HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ide, N. Articles by Nakashima, M. Search for Related Content PubMed PubMed Citation Articles by Ide, N. Articles by Nakashima, M.

J Thorac Cardiovasc Surg 2007;133:548-553
© 2007 The American Association for Thoracic Surgery

Cardiothoracic Transplantation

Efficacy and safety of inhaled tacrolimus in rat lung transplantation

^a Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
^b Division of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan.

Received for publication March 22, 2006; revisions received July 17, 2006; accepted for publication September 5, 2006.

^_* Address for reprints: Takeshi Nagayasu, MD, Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan (Email: nagayasu{at}net.nagasaki-u.ac.jp).

OBJECTIVE: Because acute rejection is the most important cause of chronic rejection in lung transplantation, the use of conventional systemic immunosuppression to improve long-term survival needs to be reassessed. The aim of this study was to investigate the efficacy and safety of inhaled tacrolimus for preventing acute rejection of rat lung allografts.

METHODS: Orthotopic left lung transplantation was performed in rats that were divided into 6 groups: control group received no treatment; groups 1.0-IM, 0.5-IM, and 0.3-IM received tacrolimus by intramuscular injection at 1.0, 0.5, and 0.3 mg/(kg · d), respectively; and groups 12-IT and 6-IT received 12 and 6 puffs of inhaled tacrolimus 3 times per day, respectively. Allografts were studied histologically. Whole blood and allograft tacrolimus concentrations were determined.

RESULTS: In groups 1.0-IM and 12-IT, histologic grade of the graft showed significantly less rejection than in the other groups. The blood tacrolimus concentration in group 12-IT (4.87 ng/mL) was significantly lower than that in group 1.0-IM (13.05 ng/mL, P = .0017) on postoperative day 7. Higher allograft tacrolimus concentrations were achieved in group 1.0-IM (478.0 ng/g) than in group 12-IT (270.4 ng/g, P = .009). Weight loss and diarrhea in group 12-IT were less severe than in the groups that received systemic tacrolimus. The proliferating cell nuclear antigen index in bronchus-associated lymphoid tissue cells was significantly lower in group 12-IT than in group 1.0-IM (P = .0209).

CONCLUSION: Local immunotherapy with inhaled tacrolimus has great potential for controlling pulmonary allograft rejection in clinical lung transplantation because it has fewer side effects than systemic immunosuppressive agents.