Doxorubicin-related effects on cardiorespiratory function and body composition.
Doxorubicin-related effects on cardiorespiratory function and body composition.
复制标题
阿霉素对心肺功能和身体成分的相关影响。
DOI：
10.1016/j.ahjo.2024.100360
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Smuder,AshleyJ
中科院分区：
文献类型：
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作者：
Smuder,AshleyJ
阿霉素(DOX)是一种高效的化疗药物，用于治疗许多实体瘤、血液和妇科肿瘤。然而，它的使用与急性和慢性不良心血管事件有关，这些事件对癌症患者的生活质量和长期生存产生负面影响[1]。虽然啮齿动物和人类在心血管方面存在差异，主要与不同物种之间心率的巨大差异有关，但利用小型啮齿动物来模拟人类疾病有明显的优势[2]。在DOX化学毒性的情况下，评估心脏损伤、心肺容量和身体成分的能力使得急性和慢性DOX毒性啮齿动物模型的翻译潜力得到改善，同时也允许在分子水平上进行研究[1]。此外，这些研究需要较少的药物和较短的时间，从而提高了了解DOX心脏毒性机制和测试潜在治疗对策的效率[3]。利用一个大鼠模型，在总共四个周期(5.7 mg/kg/周期静脉注射)中每三周给药一次，我们的团队能够测试两种运动处方对心肺和身体成分结果的影响。这个新的模型基于临床DOX处方，解决了DOX啮齿动物给药方案的几个局限性，包括给药剂量、给药频率和给药途径[1]。根据已建立的大鼠和人类之间的剂量转换计算[4]对剂量进行定标，相当于每个周期40毫克/平方米，累积剂量为160毫克/平方米。所使用的运动处方是基于目前使用的临床试验
Doxorubicin (DOX) is a highly effective chemotherapeutic agent used in the treatment of many solid tumor, blood and gynecological cancers. However, its use is associated with both acute and chronic adverse cardiovascular events which negatively impact cancer patient quality of life and long-term survivorship [1]. Although there are cardiovascular differences between rodents and humans, primarily related to the large variation in heart rate across species, there are distinct advantages to utilizing small rodents to model human disease [2]. In the case of DOX chemotoxicity, the ability to assess cardiac damage, cardiorespiratory capacity and body composition has allowed for improvements in the translational potential of rodent models of acute and chronic DOX toxicity, while also allowing for investigation at the molecular level [1]. In addition, the smaller amount of drug and shorter time period needed for these studies allows for increased productivity in understanding the mechanisms of DOX cardiotoxicity and in testing potential therapeutic countermeasures [3].Utilizing a rat model where DOX was administered every three weeks for a total of four cycles (5.7 mg/kg/cycle intravenously), our team was able to test the effect of two exercise prescriptions on cardiorespiratory and body composition outcomes. This novel model was adapted based on clinical DOX prescription and addresses several limitations of DOX rodent dosing protocols including dose administered, frequency of administration and route of administration [1]. The dose was scaled based on established dose conversion calculations between rats and humans [4] and equates to 40 mg/m2 each cycle for a cumulative dose of 160 mg/m2. The exercise prescriptions utilized were based on current clinical trials utilizing