Intracellular oxygenation and cytochrome oxidase C activity in ischemic preconditioning of steatotic rabbit liver.

BACKGROUND: Mild to moderate steatotic livers are used as marginal donors in liver transplantation. Very little is known about the mechanisms of ischemia reperfusion (IR) injury (IRI) in fatty liver. This study aimed to establish whether cytochrome oxidase C (COX) activity is compromised by IRI in fatty liver and whether ischemic preconditioning (IPC) can protect COX activity. METHODS: New Zealand rabbits were fed on a high-cholesterol diet for 8 weeks to induce moderate hepatic steatosis. Three groups were tested. The IR group underwent 60 minutes of ischemia, followed by 7 hours of reperfusion. The IPC group (IPC + IR) underwent 5 minutes of ischemia, followed by 10 minutes of reperfusion and then 60 minutes of ischemia and 7 hours of reperfusion. The control group (sham) underwent the same surgical procedure, but ischemia was not induced. Deoxyhemoglobin, oxyhemoglobin, and change in the redox state of COX was continuously monitored in vivo by near-infrared spectroscopy. COX and citrate synthase (CS) activity assays were carried out on liver biopsy specimens in vitro. Bile was collected continuously during the procedure and analyzed using proton nuclear magnetic resonance spectroscopy. RESULTS: The IR group had decreased COX activity and tissue oxygenation represented by deoxyhemoglobin, oxyhemoglobin, COX, and elevated redox ratios of lactate/pyruvate and ß-hydroxybutarate/acetoacetate in vivo and a decrease in COX and CS activity in vitro. The IPC + IR group showed higher levels of all measured parameters in vivo and showed a smaller decrease in COX and CS activity in vitro. CONCLUSION: This study shows that IRI affects COX activity in fatty livers. This is attenuated by IPC.

Acute limb ischemia caused by femoral arterial line induces remote liver injury in a rabbit model of liver ischemia/reperfusion injury.

Femoral arterial lines are used for continuous monitoring of arterial blood pressure in experimental studies. However, placement of a catheter in the femoral artery could produce acute limb ischemia with associated systemic effects. The aim of this study was to investigate the effect of femoral arterial line insertion on liver function, in a rabbit liver lobar ischemia-reperfusion (I/R) model. Four groups of animals (n = 6 each) were studied: groups 1 and 2 (sham) underwent laparotomy but no liver ischemia. In groups 3 and 4 (I/R), liver lobar ischemia was induced for 60 minutes followed by 7 hours of reperfusion. In groups 1 and 3, the arterial line was placed in the femoral artery whereas in groups 2 and 4 in the ear artery. Liver function was assessed by serum alanine aminotransferase (ALT) activity, bile flow, plasma lactate levels, and histology. Results are expressed as mean +/- SEM. Alanine aminotransferase activity and lactate levels were significantly higher in the I/R femoral line group compared with the I/R ear line group at 7 hours postreperfusion. Bile production was significantly lower (75 +/- 9.6 vs 112 +/- 10 microL/min per 100 g liver weight). Histopathology showed more extensive hepatocellular necrosis and neutrophil accumulation in the I/R femoral line group compared with I/R ear line group. The sham femoral group showed liver injury, which was more marked than the ear line group (all P < .05). In conclusion, femoral artery cannulation induces remote liver injury. The use of femoral arterial lines should be avoided in experimental studies concerning liver function.