Mechanical properties of obstructed colon in a Hirschsprung's model

Hirschsprung's disease, induced by aganglionosis of the distal intestinal tract, results in significant morbidity in affected children. This study uses a murine model of congenital aganglionosis in the distal colon to determine the effects of this type of obstruction on the proximal colon. In lethal spotted mice (Ls/Ls) there is a greater increase in the thickness of circular muscle (in the obstructed colon immediately proximal to the aganglionic region) than longitudinal muscle compared with controls. The active forces generated in vitro, as determined by length-tension curves of the circular muscle, are larger than in control littermates, and isolated muscle cells from the area proximal to the obstruction are larger and shorten to a significantly greater degree in response to acetylcholine. These data are consistent with increased muscle mass subsequent to hypertrophy, although simultaneously occurring hyperplasia cannot be excluded. However, the increased forces that developed are not entirely explained by increased muscle mass. When forces are normalized per cross-sectional unit of circular muscle present in the obstructed rings, stress is considerably higher in the rings proximal to the obstruction than in matched rings from obstruction-free littermates. Pressure-diameter relationships calculated from in vitro data show that the Ls/Ls colon is capable of exerting higher intraluminal pressures than the control colon. The increases in circular muscle thickness, forces, and stress are similar to those observed in other models of obstruction. The increased pressure-diameter relationships observed in the colon are unlike an experimental model of obstruction in the ureter and may reflect longstanding obstruction or a difference in response of colonic muscle to obstruction. It is possible that these mechanical changes may affect the course of Hirschsprung's disease.