EXPERIMENTAL GRAFT CORONARY-ARTERY DISEASE IN A MURINE HETEROTOPIC CARDIAC TRANSPLANT MODEL

被引:32
作者
HIROZANE, T [1 ]
MATSUMORI, A [1 ]
FURUKAWA, Y [1 ]
SASAYAMA, S [1 ]
机构
[1] KYOTO UNIV,FAC MED,DEPT INTERNAL MED,DIV 3,SAKYO KU,KYOTO 606,JAPAN
关键词
CORONARY DISEASE; TRANSPLANTATION; REJECTION;
D O I
10.1161/01.CIR.91.2.386
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background The development of immunosuppressive therapy has brought about a remarkable decrease in the risk of acute cardiac allograft rejection; however, the major cause of patient death or retransplantation after the first postoperative year is coronary artery disease (CAD) in the graft. The pathogenesis and management of CAD are still not clearly established. Methods and Results To make an animal model of CAD, we performed primary vascularized heterotopic cardiac transplantation using mice. Inbred strains, sharing major histocompatibility antigens but differing in minor antigens, were selected. DBA/2 mice (H-2(d)) served as donors and B10.D2 mice (H-2(d)) as recipients. Viability of the cardiac grafts was assessed by abdominal palpation. Eight of twelve cardiac allografts (67%) survived for 10 weeks after operation without any immunosuppressive therapy. Allografts rejected within 4 weeks showed acute rejection histologically, whereas allografts surviving more than 4 weeks displayed intimal hyperplasia in the coronary arteries, together with interstitial and perivascular fibrosis. The severity of intimal thickening in the graft coronary artery was then assessed by point counting. In allografts surviving for 70 days, intima comprised approximately 42% of the graft arterial wall, whereas in DBA/2 and B10.D2 syngeneic grafts, it comprised approximately 13%. A significant difference in percentage was observed between the intima area of allografts and that of syngrafts (P<.01, ANOVA). Long-term oral administration of cyclosporine at a dose of 40 mg/kg per day decreased the intima area to 34% (P<.05 versus nontreated allografts, ANOVA); however, this dose did not affect the incidence of arterial lesions. Conclusions The histopathological features of DBA/2 allografts surviving for 10 weeks in B10.D2 recipient mice mimicked those in human CAD. Using this animal model, the beneficial effect of low-dose cyclosporine therapy on CAD was demonstrated, although this effect seemed to be limited. This DBA/2-B10.D2 mouse heterotopic cardiac transplant model provides valuable results for future studies of the disease.
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页码:386 / 392
页数:7
相关论文
共 35 条
  • [1] EXPERIMENTAL GRAFT ARTERIOSCLEROSIS .1. THE LEWIS-TO-F-344 ALLOGRAFT MODEL
    ADAMS, DH
    TILNEY, NL
    COLLINS, JJ
    KARNOVSKY, MJ
    [J]. TRANSPLANTATION, 1992, 53 (05) : 1115 - 1119
  • [2] ADAMS DH, 1987, CIRCULATION, V76, P314
  • [3] ALONSO DR, 1977, AM J PATHOL, V87, P415
  • [4] BERNABEU M, 1993, TRANSPLANT P, V25, P17
  • [5] BIEBER CP, 1981, TRANSPLANT P, V13, P207
  • [6] BILLINGHAM ME, 1989, TRANSPLANT P, V21, P3665
  • [7] BILLINGHAM ME, 1987, TRANSPLANT P, V19, P19
  • [8] HEART IN SYSTEMIC LUPUS-ERYTHEMATOSUS AND CHANGES INDUCED IN IT BY CORTICOSTEROID-THERAPY - STUDY OF 36 NECROPSY PATIENTS
    BULKLEY, BH
    ROBERTS, WC
    [J]. AMERICAN JOURNAL OF MEDICINE, 1975, 58 (02) : 243 - 264
  • [9] CHORDERA A, 1978, INT J CLIN PHARM TH, V16, P357
  • [10] Corry RJ, 1973, TRANSPLANTATION, V16, P344