Hyperthermic isolation-perfusionin vivo of the canine liver

Abstract

Regional hyperthermia (42°) was applied to the canine liver by isolation‐perfusion in order to demonstrate that dog survival and maintenance of hepatic functional integrity were possible. Flow to the liver, 1 ml/min/g, was provided by gravity to the portal vein at 2/3 total flow, and by pump to the hepatic artery at 1/3 total flow. After 1 hour perfusion at 37°, 4/6 dogs survived and 5/8 survived perfusion at 42°. Hypoglycemia contributed to the two deaths at 37° and one at 42°. After two‐hour perfusion at 37°, 5/5 dogs survived, and 3/5 survived at 42°. After four‐hour perfusion at 37°, 1/1 dog survived, and 1/1 survived at 42°. Hyperlactemia occurred during all perfusions, but plateaued at a level of 8–10 mM. Plasma SGPT, SGOT, or 5‐nucleotidase levels during and after perfusion were mildly elevated, but returned to normal within 4–7 days. Perfusate chemistries (lactate, pyruvate, glucose, urea, total amino acids, ketone bodies, and enzymes) were used as indicators of hepatic functional integrity. Lactate in the perfusate showed no significant differences (P < 0.05) between 37 and 42°. Glucose increased in the perfusate during all perfusions. Urea synthesis occurred during all perfusions and was unchanged by a temperature of 42°. The total amino acid levels in the perfusate reflected endogenous proteolysis, which was unchanged at 42°. Ketone body production was increased during the two‐hour perfusions due to the addition of Intralipid to the perfusate. There were no significant differences in the perfusate enzyme levels at 37 and 42°. The data presented indicate that hepatic functional integrity can be maintained in the canine liver during isolation‐perfusion at 42°. Support of the dog during and after the temporary anhepatic state may be the crucial factor to survival. Thermotherapy by isolation‐perfusion of the liver could be useful for treating patients with cancer limited to the liver.

Isolated hepatic perfusion in the pig with TNF-alpha with and without melphalan

“…This suggests that the mild hepatotoxic phenomena observed were primarily caused by the IHP procedure itself and that the addition of the drugs used, in particular rhTNF-a, does not lead to additional hepatotoxicity. These findings are in agreement with those reported on IHP with hyperthermia and/or standard chemotherapeutics (Skibba, 1983(Skibba, , 1988Sindelar, 1985;Van de Velde, 1986;Aigner, 1988;Hafstrom 1994).…”

“…Indeed, Boddie et al (1979) performed IHP solely via the PV and demonstrated significant hepatic damage. In accordance with most other reports on IHP, we have not been able to confirm these findings (Skibba, 1983(Skibba, , 1988Sindelar, 1985;Van de Velde, 1986;Aigner, 1988;Hafstrom, 1994).…”

“…Indeed, Boddie et al (1979) performed IHP solely via the PV and demonstrated significant hepatic damage. In accordance with most other reports on IHP, we have not been able to confirm these findings (Skibba, 1983(Skibba, , 1988Sindelar, 1985;Van de Velde, 1986;Aigner, 1988;Hafstrom, 1994).At present, it is unknown which drug, or combination of drugs, would provide antitumoral efficacy in the IHP setting. TNF-x with and without melphalan was selected for this study based on its clinical success (100% limb salvage and a 90% overall response) in isolated limb perfusions for irresectable melanoma and sarcoma .…”

“…Several techniques have been developed for regional therapy of hepatic malignancies, of which hepatic artery infusion (HAI) has become most widely used (Sullivan, 1964;Pentecost, 1993;De Takats, 1994 (Kemeny, 1987;Pentecost, 1993;De Takats, 1994;Chang, 1987). Alternatively, isolated hepatic perfusion (IHP), including total vascular isolation of the liver, has been reported to significantly increase intrahepatic drug concentrations when compared with HAI, while maintaining sufficiently low systemic drug levels (Aigner, 1982;Skibba, 1983;De Brauw, 1988;Marinelli, 1991;Radnell, 1990). However, large animal studies have revealed systemic leakage of the perfused anti-tumour agent owing to incomplete vascular isolation in up to 20% of animals (Sindelar, 1985;Van de Velde, 1986).…”

Interstitial Laser Hyperthermia for the Treatment of Hepatic and Pancreatic Tumours

“…Healing of the heated areas was seen. Hyperthermia of the whole liver caused some necrosis, more in that of the canine (Skibba and Condon, 1985) than the rat (Skibba and Collins, 1978;Miyazaki, 1983), with a 25% mortality in the former. Liver blood flow is reduced by hyperthermia as is that of innoculated liver tumours (Hugander et al, 1983) that undergo necrosis.…”