Effects of FK409 on intestinal ischemia-reperfusion injury and ischemia-induced changes in the rat mucosal villus microcirculation.
BACKGROUND
The small intestine is extremely sensitive to ischemia-reperfusion (I/R) injury and a range of microcirculatory disturbances contribute to tissue damage. Nitric oxide (NO) seems to be involved in tissue protection after I/R injury. This study therefore assessed the effects of the NO donor, FK409, on intestinal I/R injury and changes induced in intestinal microcirculation.


METHODS
PVG rats were subjected to 30-min intestinal ischemia with a subgroup of animals receiving FK409 (10 mg/kg i.v.) 30 min before ischemia and 30 min postreperfusion. Controls underwent sham surgery. The mucosal surface was visualized via an incision made in an exteriorized ileal segment and FITC-BSA or acridine orange was used to quantitate macromolecular leak (MML) and leukocyte adhesion, respectively. MML from, and numbers of adherent leukocytes within, individual villi were determined every 15 min for 2 hr after removal of the vessel clamp. Heart rate and mean blood pressure (mBP) were monitored throughout the experiment.


RESULTS
Eleven of 12 untreated animals subjected to intestinal I/R injury failed to survive the 2 hr reperfusion period, whereas all 12 FK409-treated animals survived. MML and leukocyte adhesion were increased in untreated animals (P<0.001), and blood flow stasis eventually ensued. Although FK409 decreased mBP (P<0.001), MML and leukocyte adhesion were significantly (P<0.001) reduced, and villus blood flow was maintained throughout the observation period.


CONCLUSIONS
FK409 prevented mortality after intestinal I/R, significantly reduced leukocyte adhesion, and maintained blood flow after intestinal ischemia and may therefore be of value in reducing tissue damage and improving outcome after small bowel transplantation.
Kalia
N
N
Section of Surgical and Anesthetic Sciences, Division of Clinical Sciences (CSUH), Royal Hallamshire Hospital, Sheffield, S10 2JF, UK.
Pockley
A G
AG
Wood
R F
RF
Brown
N J
NJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007413:Intestinal Mucosa / Q000098:blood supply*; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000473:pathology* / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008871:Microvilli / Q000473:pathology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009574:Nitro Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000473:pathology* / Q000503:physiopathology*; D016019:Survival Analysis
D020030:Nitric Oxide Donors; D009574:Nitro Compounds; C061872:FK 409