Hydrogen sulfide attenuates intestinal ischemia-reperfusion injury when delivered in the post-ischemic period

Background and Aim: To investigate whether pharmacologic post-conditioning of intestinal tissue with hydrogen sulfide (HS) protects against ischemia reperfusion injury (IRI). Methods: In vitro, enterocytes were made hypoxic for 1, 2, or 3 h, treated with media containing between 0 and 100 mu M HS 20 min prior to the end of the hypoxic period, then returned to normoxia for 3 h. An apoptotic index (AI) was determined for each time point and (HS). In vivo, jejunal ischemia was induced in male Sprague-Dawley rats for 1, 2, or 3 h; 20 min prior to the end of the ischemic period animals were given an intravenous injection of NaHS sufficient to raise the bloodstream concentration to 0, 10 mu M, or 100 mu M HS. This was followed by jejunal reperfusion for 3 h, histologic processing, and measurement of villus height. Results: In vitro, there was a significant decrease in AI compared with non-HS-treated control at all time points after treatment with 10 mu M HS, and at the 2 h time point with 100 mu M HS (P < 0.017). In vivo, after 1 h ischemia, qualitative reduction of injury was noted with 10 mu M and 100 mu M; after 2 h ischemia, reduction was noted with 10 mu M but not 100 mu M; and after 3 h ischemia, there was no injury reduction. HS treatment resulted in significant quantitative preservation (P < 0.05) of villus height at all time points and doses, except for 3 h ischemia and delivery of 100 mu M (P = 0.129). Conclusions: Hydrogen sulfide provides significant protection to intestinal tissues in vitro and in vivo when delivered after the onset of ischemia.