Hydrogen sulfide attenuates intestinal ischemia-reperfusion injury when delivered in the post-ischemic period.
OBJECTIVE
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 µM 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 µM, or 100 µM 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 µM HS, and at the 2 h time point with 100 µM HS (P < 0.017). In vivo, after 1 h ischemia, qualitative reduction of injury was noted with 10 µM and 100 µM; after 2 h ischemia, reduction was noted with 10 µM but not 100 µM; 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 µM (P = 0.129).


CONCLUSIONS
Hydrogen sulfide provides significant protection to intestinal tissues in vitro and in vivo when delivered after the onset of ischemia.
Henderson
Peter W
PW
Laboratory for Bioregenerative Medicine and Surgery, Department of Surgery, Weill Cornell Medical College, New York, New York 10065, USA.
Weinstein
Andrew L
AL
Sohn
Allie M
AM
Jimenez
Natalia
N
Krijgh
David D
DD
Spector
Jason A
JA
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000627:therapeutic use*; D007410:Intestinal Diseases / Q000188:drug therapy* / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007579:Jejunal Diseases / Q000188:drug therapy* / Q000473:pathology; D007583:Jejunum / Q000098:blood supply; D008297:Male; D010784:Photomicrography; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D006862:Hydrogen Sulfide