Damaging effects of ischemia/reperfusion on intestinal muscle

Abstract

Periods of ischemia followed by restoration of blood flow cause ischemia/reperfusion (I/R) injury. In the intestine, I/R damage to the mucosa and neurons is prominent. Functionally, abnormalities occur in motility, most conspicuously a slowing of transit, possibly as a consequence of damage to neurons and/or muscle. Here, we describe degenerative and regenerative changes that have not been previously reported in intestinal muscle. The mouse small intestine was made ischemic for 1 h, followed by re-perfusion for 1 h to 7 days. The tissues were examined histologically, after hematoxylin/eosin and Masson’s trichrome staining, and by myeloperoxidase histochemistry to detect inflammatory reactions to I/R. Histological analysis revealed changes in the mucosa, muscle, and neurons. The mucosa was severely but transiently damaged. The mucosal surface was sloughed off at 1–3 h, but re-epithelialization occurred by 12 h, and the epithelium appeared healthy by 1–2 days. Longitudinal muscle degeneration was followed by regeneration, but little effect on the circular muscle was noted. The first signs of muscle change were apparent at 3–12 h, and by 1 and 2 days, extensive degeneration within the muscle was observed, which included clear cytoplasm, pyknotic nuclei, and apoptotic bodies. The muscle recovered quickly and appeared normal at 7 days. Histological evidence of neuronal damage was apparent at 1–7 days. Neutrophils were not present in the muscle layers and were infrequent in the mucosa. However, they were often seen in the longitudinal muscle at 1–3 days and were also present in the circular muscle. Neutrophil numbers increased in the mucosa in both I/R and sham-operated animals and remained elevated from 1 h to 7 days. We conclude that I/R causes severe longitudinal muscle damage, which might contribute to the long-term motility deficits observed after I/R injury to the intestine.