The murine orthotopic single lung transplantation model for chronic rejection: work in progress?

A preclinical model of chronic rejection after lung transplantation is essential to understand and mitigate its elusive pathophysiology. We aimed to investigate if longitudinal "in vivo" µCT imaging can help in identifying technical failures leading to graft atelectasis early on and help to evaluate the rejection process over time.We performed cuff based orthotopic single left lung transplantations. Groups consisted of isografts (n=7) (C57Bl/6 to C57BL/6) and major genetic mismatched (BALB/c to C57BL/6) allografts (n=8), with an immunosuppressive regime of Cyclosporine A (10 mg/kg/d) and corticosteroids (1 mg/kg/d). Animals underwent respiratory-gated time resolved µCT scans in a longitudinal fashion at post-operative week 1, 5 and 10.Even though, all animals recovered well after surgery, not all graft lungs were functional at week 1. Open Isografts (n=5) demonstrated normal appearing lung parenchyma at week 1, 5 and 10. Functional allografts (n=2) displayed ground glass and consolidation around the airways and blood vessels at week 1 and a progressive pattern of fibrosis at week 5 and 10. The remaining grafts (n=6) presented with high density tissue of the allograft.Longitudinal µCT scanning is possible and important for the elucidation of disease evolution. Imaging 1 week after LTx already identifies technical failure of surgery resulting in graft atelectasis and pronounced immune responses after murine LTx.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Transplantation Source Type: research