Feitosa Larissa Andrade de Sá, Carvalho Jéssica Dos Santos, Dantas Cácia Oliveira, de Souza Diego Santos, de Vasconcelos Carla Maria Lins, Miguel-Dos-Santos Rodrigo, Lauton-Santos Sandra, Quíntans-Júnior Lucindo José, Santos Márcio Roberto Viana, de Santana-Filho Valter Joviniano, Barreto André Sales
Department of Physiology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
Department of Health Education, Federal University of Sergipe, Lagarto, Sergipe, Brazil.
Cardiovasc Toxicol. 2021 May;21(5):365-374. doi: 10.1007/s12012-020-09627-w. Epub 2021 Jan 2.
Doxorubicin (DOX) is an anticancer chemotherapy drug that is widely used in clinical practice. It is well documented that DOX impairs baroreflex responsiveness and left ventricular function and enhances sympathetic activity, cardiac sympathetic afferent reflexes and oxidative stress, which contribute to hemodynamic deterioration. Because resistance training (RT)-induced cardioprotection has been observed in other animal models, the objective of this study was to assess the effects of RT during DOX treatment on hemodynamics, arterial baroreflex, cardiac autonomic tone, left ventricular function and oxidative stress in rats with DOX-induced cardiotoxicity. Male Wistar rats were submitted to a RT protocol (3 sets of 10 repetitions, 40% of one-repetition maximum (1RM) of intensity, 3 times per week, for 8 weeks). The rats were separated into 3 groups: sedentary control, DOX sedentary (2.5 mg/kg of DOX intraperitoneal injection, once a week, for 6 weeks) and DOX + RT. After training or time control, the animals were anesthetized and 2 catheters were implanted for hemodynamic, arterial baroreflex and cardiac autonomic tone. Another group of animals was used to evaluate left ventricular function. We found that RT in DOX-treated rats decreased diastolic arterial pressure, heart rate, sympathetic tone and oxidative stress. In addition, RT increased arterial baroreflex sensitivity, vagal tone and left ventricular developed pressure in rats with DOX-induced cardiotoxicity. In summary, RT is a useful non-pharmacological strategy to attenuate DOX-induced cardiotoxicity.
多柔比星（DOX）是一种抗癌化疗药物，在临床实践中广泛应用。有充分的文献记载，DOX会损害压力感受性反射反应和左心室功能，并增强交感神经活动、心脏交感传入反射和氧化应激，这些都会导致血流动力学恶化。由于在其他动物模型中已观察到抗阻训练（RT）诱导的心脏保护作用，本研究的目的是评估在DOX治疗期间进行RT对DOX诱导的心脏毒性大鼠的血流动力学、动脉压力感受性反射、心脏自主神经张力、左心室功能和氧化应激的影响。雄性Wistar大鼠接受RT方案（3组，每组10次重复，强度为一次重复最大值（1RM）的40%，每周3次，共8周）。大鼠被分为3组：久坐对照组、DOX久坐组（腹腔注射2.5mg/kg DOX，每周一次，共6周）和DOX+RT组。在训练或时间控制后，将动物麻醉并植入2根导管，用于测量血流动力学、动脉压力感受性反射和心脏自主神经张力。另一组动物用于评估左心室功能。我们发现，在DOX治疗的大鼠中进行RT可降低舒张压、心率、交感神经张力和氧化应激。此外，RT可提高DOX诱导的心脏毒性大鼠的动脉压力感受性反射敏感性、迷走神经张力和左心室舒张末压。总之，RT是一种减轻DOX诱导的心脏毒性的有用的非药物策略。
