Technologies et recherche en matière de transplantation

Induction of Hypometabolism as a Novel Strategy to Minimize Ischemia Reperfusion Injury in Renal Reconstruction Surgeries

Abstract

Bobby Alexander, Meris James, Andrew Fishman, Michael Grasso and Thambi Dorai

Purpose: Hibernation is an altered physiological state which is marked by a characteristic lowering of body temperature and extreme metabolic rate depression. During this period, an animal undergoing hibernation may have its heart rate and blood flow decrease to 1/30 and its oxygen consumption to 1/100 of its respective euthermic levels. Even though these physiological parameters mimic conditions of ischemia their organs particularly their brain, heart, liver and kidneys do not show any detrimental effects of severely reduced blood flow when the animal comes out of hibernation. We wished to explore the benefits of inducing such a hypometabolic state in a mouse ischemiareperfusion injury model.

Methods: We investigated the pre-conditioning effect of administering 5’-Adenosyl Monophosphate (5’-AMP) to mice to create a state of hypometabolism akin to hibernation. This hibernation-like state is used to study its protective effect on a subsequent renal ischemic episode.

Results: Our results strongly suggest that an induction of a hypometabolic state greatly attenuates the ischemic and reperfusion damage to the kidneys, as studied by several specific parameters.

Conclusions: We conclude that reprogramming of the kidney metabolism to a hypometabolic state before ischemia may protect the organ from oxidative damage and reduce ischemia/reperfusion injury. This concept may also be applicable to improve clinical outcomes in renal reconstruction as well as transplantation surgeries.