Exogenous L-Arginine Protects Liver Microcirculation from Ischemia Reperfusion Injury

Abstract

Hepatic ischemia followed by reperfusion evokes an imbalance between the vasoregulatory compounds endothelin and nitric oxide (NO) followed by constriction of the vascular bed, leading to microcirculatory disturbances and reduced blood flow, thereby causing hypoxia and liver damage. The aim of this study was to protect the liver microcirculation by maintaining this delicate balance. Material and Methods: In an in vivo ischemia/reperfusion model with portal decompression by a splenocaval shunt, hepatic ischemia was induced for 30 min by Pringle’s maneuver. The effect of the NO donor L-arginine (400 mg/kg b.w. i.v.) was assessed by in vivo microscopy. Microhemodynamic studies, including the sinusoidal perfusion rate, diameters of hepatic sinusoids and postsinusoidal venules, leukocyte endothelium interactions and leukocyte velocity were performed. Microcirculatory data were compared with local tissue pO₂ and serum transaminase levels. Results: After ischemia the diameters of sinusoids and postsinusoidal venules were significantly reduced to 76 ± 7 and 86 ± 10% respectively in the nontreatment group, but dilated to 102 ± 3 and 105 ± 7% in the group treated with L-arginine (p < 0.001). The percentage of permanently adherent leukocytes in sinusoids and venules was increased by ischemia, but L-arginine reversed this increase (p < 0.001). Perfusion rate was improved to 90 ± 2 compared with 83 ± 5% in the untreated group (p < 0.01). Systemic arterial blood pressure was not affected by administration of the NO donor. The postischemic increase in serum transaminase levels was diminished in the treatment group (ASAT: p < 0.05). Local postischemic hepatic tissue pO₂ was significantly decreased to 45% of basal values after 30 min and to 55% after 60 min of reperfusion (p < 0.05). Administration of L-arginine results in a significant increase in local tissue pO₂ to 86 and 106% of basal values respectively (p < 0.05). Conclusion: These data indicate that L-arginine improves hepatic microcirculation after warm ischemia by increasing sinusoidal perfusion rate and by diminishing leukocyte endothelium interactions. Maintained integrity of microcirculation is associated with sufficient oxygen supply and improved hepatocellular function.