Effects of systemic hyperthermia and intrahepatic infusion with 5-fluorouracil

Abstract

Potential hepatotoxicity from systemic hyperthermia (43°C) ± simultaneous hepatic artery infusion with 5-FU was evaluated in an animal model. Twenty-two dogs had aorta-vena caval shunts (8 mm Dacron grafts) placed, and 10 of these dogs had silastic catheters inserted in their hepatic arteries. Two weeks later, Group I (n = 8) was heated to 43°C for one hour (distal esophageal + intrahepatic temperature) using the shunts and blood-heat exchangers; Group II (n = 6) was heated to 43°C for one hour with simultaneous intrahepatic infusion of 5-FU (10 mg/kg); Group III (n = 8) was shamheated (37°C) and underwent a one hour intrahepatic infusion with 5-FU (10 mg/kg). Serum alkaline phosphatase, SGOT, SPGT (IU/ml) and bilirubin were measured, and liver biopsies were obtained at 0 and 1 hour, at one and seven days. Mean SGOT levels increased significantly (P < 0.05) in Group II from 19 ± 2 to 31 ± 6 and 63 ± 18 at one hour and one day; these levels rose slightly in Group I from 31 ± 5 to 40 ± 8 and 47 ± 8 at one hour and one day. Hepatocellular enzyme levels returned to normal at seven days in both groups. Mean SGOT and SGPT levels remained similar in Group III at all time periods. No significant differences in mean serum alkaline phosphatase or bilirubin levels were noted. There was no histologic evidence of hepatocellular necrosis at any time period. Survival was 6/8, 5/6 and 8/8 dogs in Groups I, II, and III, respectively. Systemic hyperthermia to 43°C for one hour in dogs does not adversely affect serum hepatic enzymes or cell structure; reversible serum hepatic enzyme changes occurred when hyperthermia was combined with hepatic artery infusion with 5-FU.