Aerosol cyclosporine prevents acute allograft rejection in experimental lung transplantation

The Journal of Thoracic and Cardiovascular Surgery
S N MitrukaB Griffith

Abstract

The incidence of acute rejection and the morbidity of systemic cyclosporine (INN: cyclosporine) after lung transplantation is significant. Experimental evidence suggests that the allograft locally modulates the immune mechanisms of acute rejection. The purpose of this study was to determine whether aerosolized cyclosporine would prevent acute cellular rejection, achieve effective graft concentrations with low systemic drug delivery, and locally affect production of the inflammatory cytokines involved in acute rejection. Unilateral orthotopic left lung transplantation was performed in 64 rats (ACI to Lewis), which were divided into eight groups (each group, n = 8): group A, no treatment; groups B to D, aerosol cyclosporine 1 to 3 mg/kg per day, respectively; group E to H, systemic cyclosporine 2, 5, 10, and 15 mg/kg per day, respectively. After the animals were killed on postoperative day 2, 4, or 6, the transplanted lung, native lung, spleen, and blood were collected. Histologic studies, high-pressure liquid chromatography for trough cyclosporine concentrations, and reverse-transcriptase polymerase chain reaction for cytokine gene expression were performed. Untreated animals showed grade 4 rejection by postoperative day 6. Aero...Continue Reading

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Citations

Jan 5, 2000·The Annals of Thoracic Surgery·G V LetsouJ C Waldrep
Oct 25, 2000·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·S N MitrukaG J Burckart
Dec 27, 2007·Journal of Aerosol Medicine : the Official Journal of the International Society for Aerosols in Medicine·Tao WangNancy Turner
Apr 12, 2011·Journal of Aerosol Medicine and Pulmonary Drug Delivery·Ralph NivenHoward Raff
Jul 3, 2004·The Journal of Clinical Investigation·Marina OstroukhovaAnuradha Ray
Oct 12, 1999·Journal of Clinical Pharmacology·A Lo, G J Burckart
Dec 25, 2010·Nanomedicine·Fernanda AndradeBruno Sarmento
May 1, 2011·Therapeutic Delivery·Javier O MoralesRobert O Williams
Sep 18, 2008·Drug Development and Industrial Pharmacy·Alan B WattsJay I Peters
Jul 31, 2009·Drug Development and Industrial Pharmacy·Justin A Tolman, Robert O Williams
Jul 25, 2006·Expert Opinion on Investigational Drugs·Gilbert J Burckart
Mar 21, 2008·Journal of Pharmaceutical Sciences·Jasmine M TamKeith P Johnston
May 7, 2009·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Gerrit S ZijlstraHenderik W Frijlink
Jan 30, 2007·The Journal of Thoracic and Cardiovascular Surgery·Noboru IdeMikiro Nakashima
Aug 29, 2006·Drug Discovery Today·Jagdish L ItaliaM N V Ravi Kumar
Sep 26, 2006·Advanced Drug Delivery Reviews·T E Corcoran
Mar 31, 2005·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Shinji NakashimaTomio Abe
Jul 2, 2003·The Annals of Otology, Rhinology, and Laryngology·Marcus HaugMarshall Strome
Mar 12, 2005·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Shinji NakashimaWilliam M Baldwin

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