Remote Kidney and Liver Injury After Transplantation of Lung Allografts in an Allogeneic Mouse Model

Abstract

Background

Remote organ dysfunction is common after lung transplantation and might negatively affect the outcome. The local anesthetic ropivacaine was previously demonstrated to attenuate acute rejection after allogeneic lung transplantation in mice. We hypothesized that lung transplantation might result in detectable molecular signs of injury in kidneys and liver and that ropivacaine might attenuate this damage.

Methods

Organs from C57BL/6 mice undergoing allogeneic orthotopic single-lung transplantation were procured at postoperative day 5 and analyzed using Western blot and real-time quantitative polymerase chain reaction probing for Src protein tyrosine kinase, STAT3, and bax/bcl-2. During cold ischemia, the allograft had either been flushed with normal saline only or in combination with ropivacaine (1 µM). A nontransplanted group of animals served as the baseline controls.

Results

The allogeneic stimulus induced by transplantation led to an increase in Src-phosphorylation and STAT3-expression in the kidneys and livers of lung-transplanted mice compared to nontransplanted animals. Bax/bcl-2 as a marker of cellular apoptosis was not affected by the transplantation. In contrast to the findings in the transplanted lungs, the addition of ropivacaine did not have an effect on the examined markers of inflammation in the remote organs.

Conclusions

The observed increase in the inflammatory signaling provides first insight into a possible mechanism, by which remote organ dysfunction after lung transplantation might occur.