Cold preservation injury in organ transplantation: beneficial effects of dopamine and carbon monoxide releasing molecules

Solid organ transplantation, as a treatment modality for patients with end-stage organ disease, has become possible by adequate improvements in surgical techniques, organ preservation and immunosuppression. Static cold preservation is the most widely used modality for preserving cadaveric organs prior to transplantation. However, organ quality and function deteriorate with cold ischemia time. Optimal donor management is therefore of critical importance to the success of transplantation. The studies presented in this thesis were aimed to understand why prolonged cold preservation leads to endothelial cell injury, how this injury subsequently influences vascular function and might provoke inflammation, and finally to find strategies to prevent endothelial damage during static cold storage. With respect to the latter, we focused on two different compounds, i.e. dopamine and related compounds and on carbon monoxide releasing molecules (CORMs). The results of this study show that during prolonged cold preservation important intracellular systems, i.e. redox regulation and calcium homeostasis, are in imbalance. Both dopamine and CORM have the propensity to counteract these changes and hence can maintain tissue quality over a long period of cold preservation. In addition, CORM has an anti-inflammatory potential which might be beneficial to prevent intima hyperplasia, a characteristic hallmark for chronic transplant vasculopathy. This study provides a scientific rational for changing current organ preservation modalities. These changes can be achieved by donor preconditioning or alternatively by supplementation of appropriate additives to the preservation solution, and should as ultimate goal improve transplantation outcome.