Direct, remote and combined ischemic conditioning in liver surgery

Abstract

Liver ischemia-reperfusion injury is a major cause of postoperative liver dysfunction, morbidity and mortality following liver resection and transplantation. Ischemic conditioning has been shown to ameliorate ischemia-reperfusion injury in small animal models. It can be applied directly or remotely when cycles of ischemia and reperfusion are applied to a distant site or organ. Considering timing of the procedure, different protocols are available. Ischemic preconditioning refers to that performed before the duration of ischemia of the target organ. Ischemic perconditioning is performed over the duration of ischemia of the target organ. Ischemic postconditioning applies brief episodes of ischemia at the onset of reperfusion following a prolonged ischemia. Animal studies pointed towards suppressing cytokine release, enhancing the production of hepatoprotective adenosine and reducing liver apoptotic response as the potential mechanisms responsible for the protective effect of direct tissue conditioning. Interactions between neural, humoral and systemic pathways all lead to the protective effect of remote ischemic preconditioning. Despite promising animal studies, none of the aforementioned protocols proved to be clinically effective in liver surgery with the exception of morbidity reduction in cirrhotic patients undergoing liver resection. Further human clinical trials with application of novel conditioning protocols and combination of methods are warranted before implementation of ischemic conditioning in day-to-day clinical practice.

Effects of remote ischemic preconditioning in hepatectomy: a systematic review and meta-analysis

“…The use of the Pringle maneuver during hepatectomies is highly likely to cause HIRI [ 5 ]. Therefore, a subgroup analysis was performed to determine whether the Pringle maneuver should be used routinely.…”

“…During liver resections, intermittent portal vein triple clamping (Pringle maneuver) is associated with controlled low central venous pressure, which reduces intraoperative blood loss [ 2 , 4 ]. However, subsequent tissue ischemia and reperfusion may lead to hepatic ischemia-reperfusion injuries (HIRIs), which usually occur when blood supply to the liver is temporarily blocked and subsequently restored [ 5 ].…”

“…After an extensive hepatectomy, HIRI of the residual liver may be a serious complication, leading to postoperative liver dysfunction and increased mortality [ 5 ]. In order to protect the residual liver from HIRI, several techniques have been used, including drugs and ischemic preconditioning, or remote ischemic preconditioning (RIPC), none of which are established as standard of care.…”

“…In order to protect the residual liver from HIRI, several techniques have been used, including drugs and ischemic preconditioning, or remote ischemic preconditioning (RIPC), none of which are established as standard of care. Organ protection by RIPC began with the study of cardiac muscle protection, which involves repeated temporary cessation of blood flow to the limbs [ 5 , 8 ]. RIPC procedures are non-invasive and therefore a more suitable method to reduce HIRI.…”

NGAL in the Development of Acute Kidney Injury in a Murine Model of Remote Ischaemic Preconditioning and Liver Ischaemia Reperfusion

“…Evidence from a variety of different experimental and clinical settings suggests that this approach can reduce the systemic inflammatory response and downregulate IR injury [13][14][15][16][17][18]. The underlying mechanisms of protection remain poorly understood but involve neural, humoral and systemic pathways and include a downregulation of oxidative stress and upregulation of protective pathways within the transplant organ [19]. Whilst experimental animal models have provided promising results, there has been limited translation into clinical practice [20][21][22][23][24].…”