Short-Term Effects of N-Acetylcysteine and Ischemic Preconditioning in a Canine Model of Hepatic Ischemia-Reperfusion Injury

Abstract

Aims: We evaluated the possibility that repeated ischemic preconditioning or N-acetylcysteine (NAC) could prevent ischemia-reperfusion injury as determined by indocyanine green plasma disappearance rate (ICG-PDR) or has favorable hemodynamic effects during reperfusion in an in vivo canine liver model. Methods: Under general anesthesia, 3 groups of mongrel dogs (n = 5 per group) were subjected to (1) 60-min hepatic ischemia, (2) same ischemia preceded by intravenous administration of 150 mg kg^–1 NAC, and (3) three episodes of IPC (10-min ischemia followed by 10-min reperfusion) prior to same ischemia. Hepatic reperfusion was maintained for a further 180 min, with hemodynamic and hepatic function parameters monitored throughout. Results: Plasma disappearance rate of indocyanine green and serum levels of aspartate transferase and alanine transferase showed no significant differences between groups. Although liver injury was obvious, reflected by hemodynamic, blood gas, and liver function tests, NAC and IPC failed to prevent decay in hepatic function in this canine model. Conclusion: The results do not support the hypothesis that short-term use of NAC and IPC is beneficial in hepatic surgery.

The Effects of Remote Ischemic Preconditioning and N-Acetylcysteine with Remote Ischemic Preconditioning in Rat Hepatic Ischemia Reperfusion Injury Model

“…Galhardo et al [14] found that 150 mg/kg IV NAC administration to rats before hepatic ischemia, reduced necrosis, apoptosis, and microvesicular steatosis compared to IR group. But controversial to these findings Ghosh et al [30] and Baumann et al [31] could not show the beneficial effects of 150 mg/kg IV NAC before hepatic ischemia.…”

Intravital multiphoton microscopy can model uptake and excretion of fluorescein in hepatic ischemia-reperfusion injury

“…12 I/R injury is a common phenomenon in liver transplantation and resection, with morbidity and mortality as complications. 15,16 During liver transplantation, ischemic damage occurs when blood flow is cut off to the donating liver, and the injury is further intensified when the liver is transplanted into the recipient. 17 The reason for reperfusion injury is the reintroduction of oxygenated blood, which results in oxidative stress, causing increased microvascular permeability, intracellular ATP loss, inflammatory cell infiltration, and, potentially, cell death.…”

Global gene expression profiles of ischemic preconditioning in deceased donor liver transplantation

“…With the continuing shortage of available donor livers, the increased use of extended criteria donor grafts further increases IRI, adversely affecting both short‐term and long‐term outcomes of graft and patient survival 4‐6. Numerous studies have investigated the benefits of pharmacological, heat shock, and ischemic preconditioning (IPC) interventions aimed at decreasing liver IRI 7‐13. Among them, IPC remains the most studied with a nearly uniform protective benefit in animal liver transplantation models with improved survival and decreased IRI 8, 14‐17.…”