Total warm ischemia and reperfusion impairs flow in all rat gut layers but increases leukocyte-vessel wall interactions in the submucosa only.
OBJECTIVE
To study the effect of warm ischemia and reperfusion (I/R) on local perfusion and leukocyte-vessel wall interactions in vivo in all small bowel layers, and to quantify small bowel tissue injury histologically and by measuring intestinal fatty acid binding protein (I-FABP) release from the enterocytes.


BACKGROUND
Gut injury as a result of I/R plays a pivotal role in a variety of clinical conditions, such as small bowel transplantation, heart or aortic surgery, and (septic) shock. The precise mechanism behind I/R injury and the role of microvascular changes remain unclear. The influence of warm I/R of the gut on microvascular parameters in the different gut layers has not been studied before.


METHODS
Anesthetized Lewis rats were either subjected to 30 minutes of ischemia and 1 hour of reperfusion or sham-treated as controls. After ligating the inferior mesenteric artery, total warm ischemia was induced by clamping the superior mesenteric artery. Intravital video microscopic measurements were obtained at intervals. Tissue injury of the small bowel and other organs was histologically evaluated afterward. In addition, plasma levels of I-FABP were determined to measure enterocyte damage.


RESULTS
After ischemia, mean red blood cell velocity decreased significantly in all layers of the small bowel, but no diameter changes were observed. Leukocyte-vessel wall interactions increased in the submucosa but not in the muscle layers. Plasma levels of I-FABP significantly increased from 30 minutes of reperfusion onward. The intestinal mucosa was severely injured; no histologic damage was detected in other tissues.


CONCLUSIONS
This is the first in vivo study showing that total warm ischemia of the rat gut impairs perfusion in the whole small bowel, whereas leukocyte-vessel wall interactions increase in the submucosal layer only. Therefore, the early inflammatory response to I/R seems to be limited to the submucosa. Both microvascular effects may have contributed to the severe morphologic and functional mucosal injury observed after I/R.
Beuk
R J
RJ
Department of Surgery, Cardiovascular Research Institute Maastricht (CARIM), University Hospital Maastrict, The Netherlands.
Heineman
E
E
Tangelder
G J
GJ
Quaedackers
J S
JS
Marks
W H
WH
Lieberman
J M
JM
oude Egbrink
M G
MG
D000818:Animals; D015415:Biomarkers; D001783:Blood Flow Velocity / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000276:immunology; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000276:immunology / Q000473:pathology; D007421:Intestine, Small / Q000098:blood supply* / Q000473:pathology; D007962:Leukocytes / Q000276:immunology* / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000473:pathology; D018996:Myelin P2 Protein / Q000378:metabolism*; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology
D015415:Biomarkers; D002352:Carrier Proteins; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins