The effect of ischaemic postconditioning on mucosal integrity and function in equine jejunal ischaemia.

Abstract

Ischaemic postconditioning (IPoC) has been shown to ameliorate ischaemia reperfusion injury in different species and tissues. To assess the feasibility of IPoC in equine small intestinal ischaemia and to assess its effect on histomorphology, electrophysiology and paracellular permeability. Randomised in vivo experiment. Experimental jejunal ischaemia was induced for 90min in horses under general anaesthesia. In the control group (C; n=7), the jejunum was reperfused without further intervention. In the postconditioning group (IPoC; n=7), reocclusion was implemented following release of ischaemia by clamping the mesenteric vessels in three cycles of 30seconds. This was followed by 120minutes of reperfusion in both groups. Intestinal microperfusion and oxygenation was measured during IPoC using spectrophotometry and Doppler flowmetry. Histomorphology and histomorphometry of the intestinal mucosa were assessed. Furthermore, electrophysiological variables and unidirectional flux rates of 3 H-mannitol were determined in Ussing chambers. Western blot analysis was performed to determine the tight junction protein levels of claudin-1, claudin-2 and occludin in the intestinal mucosa. Comparisons between the groups and time points were performed using a two-way repeated measures analysis of variance (ANOVA) or non-parametric statistical tests for the ordinal and not normally distributed data (significance P<.05). IPoC significantly reduced intestinal microperfusion during all clamping cycles yet affected oxygen saturation only during the first cycle. After reperfusion, Group IPoC showed significantly less mucosal villus denudation (mean difference 21.5%, P=.02) and decreased mucosal-to-serosal flux rates (mean difference 15.2nM/cm2 /h, P=.007) compared to Group C. There were no significant differences between the groups for the other tested variables. Small sample size, long-term effects were not investigated. Following IPoC, the intestinal mucosa demonstrated significantly less villus denudation and paracellular permeability compared to the untreated control group, possibly indicating a protective effect of IPoC on ischaemia reperfusion injury.