Protective Effect of Ischemic Preconditioning on Liver Preservation-Reperfusion Injury in Rats

Abstract

The current results show that ischemic preconditioning protects the liver graft from subsequent long-term cold preservation-reperfusion injury in a rat liver transplantation model. The protective role of ischemic preconditioning may be mediated by the endogenous production of NO.

Ischemic preconditioning of the liver: A few perspectives from the bench to bedside translation

“…2,[30][31][32][33] We examine the available evidence and attempt to provide some potential reasons for this disparity.…”

“…The merits of this composite endpoint were discussed in the Severity of Ischemia and RP Injury section, subsection Liver Transplantation. Remote preconditioning via limb ischemia 81,82 (1) Applicable to DCD donors; (2) Inexpensive Hypertonic saline dextran 83,84 (1) Volume enhancement, especially in donors and applicable to DCD donors; (2) Inexpensive Anesthetic preconditioning (volatile anesthetics, nitric oxide) 3,4,85 (1) May not be feasible in all donor hospitals; (2) Nitric oxide is expensive Pharmacologic preconditioning (nitrites, adenosine, interleukin-10) 2,6,7 (1) More expensive; (2) Potential side effects of agents NOTE: In contradistinction to ischemic preconditioning, all listed modalities are applicable in both liver donors and recipients. They share avoidance of direct organ ischemia and, when used in deceased donors, have the potential to benefit recipients of many organs.…”

“…Preconditioning strategies effective in the laboratory include ischemic preconditioning (IPC), anesthetic preconditioning, hyperthermic or heat-shock preconditioning, and pharmacological preconditioning. [1][2][3][4][5][6][7] In the past decade, serious efforts have commenced to translate some of the robust benefits of preconditioning against ischemia reperfusion (RP) to the clinical arena. Although all of the preconditioning methods offer potential clinical benefits, much of the initial translational effort has focused on IPC, probably due to its extensive and consistently beneficial laboratory experience.…”

“…[10][11][12][13][14][15] In laboratory animals and humans, IPC of the liver may be induced either by a single short period of ischemia or multiple short cycles of ischemia (or intermittent hilar clamping). 16 In a rat liver transplant model, Yin et al 2 investigated single IPC periods ranging between 5 and 20 minutes and showed that 10 minutes induced the best protection. Although 10 to 15 minutes of RP after the preconditioning ischemia has become a methodological tradition following the initial laboratory work, more recent work by Glanemann et al, 17 in rat liver warm ischemia, showed that 30 to 45 minutes of RP were more effective than 5 to 15 minutes.…”

Microvascular dysfunction induced by reperfusion injury and protective effect of ischemic preconditioning

“…Preconditioning also appears to be a useful strategy against the deleterious effects of cold storage-reperfusion injury, since it was observed that ischemic-preconditioned grafts had reduced levels of transaminases and TNF-␣, as well as augmented bile flow and improved tissue blood flow [92][93][94]. Accordingly, in a recent publication it was observed that preconditioned rat livers were more tolerant against cold-storage-reperfusion injury, most probably due to a decreased production of O 2 Ϫ• by Kupffer cells.…”