Interstitial Cells of Cajal in Dysmotility in Intestinal Ischemia and Reperfusion Injury in Rats

Abstract

Intestinal ischemia and reperfusion (I/R) injury is an obligatory occurrence in small bowel transplantation. I/R may impair the normal gastrointestinal motility. Interstitial cells of Cajal (ICC) are known as pacemaker cells in the gastrointestinal tract. The aim of this study was to assess the role of ICC in the gastrointestinal motility in a rat model of I/R injury. Wistar rats were subjected to 30- or 80-min intestinal ischemia by occluding the mesenteric vessels followed by reperfusion. Small intestinal segments were resected at 12 h or 4 days. The spontaneous mechanical activity was evaluated by organ bath technique. Immunopositivity of c-Kit and PGP9.5 at the level of the myenteric plexus was evaluated as markers of ICC and enteric nerves, respectively. In the bowel segment with 80-min ischemia followed by 12-h reperfusion, muscles showed a 25% reduction (P < 0.05) in the frequency of contractions compared to that with 30-min ischemia followed by 12-h reperfusion, whereas amplitude of contractions was not significantly different. This change was associated with a 70% decrease (P < 0.01) of c-Kit immunopositivity. These changes of intestinal motility pattern and distribution of c-Kit-positive cells were both recovered from 80-min ischemia followed by 4 days reperfusion. In contrast, the immunopositivity of PGP9.5 was not affected in any I/R injury group. Transient functional changes in ICC were induced by prolonged I/R injury but they recovered after 4 days, suggesting a central role of ICC in both disrupting and restoring the normal gastrointestinal motility in I/R injury.