[Microcirculation studies on rat small intestine villi in vivo].
ABSTRACT A method of observing and studying the microcirculation in the jejunal villus of the living rat is described. It permits measurement of the velocity of plasma gaps and of the diameters of the various vessels, and is based on transillumination of the exposed mucosa. The motility of the gut is overcome by allowing the intestine to adhere to the water-immersion lens. The problems of mucous secretion are resolved by administration of N-acetyl-L-cystein. A direct arteriovenous connection between arterioles and the venous system of the villus is postulated. Plasma gap velocity is 1.78 +/- 0.62 mm/sec in the arterioles and 0.42 +/- 0.08 mm/sec in the capillaries. The measured diameter of the of the erythrocyte column in the vessels is: central artery: 9.14 +/- 1.89 micron; "arcade" arteriole part I, II and III respectively: 5.88 +/- 1.05 micron, 6.69 +/- 1.04 micron, 8.86 +/- 1.63 micron; venule: 13.58 +/- 2.67 micron; capillaries: 4.56 +/- 0.57 micron. The method also allows puncture of the villus vessels.
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ABSTRACT: Oral indomethacin causes villous shortening, microvascular damage, and distortion, which might induce mucosal ischaemia and necrosis. In order to determine the early events in indomethacin induced jejunal injury we examined the temporal relations between morphological damage and changes in villous blood flow following indomethacin. In anaesthetised rats, mid jejunal villi were exteriorised in a chamber and observed by fluorescence microscopy. Blood flow in surface capillaries was calculated from velocities and diameters. Indomethacin was applied by both luminal and intravenous routes for 90 minutes, after which the animal was perfusion fixed and the villi were processed for histological examination. Control animals received intravenous or luminal bicarbonate (1.25%). Blood flow slowed in individual villi at 20 minutes, and progressed to complete stasis (in another group) by 45 minutes. Histological examination at 20 minutes revealed microvascular distortion, but no villous shortening; crypt depth:villous height ratios were 0.356 (0.02) in test and 0.386 (0.01) in surrounding villi (p > 0.05). At stasis, the villi under study showed epithelial clumping and were shortened: crypt depth:villous height ratios were 0.92 (0.2) in test and 0.42 (0.06) in surrounding villi (p < 0.02). Vehicle alone had no effect on either blood flow or histology. Focal slowing of villous blood flow and microvascular distortion precede villus shortening and epithelial disruption, and indicate that damage to surface microvasculature is an early event in indomethacin induced mucosal injury in this model.Gut 03/1998; 42(3):366-73. DOI:10.1136/gut.42.3.366 · 13.32 Impact Factor
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ABSTRACT: Indomethacin has been shown to damage the villous microvasculature concomitant with alterations in villous blood flow in the rat. To test the hypothesis that alterations in blood flow result from ultrastructural damage to microvasculature endothelium. In anaesthetized rats, jejunal villi were exteriorized in a chamber and blood flow in surface capillaries visualized by fluorescence microscopy. Villi were exposed both luminally and systemically to indomethacin (100 microg/mL) for 10 min or until blood slowing or stasis had occurred in superficial capillaries (n=3 per group). Control animals received both a luminal and intravenous vehicle for 45 min (n=3). The small intestines were vascular perfusion-fixed with 1.5% glutaraldehyde and studied by transmission electron microscopy. All controls appeared to be ultrastructurally normal. A 10 min exposure to indomethacin had no effect upon the epithelium but resulted in mild endothelial vacuolization and the development of small finger-like projections into the lumen of villus surface microvasculature. At the point of blood slowing, villus tip epithelium was again normal but the endothelial vacuolization and finger-like projections became more obvious. The endothelial projections and vacuolization became severe at the point of blood stasis; this also coincided with epithelial degeneration. This study shows that villus surface microvasculature is the earliest site of morphological damage after indomethacin exposure.Alimentary Pharmacology & Therapeutics 05/2000; 14(4):489-96. DOI:10.1046/j.1365-2036.2000.00702.x · 5.48 Impact Factor
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ABSTRACT: In the rat, indomethacin causes jejunal villous shortening, microvascular distortion, and blood stasis prior to ulceration. The beta3-adrenoceptor agonist CL316,243 (CL) prevents both the early histological changes and ulceration. To test the hypothesis that the beta3-adrenoceptor agonist CL316,243 exerts its protective effect by prevention and/or reversal of blood flow changes in the rat jejunum exposed to indomethacin. In anaesthetized rats, jejunal villous blood flow was measured in surface capillaries using fluorescence microscopy. Stasis of superficial capillary blood flow was induced by combined topical and i.v. indomethacin (100 microg/mL, 2.8 x 10(-4) M). To examine the effect of CL on blood stasis, CL was applied either i.v. (1 mg/kg) or luminally (100 microg/mL, 2.5 x 10(-5)M) at the onset of stasis. Prophylactic protection was assessed by giving i.v. CL simultaneously with indomethacin. Results were compared with controls which received luminal saline applied at blood stasis. The effect of i.v. CL (1 mg/kg) alone, or luminal CL (100 microg/mL) alone on basal villous blood flow was also examined. The small intestines were perfusion-fixed with 10% formol saline, and removed for histology, n = 5 for all groups. Luminal CL given at stasis reversed indomethacin-induced stasis within 10 min, whereas i.v. CL did not. Pretreatment with i.v. CL prevented the onset of stasis. Basal blood flow was raised slightly only by luminal CL. The beta-adrenoceptor agonist CL316,243 can protect against indomethacin-induced blood stasis in rat jejunal villi.Alimentary Pharmacology & Therapeutics 12/1998; 12(11):1121-9. DOI:10.1046/j.1365-2036.1998.00400.x · 5.48 Impact Factor