Experimental Brain Death Models in Liver Transplantation

Abstract

Most organs for transplantation are currently procured from brain-dead donors; however, brain death is an important risk factor in liver transplantation. In addition, to counteract the shortage of liver grafts, transplant centers accept the use of sub-optimal livers, which may show higher risk of primary non-function or initial poor function. Very few literatures exist regarding liver transplantation using brain-dead donors, or about brain death and its effects on sub-optimal grafts in such surgical situation. This chapter aims to describe the pathophysiological changes occurring in liver grafts during brain death and focuses on the strengths and limitations of experimental models used to study the effect of brain death on optimal and sub-optimal (specially steatotic) liver grafts. Depending on the use of experimental models that simulate as much as possible the surgical conditions present in clinical practice, therapeutic strategies designed in animal models could be more successfully translated to the bedside.

New Perspectives on the Use of Sub-Optimal Donor Livers

“…A shortage of donor organs remains a major obstacle to the widespread application of LT in patients with end-stage liver disease [73,74]. This shortage could be alleviated by routine use of sub-optimal donor livers including those from donors with viral infections, although infection of the graft is almost universal and can lead to chronic hepatitis, cirrhosis, and graft failure.…”

Hepatic Regeneration Under Warm or Cold Ischemia Conditions: Controversies and New Approaches

“…The results of animal studies can be extrapolated to human beings, even though there are limitations such as the differences in ischemia tolerance, the anatomy of the organ in different species, and differences in the surgical conditions applied in clinical practice and in experimental models [21]. Therefore, the correct choice of animal species and experimental model, and the standardization of the protocol according to the clinical issue under study, is particularly important [14].…”

“…Small animals like rats and mice are exceptionally useful because they are easy to handle, present minimal, financial, logistical or ethical problems, and allow genetic alterations such as the creation of transgenic and knock-out animals [14]. Larger animals (pigs, sheep, and dogs) have a more similar anatomy and physiology to humans, but their use is restricted by serious financial and logistical difficulties, ethical concerns, and the limited availability of immunological tools for use in these species [14,21]. The age and sex of animals are also issues to consider.…”