Superior mesenteric artery blood flow and indomethacin- induced
intestinal injury and inflammation.
Battarbee, Harold D., Matthew B. Grisham, Glenda G. Johnson, and James
H. Zavecz.
Departments of Physiology and Pharmacology, Louisiana State
University Medical Center in Shreveport, Shreveport, LA 71130
-3932
APStracts 3:0077G, 1996.
Intestinal injury caused by nonsteroidal anti-inflammatory drugs
(NSAIDs) is associated with increased mucosal permeability,
microvascular injury, focal intravascular thrombus formation, fibrin
deposition, and neutrophil infiltration. Ulcerations and adhesions
are also prominent features of this injury. Although NSAID-induced
inhibition of prostaglandin formation has been suggested to produce
ischemic injury and inflammation, no studies have directly assessed
intestinal blood flow in experimental NSAID-induced enteropathy. This
study's objective was to test the hypothesis that indomethacin
-induced small bowel injury and inflammation result from intestinal
ischemia. Using pulsed Doppler flowmetry, conscious rats' superior
mesenteric artery blood flow was continuously monitored following
doses of indomethacin known to promote acute and then chronic small
bowel inflammation (7.5 mg/kg, 2 sc doses spaced 24 hrs apart). After
72 hrs, rats were anesthetized and a section of small bowel was
removed for histology and intestinal myeloperoxidase activity
measurements. The mean arterial blood pressure was not affected until
32 hrs following indomethacin, when it decreased 20% (p<0.05 to
<0.01). Sustained blood flow changes first occurred at 20 hrs,
when an increase of 15% (p<0.01) was observed, while flow
resistance decreased. Flow resistance continued to decrease for the
remainder of the 72 hr period, and there was an accompanying blood
flow increase to +40% (p<0.05 to <0.01). Intestinal ulcers
developed in 86% of the Indomethacin-treated rats. Adhesions,
dilation, and thickening of the distal jejunum and proximal ileum
were observed in most indomethacin-treated rats. Histological grading
of intestinal injury yielded scores of 7.1 +/- 1.2 and zero for
indomethacin-treated rats and vehicle-injected rats, respectively
(p<0.01). Myeloperoxidase activity was greater in indomethacin
-treated rats (6.7 +/- 1.9 vs 1.8 +/- 0.3 U/cm, p<0.05). These
results suggest that Indomethacin-induced enteropathy is associated
with an increase, not a decrease, in superior mesenteric artery blood
flow. Therefore, ischemia does not appear to be a mechanism by which
subcutaneous indomethacin administration produces small intestinal
injury and inflammation.
Received 22 June 1995; accepted in final form 18 March 1996.
APS Manuscript Number G266-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 16 April 96