Van Vleet J F, Ferrans V J, Badylak S F
Am J Vet Res. 1982 Dec;43(12):2173-82.
Chronic doxorubicin (adriamycin; ADR) intoxication was produced in Beagle dogs by weekly IV injections (1 mg/kg of body weight) for 20 weeks (cumulative dose 400 mg of ADR/m2). Group A (5 dogs) were given ADR only; group B (5 dogs), ADR and daily supplements of 0.5 mg of L-thyroxine (T4) (twice the recommended maintenance dose); and group C (5 dogs), ADR and 2.0 mg of T4 daily (8 times the recommended maintenance dose). The control group D (5 dogs) was given 0.5 mg of T4 daily. The ADR-induced cutaneous lesions (alopecia and melanosis), body weight loss, hematologic alterations, and myocardial microscopic and ultrastructural alterations (sarcoplasmic vacuolation and myocytolysis) were present with equal severity in the 3 ADR-treated groups, with or without T4 supplements. Six of the 15 ADR-treated dogs died during the study: 3 dogs had pneumonia, 1 dog had no established cause of death, and 2 dogs (from group C) had lesions of congestive cardiac failure. All ADR-treated dogs given a cumulative dose of 340 mg of ADR/m2 or more had characteristic myocardial histopathologic alterations, but 2 dogs that died after they were given only 140 or 260 mg of ADR/m2 had no microscopic evidence of myocardial damage. Low serum triiodothyronine (T3) concentrations were present in ADR-treated dogs after 28, 56, 84, 112, and 140 days and were attributed to faulty extrathyroidal conversion of T4 to T3. Serum T4 concentrations were high in dogs given 2 mg of T4/day (group C) after 28, 56, 84, and 112 days, but were low terminally as those dogs became debilitated from chronic ADR toxicosis. Unusual clinical signs or cardiac alterations of hyperthyroidism did not develop in the dogs given T4 supplements (groups B, C, and D). Our findings indicate that supplements of T4 do not alter the development of the cardiac and extracardiac lesions of chronic ADR toxicosis in dogs and indicate that the ADR-induced lesions probably are not mediated via hypothyroidism.
通过每周静脉注射（1毫克/千克体重）持续20周（阿霉素累积剂量为400毫克/平方米），在比格犬中造成慢性阿霉素中毒。A组（5只犬）仅给予阿霉素；B组（5只犬）给予阿霉素并每日补充0.5毫克左旋甲状腺素（T4）（为推荐维持剂量的两倍）；C组（5只犬）给予阿霉素并每日补充2.0毫克T4（为推荐维持剂量的8倍）。对照组D组（5只犬）每日给予0.5毫克T4。在3个接受阿霉素治疗的组中，无论是否补充T4，阿霉素诱导的皮肤病变（脱发和黑变病）、体重减轻、血液学改变以及心肌微观和超微结构改变（肌浆空泡化和心肌细胞溶解）的严重程度相同。在研究过程中，15只接受阿霉素治疗的犬中有6只死亡：3只犬患肺炎，1只犬死因不明，2只犬（来自C组）有充血性心力衰竭病变。所有累积剂量达到或超过340毫克阿霉素/平方米的接受阿霉素治疗的犬都有典型的心肌组织病理学改变，但有2只犬在仅接受140或260毫克阿霉素/平方米后死亡，心肌没有微观损伤证据。在接受阿霉素治疗的犬中，在第28、56、84、112和140天后出现低血清三碘甲状腺原氨酸（T3）浓度，这归因于T4向T3的外周甲状腺转化异常。在每日给予2毫克T4的犬（C组）中，在第28、56、84和112天后血清T4浓度较高，但在这些犬因慢性阿霉素中毒而衰弱时，最终血清T4浓度较低。在补充T4的犬（B组、C组和D组）中未出现甲状腺功能亢进的异常临床体征或心脏改变。我们的研究结果表明，补充T4不会改变犬慢性阿霉素中毒的心脏和心脏外病变的发展，表明阿霉素诱导的病变可能不是通过甲状腺功能减退介导的。
