Preservation injury and acute rejection of rat intestinal grafts: protection afforded by pyruvate.
Pyruvate has been shown to prevent intestinal mucosal injury after ischemia-reperfusion. The aim of the present study was to determine whether pyruvate can (1) prevent postreperfusion mucosal injury occurring after intestinal preservation and subsequent transplantation and (2) exert a protective effect on the intestinal graft mucosa during acute rejection. Preservation mucosal injury was evaluated, after 2 hours of reperfusion, by comparing grafts transplanted in a rat syngeneic combination (ACI to ACI) after 2 hours of cold preservation using pyruvate (n = 6) or placebo (n = 6). Mucosal parameters obtained during acute rejection (allogeneic combination: ACI to Lewis) were compared between placebo-treated (n = 6) and pyruvate-treated (n &equals 6) animals. Tissue injury was evaluated by histopathologic examination, oxygen free radical production by luminol-enhanced chemiluminescence, and degree of neutrophil infiltration by myeloperoxidase staining. After reperfusion of the preserved grafts and during acute rejection, mucosal oxygen free radical levels and the number of infiltrating neutrophils were significantly (P <0.05) increased in the untreated grafts, whereas there was a statistically significant inhibition of these parameters in those treated with pyruvate. Mucosal injury, seen after reperfusion of the preserved grafts, was prevented by pyruvate. The histopathologic abnormalities observed in the untreated grafts during rejection were also significantly reduced by pyruvate. Treatment with pyruvate before cold preservation of intestinal grafts, in this rat model, reduced reperfusion mucosal injury, neutrophil infiltration, and oxygen free radical production. Oxygen free radicals were produced in the mucosa of the graft during acute rejection and their production was reduced by pyruvate, which exerted a protective effect on the rejecting allograft mucosa.
Cicalese
L
L
Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Subbotin
V
V
Rastellini
C
C
Stanko
R T
RT
Rao
A S
AS
Fung
J J
JJ
D000208:Acute Disease; D000818:Animals; D005609:Free Radicals / Q000378:metabolism; D006084:Graft Rejection / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology / Q000637:transplantation*; D008297:Male; D009926:Organ Preservation; D019289:Pyruvic Acid / Q000627:therapeutic use*; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*
D005609:Free Radicals; D017382:Reactive Oxygen Species; D019289:Pyruvic Acid