Reduced hepatic arterial perfusion impairs the recovery from focal hepatic venous outflow obstruction in liver-resected rats.

Abstract

Extended partial hepatectomy (PH) in patients is leading to portal hyperperfusion but reduced hepatic arterial perfusion (HAP), and is invariably causing focal hepatic venous outflow obstruction (FHVOO). We observed in a rat model that PH in combination with right median hepatic vein ligation (RMHV-L) caused confluent parenchymal necrosis interspersed with viable portal tracts in the obstructed territory and large sinusoidal vascular canals in the border zone. Lack of HAP impaired the spontaneous course of recovery in terms of enlarged parenchymal necrosis, delayed regeneration, and the absence of draining vascular canals. We aimed to investigate whether pharmacological intervention modulates the imbalance between portal venous and hepatic arterial inflow, aggravates the liver damage, and delays the recovery process after FHVOO in liver-resected rats. Male Lewis rats were subjected to 70% PH and RMHV-L. Molsidomine or NG-nitro-L-arginine methyl ester (L-NAME) or saline were applied daily. Hepatic damage, microcirculation, regeneration, and vascular remodeling were evaluated at postoperative days 1, 2, and 7. Animals subjected to RMHV-L only were used as "no HAP" control. Significant increase of portal venous inflow with a concomitant decrease in HAP was observed in all groups after PH. Molsidomine treatment did neither affect hepatic hemodynamics nor the spontaneous recovery. In contrast, L-NAME treatment further decreased HAP which impaired hepatic microcirculation, aggravated parenchymal damage, decelerated recovery, and impaired the formation of sinusoidal canals. Reduction of HAP through inhibition of nitric oxide production worsened the recovery from FHVOO. Drugs increasing HAP need to be evaluated to reverse the hyperperfusion-induced impairment of the spontaneous course after FHVOO.