Pre-ulcerative villous contraction and microvascular occlusion induced by indomethacin in the rat jejunum: a detailed morphological study.
BACKGROUND
In indomethacin-induced jejunal ulceration in the rat, villi undergo both early microvascular injury and shortening that may involve activation of villous smooth muscle.


OBJECTIVE
This study sought to substantiate light microscopic observations using three-dimensional imaging of early villous architectural changes in response to indomethacin.


METHODS
At both 2 and 6 h after oral indomethacin 15 mg/kg or vehicle to groups of rats, the vasculature of the small intestine was visualised by both carbon-ink perfusion/confocal microscopy and injection casting. The mucosa was also examined for lesions by dissection microscopy and scanning electron microscopy.


RESULTS
In indomethacin-dosed rats examined by scanning electron microscopy and histology, the mucosa at 2 h showed villous shortening and wrinkling of the surface epithelium without epithelial loss; at 6 h, the mucosa was flattened, often with epithelial loss to expose a 'contracted' villous core. Examination of the 'vasculature in carbon-injected tissues indicated significant reductions of both mucosal height and inter-capillary distance at both 2 and 6 h post-indomethacin. Scanning electron microscopy of injection casts at 2 and 6 h indicated similar changes. These changes were not seen in control tissues.


CONCLUSIONS
Histology, confocal microscopy and scanning electron microscopy support the proposal that villous shortening with disruption of surface capillary architecture are early changes in the ulcerative enteropathy induced by nonsteroidal anti-inflammatory drugs.
Anthony
A
A
Inflammatory Bowel Disease Study Group, University Department of Histopathology, Royal Free Hospital School of Medicine, London, UK.
Dhillon
A P
AP
Thrasivoulou
C
C
Pounder
R E
RE
Wakefield
A J
AJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D007213:Indomethacin / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000648:ultrastructure; D007579:Jejunal Diseases / Q000139:chemically induced* / Q000473:pathology; D007583:Jejunum / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D014456:Ulcer / Q000139:chemically induced* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin