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Pre-ulcerative villous contraction and microvascular occlusion induced by indomethacin in the rat jejunum: a detailed
A Anthony1, A P Dhillon, C Thrasivoulou
1Inflammatory Bowel Disease Study Group, University Department of Histopathology, Royal Free Hospital School of Medicine, London, UK.
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.
Aim:
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.
Conclusion:
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.