Abstract
Background. Atherosclerosis is the main lesion in allografts undergoing chronic rejection. We
investigated the effect of OP-2507 (prostaglandin I2 analogue) and OKY-046 (thromboxane A2 synthetase inhibitor) on graft atherosclerosis morphologically and the production
of eicosanoids in grafts in a rat aortic allograft model. Methods. Abdominal aortic allografts of Lewis (RT-1l) rats were transplanted orthotopically into fully major histocompatibility complex
mismatched Wistar King A/Qdj (RT-1u) rats that were subcutaneously administered OP-2507 (0.1 mg/kg/d) or OKY-046 (125
mg/kg/d), or both, with an osmotic pump. Four, 8, or 12 weeks later, the grafts were
harvested and examined histologically, and the concentration of eicosanoids in the
grafts were analyzed. Results. Lewis aortic allografts in Wistar King A recipients with no treatment displayed atherosclerosis,
which involved gradual intimal thickening and medial thinning with continuous inflammation
in adventitia. Neither OP-2507 nor OKY-046 treatment affected the intensity of adventitial
inflammation. Although inhibition of medial thinning or a decrease in medial nuclear
density was not observed, OKY-046 administration alone significantly inhibited an
increase in intimal thickness. OP-2507 administration alone significantly inhibited
a decrease in medial nuclear density and intimal thickening. Combined treatment with
OP-2507 and OKY-046 further decreased the alteration of media and intima. The ratio
of thromboxane B2 and 6-keto-prostaglandin F1α in the grafts was significantly reduced by OKY-046 but not by OP-2507 alone. Conclusions. We have demonstrated that atherosclerosis in aortic allografts is inhibited by the
continuous administration of either OP-2507 or OKY-046, and a combination of both
agents strongly increases this inhibitory effect. Amelioration of balance in eicosanoid
production in the grafts by the use of thromboxane A2 synthetase inhibitor and the simultaneous usage of stable prostaglandin I2 analogue may be a strategy for preventing atherosclerosis that results from chronic
rejection. (Surgery 2001;129:595-605.)
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Article info
Publication history
Accepted:
October 25,
2000
Footnotes
*Supported in part by the Foundation for Advancement of Clinical Medicine, Japan.
**Reprint requests: Yuji Nakafusa, MD, Department of Surgery, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
*Surgery 2001;129:595-605.
Identification
Copyright
© 2001 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
