Breast cancer (BC) is the most common cancer among women. Advances in BC therapy have improved the survival and quality of life of BC patients. However, these improvements are accompanied by cardiac dysfunction that may occur in a subset of patients and compromise chemotherapy continuation. Cardiac dysfunction might be due to an increase in sympathetic (SNS) tone promoted by chemotherapy, contributing to left ventricular ejection fraction decrease. Different preventive strategies, such physical exercise, and β-blockers, have been proposed to maintain the physiological homeostasis. At present, the methods used are insufficient and do not have enough sensitivity so it is not possible to accurately predict which patients will be affected. Thereby it is not clear what is the most effective preventive approach to maintain the physiological homeostasis in these patients. Using animal experiments is possible to develop and functionally characterize a doxorubicin (DOX) treatment model to deeply evaluate it effect in cardiac function and to compare the efficacy of two different approaches to prevent negative outcomes: one pharmacological, using atenolol (ATN), a β1 selective antagonist without antioxidant properties, and other non-pharmacological, using a treadmill training in an animal model of DOX. Healthy female Wistar rats, aged >12 weeks, were divided into 4 groups: Doxorubicin (n=13) (DOX; ip. cumulative dose 8 mg/kg, 1 time/week, for 4 weeks), DOX with physical exercise (n=8) (DOX + EX; treadmill, 22 cm/seg for 30 minutes, 5 times/week), DOX with Atenolol (n=10) (DOX + ATN: DOX, ip. cumulative dose 8 mg/kg, 1 time/week and 4 mg/ml; ATN, oral administration, 5 times/week, for 4 weeks) and controls (n=7) (ip. with saline solution). Echocardiography measurements were recorded at baseline and 1 week after of treatment and blood pressure (BP), cardiac (HR) and respiratory (RF) frequency, baro- and chemoreflexes were evaluated under anaesthesia. Our results reveal that DOX treatment triggered a significant decrease in BP and HR, caused hypopnea, decreased baro- and chemoreflexes, without evidence of sympatho excitation. These changes can be explained by the decline in cardiac function, respiratory muscle weakness, autonomic dysfunction and vascular changes induces by DOX. During treatment with DOX, the physical activity protocol countered some of the adverse effects caused by DOX. It normalized BP, HR and RF to physiological values, and decreases the loss in baroreflex gain. Chemoreflex sensitivity, sympathetic and parasympathetic activities remained similar. Systolic and diastolic pressures and cardiac output increased after exercise. This might be due to an increase in stroke volume due to longer diastoles as showed by echocardiography despite total peripheral resistance was not evaluated. ATN treatment, similar to physical activity effect, also increased baroreflex gain and RF to normal values, causing also a clear tendency to maintain BP values. Although these results are still preliminary and complementary data is still needed, with these results we can conclude that lifestyle changes, such as physical exercise, can improve cardiovascular health and is more effective than atenolol in counteracting the adverse effects of DOX treatment.
Future Physiology 2021 (Virutal) (2021) Proc Physiol Soc 47, PC01
Poster Communications: Preventing cardiotoxicity: Lifestyle changes or pharmacological interventions? Preliminary results in a doxorubicin animal model
Filipa Machado1, Ângela Amaro-Leal1, 2, Ana I. Afonso1, 2, Vera Geraldes1, 2, Isabel Rocha1, 2
1 Centro Cardiovascular da Universidade de Lisboa, Lisboa, Portugal 2 Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal
View other abstracts by:
Where applicable, experiments conform with Society ethical requirements.