                           Saline (n=5)    BTX (n=5)
 Pre/post IAS pressure*    0.49 ± .1       1.90 ± .7
 Neuronal size             1.80 ± .4       1.90 ± .4
 Neuronal number           2.00 ± .9       2.20 ± .4
 Nerve trunk size          1.80 ± .2       2.00 ± .3
 Nerve trunk number        1.70 ± .2       2.00 ± .5
 Inflammation              1.80 ± .4       1.90 ± .4
 Muscle atrophy            0               0

Conclusions: Internal anal sphincter pressure increased in control animals, likely due to growth over the 4 week period. Conversely, BTX caused a significant decrease in IAS pressure, without histological evidence of sphincter injury. These data justify a clinical trial using BTX for persistent obstructive symptoms following surgery for Hirschsprung's disease.