Hepatic arterial infusion with tumor necrosis factor-α induces early hepatic hyperperfusion

Abstract

Background: Hepatic arterial infusion (HAI) has been developed for high-dose regional chemotherapy of unresectable liver metastases or primary liver malignancies. While it is well known that high concentrations of tumor necrosis factor (TNF)-α damage tumor blood perfusion, there is no information on whether autochthonous liver perfusion is affected by HAI with TNF-α. Therefore, we investigated the effects of HAI with TNF-α on hepatic macro- and microvascular perfusion.

Methods: Swabian Hall pigs were randomized into three groups. HAI was performed with either 20 or 40 µg/kg body weight TNF-α (n = 6 each group). Saline-treated animals served as controls (n = 6). Analyses during a 2-hour post-HAI observation period included systemic hemodynamics, portal venous and hepatic arterial blood flow, portal venous pressure, and the blood flow in the hepatic microcirculation.

Results: HAI with TNF-α caused a slight decrease of mean arterial blood pressure (p < 0.001), which was compensated by a moderate increase of heart rate (p < 0.001). No further systemic side effects of TNF-α were observed. HAI with TNF-α further caused a slight but not significant decrease of portal venous blood flow (p = 0.737) in both experimental groups, paralleled by an increase of hepatic arterial blood flow (p = 0.023, 20 µg/kg; p = 0.034, 40 µg/kg) resulting in an overall hepatic hyperperfusion. The hepatic hyperperfusion after HAI with 20 µg/kg TNF-α was more pronounced and associated with a 40% decrease of the blood flow in the hepatic microcirculation (p = 0.009). HAI with 40 µg/kg TNF-α was only associated with a temporary and moderate total hepatic hyperperfusion and did not affect the blood flow in the hepatic microcirculation.

Conclusion: HAI with TNF-α causes a decrease of portal venous flow; however, this is overcompensated by an increased hepatic arterial blood flow, resulting in a total hepatic hyperperfusion. Moderate total hepatic hyperperfusion does not affect the blood flow in the hepatic microcirculation, while a persistent and more pronounced hyperperfusion may cause hepatic microcirculatory disturbances.