IMMUNOSUPPRESSION WITH AEROSOLIZED CYCLOSPORINE FOR PREVENTION OF LUNG REJECTION IN A RAT MODEL

被引：18

作者：

ZENATI, M

DUNCAN, AJ

BURCKART, GJ

SCHAPER, M

YOUSEM, SA

GRIFFITH, BP

CASAROTTO, D

机构：

[1] Division of Cardiac Surgery, University of Verona

[2] Departments of Surgery, University of Pittsburgh

[3] Pharmacology, University of Pittsburgh

[4] Environmental Health Sciences, University of Pittsburgh

[5] Pathology, University of Pittsburgh

来源：

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY | 1991年 / 5卷 / 05期

关键词：

LUNG TRANSPLANTATION; LOCAL IMMUNOSUPPRESSION; AEROSOL; ALLOGRAFT REJECTION;

D O I：

10.1016/1010-7940(91)90175-J

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The efficacy of local delivery of aerosol cyclosporine (CsA) for prevention of lung rejection was compared with the intramuscular route (IM) in a fully allogeneic rat model (BN/LEW) of lung transplantation (LTx). Control rats (group 1, n = 6) received no CsA after LTx. Rats in group 2 (n = 10) received 4 doses of CsA in olive oil (25 mg/kg) intramuscularly starting on postoperative day (POD) 0. Group 3 (n = 9) was treated with aerosolized CsA for 3 h/day for 7 days starting on POD 0. All animals were sacrificed on POD 6. Transplanted lungs were graded histologically in a blind manner on a 0-4 scale. Control animals all showed grade 4 rejection. i.m. CsA therapy reduced lung rejection with a rejection grade of 1.8 +/- 0.35 (mean +/- SD) but was associated with a 50% incidence of pneumonia. Aerosol CsA provided better control of rejection with a rejection grade of 1.2 +/- 0.4 (group 3 vs. group 2: P < 0.05 Wilcoxon) and none of these animals had penumonia. Trough blood levels of CsA were significantly lower in the group treated with aerosolized CsA when compared with the IM group (P < 0.05). Therefore we conclude that: (1) aerosol CsA is effective in preventing lung allograft rejection following lung transplantation in rats, and (2) local delivery of aerosol CsA is superior to the i.m. route because better control of rejection is achieved with a lower systemic delivery of CsA.

引用

页码：266 / 272

页数：7

共 23 条

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