Preliminary observation on hepatic arterial infusion under temporary hepatic circulation occlusion in rabbits

Abstract

To explore the advantages, feasibility and limitations of hepatic arterial infusion under temporary hepatic circulation occlusion. Twelve rabbits were randomly divided into two groups: hepatic artery infusion group (HAI group) and hepatic artery infusion under temporary hepatic circulation occlusion group (HAI-THCO). Microcatheters were separately inserted into the proper hepatic artery and right hepatic vein. For the HAI group, 5-Fu (10 mg/ml and 100 mg/kg) was infused into the common hepatic artery with a high pressure injector for 10 minutes. For the HAI-THCO group, the common hepatic artery and hepatic portal vein were temporarily occluded for 15 minutes using artery clamp when 5-Fu was being infused. For the two groups, at 2, 5, 10, 15, 20 and 30 min after the start of infusion, blood samples of the hepatic flow were collected from the right hepatic vein and of the systemic blood flow from the inferior vena cava, 1 ml at each time point. The blood drug concentration of these blood samples was determined by high performance liquid chromatography (HPLC). Except that at 20 and 30 min after infusion, in the HAI group, the blood drug concentration of hepatic circulation was significantly higher than that of systemic circulation (P < 0.05). But in the HAI-THCO group, the blood drug concentration of hepatic circulation was significantly higher than that of systemic circulation at all the time points (P < 0.05). The hepatic circulation blood drug level of the HAI-THCO group was always significantly higher than that of the HAI group (P < 0.05), but the systemic circulation blood drug concentration of the HAI-THCO group was always lower (P < 0.05). The hepatic circulation maximum concentration (Cmax) of blood drug concentration of the HAI-THCO and HAI groups was (23.057±3.270) µg/ml and (4.408±1.092) µg/ml, respectively, and the Cmax of HAI-THCO group was significantly higher (P < 0.001), being 5.23 times of that of HAI group. The systemic circulation Cmax of the two groups was (1.456±0.217) µg/ml and (2.335±0.669) µg/ml, respectively, and the Cmax of HAI group was 1.60 times higher than that of the HAI-THCO group (P = 0.022). The hepatic circulation AUC of HAI-THCO and HAI groups was (368.927±52.416) µg·min·ml(-1) and (65.630±14.928) µg·min·ml(-1), respectively. The AUC of HAI-THCO group was 5.62 times higher than that of the HAI group (P < 0.001). The systemic circulation AUC of the two groups was (27.193±3.948) µg·min·ml(-1) and (45.301±12.275) µg·min·ml(-1), respectively. The AUC of HAI group was 1.67 times higher than that of the HAI-THCO group (P = 0.014). HAI-THCO is a simple and effective regional hepatic infusion chemotherapy technique. It can be performed through occluding the common hepatic artery and the hepatic portal vein by balloon catheter. HAI-THCO can not only increase the blood drug concentration in the hepatic circulation, but also decrease the blood drug concentration in the systemic circulation, therefore, distinctly lowering the systemic toxicity.