Post-ischaemic restituted intestinal mucosa is more resistant to further ischaemia than normal mucosa in the pig.
OBJECTIVE
Ischaemic preconditioning may protect the intestine from subsequent prolonged ischaemia. This study evaluates whether a much longer initial ischaemia, encountered clinically, may modify intestinal resistance to further ischaemia in a pig model.


METHODS
After cross-clamping of the superior mesenteric artery for 1 h, the intestine was either reperfused for 8 h or a second cross-clamping for 1 h was performed at 4 h of reperfusion. Based on microarray analysis of intestinal samples at 1, 4 and 8 h of reperfusion, mRNA of selected genes was measured with QRT-PCR.


RESULTS
The first ischaemic period caused exfoliation of surface epithelial cells from the basement membrane comprising about 90 % of the villi tips, a marked increase in permeability and depletion of ATP. The second ischaemic challenge caused about 30 % less denudation of the basement membrane (p = 0.008), no increase in permeability (p = 0.008) and less depletion of ATP (p = 0.039). mRNAs for superoxide dismutase 2, heat shock proteins and signal transducer and activator of transcription 3, which may protect against ischaemia/reperfusion injury, were up-regulated throughout the reperfusion period. mRNAs for matrix metalloproteinase 1, connexin 43 and peripheral myelin 22, which may be associated with cell migration or tight junctions, showed a particular up-regulation at 4 h of reperfusion.


CONCLUSIONS
One hour of initial ischaemia followed by 4 h of reperfusion is associated with increased intestinal resistance to further ischaemia. The differential regulation of genes identified in this study provides working hypotheses for mechanisms behind this observation.
Juel
Ingebjørg S
IS
Department of Surgery, St. Olav University Hospital, NO-7006 Trondheim, Norway. ingebjorg.juel@ntnu.no
Solligård
Erik
E
Tvedt
Kåre E
KE
Skogvoll
Eirik
E
Jynge
Per
P
Beisvag
Vidar
V
Erlandsen
Sten Even
SE
Sandvik
Arne K
AK
Aadahl
Petter
P
Grønbech
Jon Erik
JE
D000818:Animals; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000098:blood supply / Q000473:pathology*; D007511:Ischemia / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012039:Regional Blood Flow