Additives to preservation solutions.

As the impact of ischemia reperfusion injury on graft outcome is now well defined, efforts are made towards decreasing these lesions, typically through the improvement of preservation techniques. The use of pharmacological supplements which could be compatible with any preservation solution used by the transplant center and target specific pathways of IR is an interesting strategy to improve graft quality. However, the extensive number of studies showing the benefits a molecule in an animal model of IR without thorough mechanistic determination of the effects of this agent make it difficult to opt for specific pharmaceutical intervention. Herein we expose studies which demonstrate the benefits of several molecules relying on a thorough mechanical analysis of the events occurring during preservation, both at the cellular and the systemic levels. We believe this approach is the most appropriate to truly understand the potential benefits of a molecule and particularly to design a comprehensive pharmaceutical regiment, with several agents acting synergistically against IR, to improve organ preservation and graft outcome.

Ischemic pre- and post-conditioning: current clinical applications.

Ischemic conditioning is a phenomenon through which short sequences of ischemia-reperfusion applied to an organ confer some degree of protection towards future ischemic insults. This phenomenon was first observed in the mid-1980s in cardiac surgery, and has been since widely studied in different settings. Different sort of ischemic conditioning exist: local vs remote, direct or pharmacological, and with different timeframes of protection. Ischemic conditioning seems especially suited to applications in transplantation since schedules of both cold and warm ischemia, as well as reperfusion, are carefully and easily controlled, and the benefits of protecting fragile organs against ischemia-reperfusion injuries might help widen the pool of possible grafts and ensure better graft function and survival. The pathways through which ischemic conditioning work are many, offering both preservation of cell energy, protection against oxidative stress, better blood flow to organs and protection against apoptosis. In the field of pharmacological conditioning, which tries to mimic the protective effects of traditional ischemic conditioning without the potential side-effects associated with vessel clamping, many common-use drugs including anesthetics have been shown to be effective. Significant results have been obtained in small animal models, but while ischemic conditioning is successfully used in cardiac surgery, studies in large animal models and human applications in liver and kidney transplantation are still inconclusive.