Donor-specific blood transfusion prolongs cardiac allograft survival in rats by low nitric oxide production and elevated serum levels of prostaglandin E(2).
Donor-specific blood transfusion (DST) improves allograft survival, although the exact mechanism(s) is not completely understood. The purpose of this study was to determine the role of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in DST-protective effects, using a rat cardiac transplantation model. Lewis rats (RT-1(1)) were transfused with fully allogeneic ACI rats (RT-l(a)) blood (DST group) or Lewis syngeneic blood (ST) through the portal vein 7 days prior to allogeneic cardiac transplantation. Posttransplantation, aminoguanidine (AG)-treated rat received continuous intravenous infusion of AG, an inhibitor of inducible nitric oxide synthase (iNOS). The survival times of grafted hearts were 5.7+/-0.5, 6.8+/-0.8 and 9.2+/-1.2 days in ST, ST/AG, and DST groups (n=6 for each group), respectively. Inhibition of iNOS in ST/AG group prolonged allograft survival, but it was shorter than that in DST rats. Serum nitrite/nitrate levels on postgrafting day 5 were significantly higher in ST than in ST/AG and DST groups, but were similar in ST/AG and DST groups. These results were confirmed by immunohistochemical staining with anti-iNOS antibody. Serum PGE(2) concentrations in DST rats were significantly higher than in ST and ST/AG groups. Our results suggest that DST prolongs graft survival by enhanced production of PGE(2) with a resultant suppression of immune activation. In addition, DST-induced prolongation of graft survival may be partially mediated by NO suppression.
Inuzuka
Shu
S
Department of Urology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki city, Japan.
Koga
Shigehiko
S
Nishikido
Masaharu
M
Miyata
Yasuyoshi
Y
Kanda
Shigeru
S
Shimokawa
Isao
I
Tanaka
Mitsuko
M
Saito
Yutaka
Y
Kanetake
Hiroshi
H
D000818:Animals; D001803:Blood Transfusion; D015232:Dinoprostone / Q000097:blood*; D006085:Graft Survival; D016027:Heart Transplantation; D007150:Immunohistochemistry; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D015232:Dinoprostone