Beyond Preconditioning: Postconditioning as an Alternative Technique in the Prevention of Liver Ischemia‐Reperfusion Injury

Abstract

Liver ischemia/reperfusion injury may significantly compromise hepatic postoperative function. Various hepatoprotective methods have been improvised, aiming at attenuating IR injury. With ischemic preconditioning (IPC), the liver is conditioned with a brief ischemic period followed by reperfusion, prior to sustained ischemia. Ischemic postconditioning (IPostC), consisting of intermittent sequential interruptions of blood flow in the early phase of reperfusion, seems to be a more feasible alternative than IPC, since the onset of reperfusion is more predictable. Regarding the potential mechanisms involved, it has been postulated that the slow intermittent oxygenation through controlled reperfusion decreases the burst production of oxygen free radicals, increases antioxidant activity, suppresses neutrophil accumulation, and modulates the apoptotic cascade. Additionally, favorable effects on mitochondrial ultrastructure and function, and upregulation of the cytoprotective properties of nitric oxide, leading to preservation of sinusoidal structure and maintenance of blood flow through the hepatic circulation could also underlie the protection afforded by postconditioning. Clinical studies are required to show whether biochemical and histological improvements afforded by the reperfusion/reocclusion cycles of postconditioning during early reperfusion can be translated to a substantial clinical benefit in liver resection and transplantation settings or to highlight more aspects of its molecular mechanisms.

Novel Targets for Treating Ischemia-Reperfusion Injury in the Liver

“…In addition, the ischemic preconditioning is carried out prior to surgery, and is limited for treating acute liver injuries. The difficulty in properly determining the time and number of reperfusion/reocclusion cycles limits the clinical use of ischemic preconditioning [ 19 ]. In the stage of ischemia, the organ should be kept in a cold storage condition to reduce metabolism and organ dysfunction.…”

Liver ischemia and reperfusion injury. Pathophysiology and new horizons in preconditioning and therapy

“…The associations of the two processes presented synergistic action in comparison with PCI or isolated PosCI. ALT and AST decrease while antioxidant activity, hypoxia tolerance and cell proliferation increase; however, regarding the release of cytokines, there was no difference about the conditions alone 34 .…”

Intrathecal morphine pretreatment ameliorated hepatic ischemia-reperfusion injury by reducing inflammation through peripheral and spinal opioid activation in rats

“…When blood reflows after a long interruption, recruited neutrophils aggressive hepatocytes directly. Numerous methods are reported to attenuate hepatic IRI including ischemic pretreatment, ischemic postconditioning and medication pretreatment [4][5][6][7]. To treat all patients in clinics and set up more efficient therapeutic methods, more clinical studies are required Neural axis analgesia is a common technique used for patients undergoing abdominal surgery [8].…”