Rpn. Willoughby et al., INTESTINAL MUCOSAL PERMEABILITY TO CR-51-ETHYLENEDIAMINETETRAACETIC ACID IS INCREASED AFTER BILATERAL LOWER-EXTREMITY ISCHEMIA-REPERFUSION IN THE RAT, Surgery, 120(3), 1996, pp. 547-553
Background. Despite successful revascularization of ischemic extremiti
es, multiogran dysfunction syndrome develops in some patients. Mechani
sms responsible for this are not known; however, the gastrointestinal
tract has been implicated as a possible mediator. Our objective was to
demonstrate increased intestinal mucosal permeability after bilateral
hindlimb ischemia-reperfusion (I-R) in a rodent model. Methods. Sixte
en male Wistar rats were randomized either to 4 hours of bilateral hin
dlimb tourniquet ischemia and 24 hours of reperfusion (n = 8) or contr
ol groups (n = 8). The animals received 10 mu Ci Cr-51-ethylenediamine
tetraacetic acid (EDTA) by gavage, and excretion was measured in urine
collected every 8 hours in 16 animals and every 4 hours in 8 animals.
Arterial blood pressure was monitored continuously. Intravenous norma
l saline solution (3 ml/hr) with fentanyl (2 mu g/100 gm/hr) was conti
nuously administered. Immediately before death complete blood count an
d levels of arterial lactate, creatinine, and urea were obtained. Mese
nteric lymph nodes were harvested from the ileocecal region and cultur
ed. Distal small bowel and proximal colon were preserved for histologi
c analysis. An additional 11 rats, six experimental and five control,
were evaluated for mesenteric lymph node cultures only. Results. Urina
ry excretion of Cr-51-EDTA was significantly greater in the I-R group
between 0 and 8 hours (p < 0.02) and 8 to 16 hours (p < 0.0002) of rep
erfusion. This increase occurred as early as 4 to 8 hours of reperfusi
on (p < 0.0001). Urine volume in the I-R group was significantly reduc
ed during 0 to 4 hours of reperfusion (p < 0.002). Hemoglobin in and l
actate level were significantly different in the I-R growth. Leukocyte
and platelet counts, levels of creatinine and urea, and colony counts
from mesenteric lymph nodes were similar in I-R and control groups. B
linded histologic analysis of bowel segments did not reveal morphologi
c differences. Conclusions. Bilateral hindlimb I-R produces remote int
estinal mucosal injury shown by significantly increased permeability t
o Cr-51-EDTA. Such increased mucosal permeability may be important in
the development of multiorgan dysfunction syndrome in patients who sus
tain lower extremity I-R injury.