Thorac Cardiovasc Surg 2007; 55 - P_136
DOI: 10.1055/s-2007-967691

Imatinib-Mesylate in combination with RAD reduces significantly chronic rejection (CR) after orthotopic lung transplantation (LTX) in an experimental rat model

T Pühler 1, E Lesser 1, C Hass 1, M Ernst 1, B Bewig 2, H Wottge 3, J Cremer 1, S Hirt 1
  • 1University Hospital SH Campus Kiel, Cardio-Vascular Surgery, Kiel, Germany
  • 2University Hospital SH Campus Kiel, Pneumology, Kiel, Germany
  • 3University Hospital SH Campus Kiel, Immunology, Kiel, Germany

Objective: To investigate different therapeutic approaches to avoid CR we established an experimental LTX rat model (F344>WKY). Without immunosuppression in this model acute rejection (AR) is present at day 14 followed by severe CR at day 30. We analysed the influence of RAD alone and in combination with Imatinib-Mesylate (IM) towards the influence on AR and CR.

Method: After initiating AR therapy with Methyl-Prednisolone (MP) (10mg/kg/day 14–16), RAD (2.5mg/d) was administrated by gavage (i.g.) from day 14–100 in group I (n=20). In group II additionally IM was administrated i.g. from day 0–100 (n=20). In each group 5 rats were sacrified at day 20, 30, 60, 100 and syngrafts at day 100. AR/CR was graded histologically according to the ISHLT classification.

Results: In group I, MP in combination with RAD suppresses the extent of AR, however, augmentation with RAD could not avoid CR from day 60. In group II, we do not observe a reduction in the amount of AR but the appearance of chronic vascular rejection (CVR) and obliterative bronchiolitis (OB) could be reduced dramatically.

Discussion: Supplementary administration of RAD at the time point of AR was able to augment the immunosuppressive power and to reduce the extent f AR, while no preventive effect was seen in terms of OB. For the first time in this in vivo rat LTX model the application of IM, a tyrosine kinase inhibitor, from day 0 in combination with RAD could reduce the occurrence of CVR and OB significantly.