Gillette E L, McChesney S L, Hoopes P J
Int J Radiat Oncol Biol Phys. 1985 Dec;11(12):2091-7. doi: 10.1016/0360-3016(85)90089-6.
Canine hearts were irradiated with a range of total doses given in 2, 3, or 4 Gy per fraction. Echocardiography was done before irradiation and at 3 and 6 months after irradiation. Histologic analyses were done of tissues taken at necropsy 6 months after irradiation. The percentage vascular component in the ventricles decreased with increasing total doses. The connective tissue component increased at lower doses and then decreased at higher doses. There was more fibroblastic proliferation and collagen production in the lower dose range and there may have been more cell killing by the higher doses. There was some evidence of myocardial hypertrophy at higher doses, which would have caused an apparent decrease in the connective tissue component. In either case, surviving fibroblasts would be expected to continue proliferating and producing collagen. At longer time intervals after irradiation the connective tissue component would likely continue to increase as observed clinically. That increase would be proportional to dose, but might not be closely related to initial killing of fibroblasts. Many factors such as changes in blood supply, continued loss of myocardium, and other stresses on the heart could influence the degree of fibrosis at later times. A relationship of response to cell killing appeared to exist based on alpha/beta ratios that were less than 3 Gy whether determined at the mid-range or for the greatest response of vasculoconnective tissues. Alpha/beta ratios ranged from 2.7 to 5 Gy for increases in diastolic wall thickness of the left ventricle at 3 and 6 months after irradiation. The low alpha/beta ratios reflect relatively steep isoeffect curves and have important implications for use of coarser fractionation schedules for treatment volumes that include the heart. The risk of cardiac damage could be significantly increased.
用2、3或4 Gy每分次的一系列总剂量对犬心脏进行照射。在照射前以及照射后3个月和6个月进行超声心动图检查。在照射后6个月尸检时取组织进行组织学分析。心室中血管成分的百分比随总剂量增加而降低。结缔组织成分在较低剂量时增加，然后在较高剂量时降低。在较低剂量范围内有更多的成纤维细胞增殖和胶原蛋白产生，而较高剂量可能有更多的细胞杀伤。在较高剂量时有一些心肌肥大的证据，这会导致结缔组织成分明显减少。在任何一种情况下，存活的成纤维细胞预计会继续增殖并产生胶原蛋白。在照射后的较长时间间隔，结缔组织成分可能会如临床观察到的那样继续增加。这种增加与剂量成正比，但可能与成纤维细胞的初始杀伤没有密切关系。许多因素，如血液供应变化、心肌持续丧失以及心脏上的其他压力，都可能在后期影响纤维化程度。基于α/β比值，无论在中等剂量范围还是血管结缔组织的最大反应时确定，似乎都存在对细胞杀伤的反应关系，α/β比值小于3 Gy。照射后3个月和6个月时，左心室舒张壁厚度增加的α/β比值范围为2.7至5 Gy。低α/β比值反映了相对陡峭的等效效应曲线，对于包括心脏在内的治疗体积使用更粗的分割方案具有重要意义。心脏损伤的风险可能会显著增加。
