Ischemic preconditioning ameliorates ischemia- and reperfusion-induced intestinal epithelial hyperpermeability in rats

We hypothesized that ischemic preconditioning (IPC) would ameliorate ischemia (I) and reperfusion (R)-induced intestinal mucosal hyperpermeability and that this effect would be diminished by lowering local adenosine concentrations using adenosine deaminase (ADA). The small intestine of anesthetized rats (group 1; n = 6) was divided into six 10-cm segments (A(1)-F-1) each perfused by a different set of mesenteric branches. Segments D-1-F-1 were subjected to 3 cycles of IPC (2 min 1/5 min R). Segments A(1), B-1, and C-1 were excised at baseline, after 60 min of 1 (160), and after 60 min of 1 followed by 60 min of R (160/R60), respectively. Segment D-1 was excised immediately after the last cycle of IPC, E-1 was excised at 160 after IPC, and F-1 was excised at 160/R60 after IPC. In group 2 (n = 6), the intestine was divided into five 10-cm vascularly isolated segments (A(2)-E-2). Segment A(2) was resected at baseline. The lumen of the remaining segments was filled with ADA (32 U/50 cm). Segment B-2 was removed at the end of the experiment having been exposed to ADA for 150 min (ADA(150)). Segments C-2, D-2, and E-2 were subjected to IPC. Segment C-2 was excised immediately thereafter. Segments D-2 and E-2 were excised at 160 and 160/R60, respectively. Intestinal permeability to fluorescein isothiocyanate-labeled dextran (molecular weight 4000 D) was assessed ex vivo by using an everted gut sac method. IPC ameliorated intestinal hyperpermeability induced by 160 (43.0 +/- 7.6 vs. 70.4 +/- 8.3 nL/min/cm(2); P = 0.024) and 160/R60 (20.2 +/- 3.7 vs. 69.5 +/- 10.8 nL/min/cm(2); P = 0.003). IPC prevented ischemia-induced reduction in villus height. Treatment with ADA partially reversed the protective effect of IPC on the changes in permeability and villus height induced by I/R. We conclude that IPC partially protects against mucosal barrier dysfunction in rats subjected to mesenteric I/R. Adenosine is a mediator of IPC in the gut mucosa, but other factors also may be important.