Gillette S M, Gillette E L, Shida T, Boon J, Miller C W, Powers B E
Department of Radiological Health Sciences, Colorado State University, Fort Collins 80523.
Radiother Oncol. 1992 Jan;23(1):41-52. doi: 10.1016/0167-8140(92)90304-d.
The mediastinal tissues which included heart, lung, trachea and esophagus of 70 adult beagle dogs were irradiated to a range of total radiation doses between 24 and 68 Gy given in 2, 3 and 4 Gy fractions. The purpose of the study was the calculation of alpha/beta ratios for morphologic and functional changes of the mediastinal tissues. Functional assays including echocardiography, electrocardiography, right heart hemodynamics and cardiac output were performed. Histomorphometric analyses of all tissues included in the field were done 2 years after treatment. Euthanasia was performed on 7 of 70 dogs prior to 2 years due to congestive heart failure and seven other dogs had signs of heart failure 2 years after treatment. Heart failure was thought to be caused by either pericardial effusions or constrictive pericarditis in these dogs. Heart failure occurred at doses of 62 and 68 Gy given in 2 Gy fractions, 60 Gy given in 3 Gy fractions and 52 Gy given in 4 Gy fractions. The ED50 values for pericardial fibrosis for 2, 3 and 4 Gy fractions were 46.1, 43.9 and 26.6 Gy, respectively. An alpha/beta ratio of 2.5 Gy was calculated by direct quantal response analysis. Small foci of myocytolytic lesions were detected in 11 dogs. Calculated ED50 values for myocytolysis were 70.4 Gy given in 2 Gy fractions and 50.8 Gy given in 4 Gy fractions. The estimated alpha/beta ratio was 3.2 Gy. Heart rates determined from physical examination and frequency of S-T segment changes increased with increasing dose. No other dose related changes were found in any of the other functional parameters. Functional changes were detected in the 14 dogs with clinical signs of heart failure. Focal consolidation and subpleural fibrosis were present in the irradiated lung volume. These late changes had no detectable physiologic effect in these dogs because of the small volume of lung irradiated. The ED50 values for lung consolidation were 54.3, 45.8 and 26.6 Gy after 2, 3 or 4 Gy fractions, respectively. The estimated alpha/beta ratio was 3.4 Gy. No dose-related changes could be detected in the trachea or esophagus at 2 years after treatment. These results demonstrate that lung and pericardium are the most responsive tissues in the mediastinum within the first 2 years after treatment. Myocardial lesions were present with high ED50 values, but were not found to be functionally significant at 2 years after irradiation. Human clinical data indicate that longer observation periods are needed for development of these lesions.(ABSTRACT TRUNCATED AT 400 WORDS)
对70只成年比格犬的纵隔组织（包括心脏、肺、气管和食管）进行照射，总辐射剂量范围为24至68 Gy，分2、3和4 Gy分次给予。本研究的目的是计算纵隔组织形态学和功能变化的α/β比值。进行了包括超声心动图、心电图、右心血流动力学和心输出量在内的功能测定。治疗2年后对照射野内所有组织进行组织形态计量学分析。70只犬中有7只因充血性心力衰竭在2年之前实施了安乐死，另外7只犬在治疗2年后出现心力衰竭迹象。这些犬的心力衰竭被认为是由心包积液或缩窄性心包炎引起的。心力衰竭发生在以2 Gy分次给予62和68 Gy剂量时，以3 Gy分次给予60 Gy剂量时，以及以4 Gy分次给予52 Gy剂量时。2、3和4 Gy分次照射下心包纤维化的ED50值分别为46.1、43.9和26.6 Gy。通过直接定量反应分析计算出α/β比值为2.5 Gy。在11只犬中检测到小灶性肌溶解病变。计算出的2 Gy分次照射下肌溶解的ED50值为70.4 Gy，4 Gy分次照射下为50.8 Gy。估计的α/β比值为3.2 Gy。根据体格检查确定的心率和S - T段改变频率随剂量增加而升高。在任何其他功能参数中未发现与剂量相关的其他变化。在14只有心力衰竭临床体征的犬中检测到功能变化。照射的肺容积中存在局灶性实变和胸膜下纤维化。由于照射的肺容积小，这些晚期变化在这些犬中未检测到可察觉的生理效应。2、3或4 Gy分次照射后肺实变的ED50值分别为54.3、45.8和26.6 Gy。估计的α/β比值为3.4 Gy。治疗2年后在气管或食管中未检测到与剂量相关的变化。这些结果表明，在治疗后的前2年，肺和心包是纵隔中反应最敏感的组织。心肌病变具有较高的ED50值，但在照射后2年未发现其具有功能意义。人类临床数据表明，这些病变的发展需要更长的观察期。（摘要截断于400字）
