FOCAL REDUCTION OF VILLOUS BLOOD-FLOW IN EARLY INDOMETHACIN ENTEROPATHY - A DYNAMIC VASCULAR STUDY IN THE RAT

Background-Oral indomethacin causes villous shortening, microvascular damage, and distortion, which might induce mucosal ischaemia and necro sis. Aims-In order to determine the early events in indomethacin induc ed jejunal injury we examined the temporal relations between morpholog ical damage and changes in villous blood flow following indomethacin. Methods-In anaesthetised rats, mid jejunal villi were exteriorised in a chamber and observed by fluorescence microscopy. Blood flow in surfa ce capillaries was calculated from velocities and diameters. Indometha cin was applied by both luminal and intravenous routes for 90 minutes, after which the animal was perfusion fixed and the villi were process ed for histological examination. Control animals received intravenous or luminal bicarbonate (1.25%). Results-Blood flow slowed in individua l villi at 20 minutes, and progressed to complete stasis (in another g roup) by 45 minutes. Histological examination at 20 minutes revealed m icrovascular distortion, but no shortening: crypt depth:villous ratios were 0.356 (0.02) in test and 0.386 (0.01) in surrounding villi (p>0. 5). At stasis, the villi under study showed epithelial clumping and we re shortened: crypt depth:villous height ratios were 0.92 (0.2) in tes t and 0.42 (0.06) in surrounding villi (p<0.02). Vehicle alone had no effect on either blood flow or histology. Conclusions-Focal slowing of villous blood flow and microvascular distortion precede villus shorte ning and epithelial disruption, and indicate that damage to surface mi crovasculature is an early event in indomethacin induced mucosal injur y in this model.