The effect of Lazaroid U-74389G on extended liver resection with ischemia in dogs

Surgery. 1999 Nov;126(5):908-17.

Abstract

Background: In liver surgery, total clamping of the portal triad (Pringle's procedure) is commonly used, and it sometimes causes liver failure. This study was designed to evaluate the effect of Lazaroid U-74389G (LAZ-G), which inhibits iron-dependent lipid peroxidation, on ischemia-reperfusion injury during liver resection in dogs.

Methods: The experiment animals were divided into 2 groups. The control group was subjected to 60 minutes of warm ischemia by partial inflow occlusion. The LAZ-G-treated group received LAZ-G before ischemia and then underwent liver ischemia. After reperfusion, the nonischemic lobes were resected, and the remnant liver function was evaluated.

Results: The LAZ-G-treated group showed a significantly improved animal survival rate. Biochemical analysis and morphologic evaluation by electron microscopy suggest that LAZ-G pretreatment protects both hepatic parenchymal cells and sinusoidal endothelial cells from ischemia-reperfusion injury. Expression of IL-1 beta messenger RNA in hepatic venous blood was measured by a reverse transcriptase-polymerase chain reaction; it was shown to be inhibited in the LAZ-G-treated group after reperfusion. This suggests that LAZ-G decreases the activation of proinflammatory cytokine expression.

Conclusions: Lazaroid U-74389G ameliorates ischemia-reperfusion injury caused by Pringle's procedure during extensive liver resection. This agent may therefore be clinically applicable for extended liver surgery involving vascular isolation.

MeSH terms

  • Animals
  • Dogs
  • Female
  • Hepatectomy* / adverse effects
  • Hepatectomy* / methods
  • Hepatic Veins
  • Immunosuppressive Agents / therapeutic use*
  • Interleukin-1 / genetics
  • Ischemia / prevention & control*
  • Liver / blood supply*
  • Liver / enzymology
  • Liver / metabolism
  • Liver / pathology
  • Liver Failure / prevention & control
  • Male
  • Pregnatrienes / therapeutic use*
  • RNA, Messenger / blood
  • Reperfusion Injury / prevention & control

Substances

  • Immunosuppressive Agents
  • Interleukin-1
  • Pregnatrienes
  • RNA, Messenger
  • U 74389F