Impact of the severity of acute rejection in the early phase after rat lung transplantation on the effectiveness of mycophenolate mofetil to treat chronic allograft rejection

Abstract

MMF significantly reduced AR and CR after rat LTX. However, only allografts with no or mild AR at the time of drug initiation benefited from MMF treatment. In addition, the appearance of early signs of fibroproliferative alterations in the airway structures might prevent a successful long-term outcome.

Effects of azithromycin and tanomastat on experimental bronchiolitis obliterans

“…The histologic picture was not improved after 4 weeks of AZI versus control allografts. Chronic vascular and airway changes were slightly attenuated after 8 weeks in animals receiving AZI with reduced collagen deposition in EVG stains (Figure 2), but without statistically significant change in histologic score 18 versus controls (Figure 3, Table 1). The chronic airway rejection score in AZI-treated animals did not change significantly between 4 and 8 weeks after transplantation, whereas it significantly worsened from 4 to 8 weeks after transplantation in control allografts (P ¼ .041).…”

“…Histologic findings were attributed to groups of absent, low-grade, high-grade, and fibrotic chronic vascular and airway changes as described. 18 The categories of chronic vascular rejection were as follows: low-grade chronic vascular rejection: occlusion of small vessels with mononuclear infiltrate and fibrous tissue; high grade: vascular sclerosis of small and medium-sized arteries and veins with fibrointimal thickening; and fibrotic chronic vascular changes: complete allograft fibrosis. The categories of chronic airway rejection were as follows: low-grade chronic airway rejection: initial signs of intraluminal granulation tissue polyps in more than one terminal bronchiole or loose subepithelial fibrin structures around terminal bronchioles; high grade: BO with fibrosis of the submucosa of terminal bronchioles with partial or complete luminal occlusion; and chronic fibrotic airway changes: complete allograft fibrosis.…”

“…Transplantation of Fischer F344 lungs to Wistar Kyoto (WKY) rats leads to acute rejection and subsequent chronic changes with predominant vascular rejection, but BO-like lesions develop in about 70% to 80% of the animals at 60 days following transplantation. [17][18][19] In the current study, we investigated the effects of prophylactic AZI on BO in this model at 4 and 8 weeks posttransplant, corresponding to acute inflammatory and chronic stages of allograft dysfunction. No immunosuppression other than a single dose of prednisolone at transplantation to avoid hyperacute rejection on the first day was given to determine the immunomodulatory effects of AZI alone.…”