Prionas S D, Taylor M A, Fajardo L F, Kelly N I, Nelsen T S, Hahn G M
Cancer Res. 1985 Oct;45(10):4791-7.
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 hepatic toxicity, eight canine liver lobes were exposed to a single 30-min dose of localized hyperthermia in the range of 43.0 degrees C-47.5 degrees C, induced by radiofrequency currents. Four additional liver lobes were conditioned with a pretreatment dose of 43.0 degrees C/30 min and challenged at either 44.5 degrees C/30 min or 47.5 degrees 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.
热疗对肝内或肝周肿瘤的治疗可能会受到正常肝组织热敏感性的限制。为了确定肝毒性与温度的关系,将八个犬肝叶暴露于由射频电流诱导的43.0℃至47.5℃范围内的单次30分钟局部热疗中。另外四个肝叶先接受43.0℃/30分钟的预处理剂量,4小时后再分别接受44.5℃/30分钟或47.5℃/30分钟的激发剂量。使用植入式热电偶传感器测量温度分布。28天后对治疗区域进行取样,并根据组织病理学标准确定肝损伤情况。大多数治疗部位仅表现出轻微改变。与剂量最相关的组织损伤参数为:肝细胞丢失的证据;局灶性纤维化;以及小叶结构扭曲。在几个样本中观察到了坏死区域,但其存在或严重程度与剂量无关。肝包膜、肝小叶、门管区和中央静脉的热损伤未表现出单调的剂量反应关系。数据未显示出热耐受现象;事实上,它们表明(虽未证实)不存在热耐受。如果未产生热耐受,血管效应可能解释这一发现。