The treatment of intrahepatic or perihepatic neoplasms by hyperthermia may be limited by the thermal sensitivity of normal liver tissue. To establish the temperature dependence of hepatictoxicity, eight canine liver lobes were exposed to a single 30-min dose of localized hyperthermia in the range of 43.0°C–47.5°C, induced by radiofrequency currents. Four additional liver lobes were conditioned with a pretreatment dose of 43.0°C/30 min and challenged at either 44.5°C/30 min or 47.5°C/30 min, 4 h later. Temperature distributions were measured using implantable thermocouple sensors. Treated areas were sampled 28 days later, and liver damage was determined using histopathological criteria. Most treated sites showed only modest alterations. The parameters of tissue injury that correlated best with dose were: evidence of hepatocyte loss; focal fibrosis; and distortion of lobular architecture. Areas of necrosis were observed in several samples, but their presence or severity did not correlate with dose. Thermal damage to liver capsule, liver lobules, portal areas, and central veins did not exhibit monotonic dose-response relationships. The data do not demonstrate thermotolerance; in fact, they suggest, although do not prove, its absence. If thermotolerance did not develop, vascular effects might explain such a finding.
Supported in part by USPHS Grants CA 04542, CA 19386, and CA 34686, awarded by the National Cancer Institute, and in part by Veterans Administration Research Funds.