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European Journal of Cardio-Thoracic Surgery, Vol 5, 266-271, Copyright © 1991 by European Association for Cardio-thoracic Surgery
M Zenati, AJ Duncan, GJ Burckart, M Schaper, SA Yousem, BP Griffith and D Casarotto
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 less than 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 less than
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.
ARTICLES
Immunosuppression with aerosolized cyclosporine for prevention of lung rejection in a rat model
Division of Cardiac Surgery, University of Verona, Italy.
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S. N. Mitruka, S. M. Pham, A. Zeevi, S. Li, J. Cai, G. J. Burckart, S. A. Yousem, R. J. Keenan, and B. P. Griffith Aerosol cyclosporine prevents acute allograft rejection in experimental lung transplantation J. Thorac. Cardiovasc. Surg., January 1, 1998; 115(1): 28 - 37. [Abstract] [Full Text] [PDF] |
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