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Impact of exercise training and carvedilol on cardiovascular parameters in doxorubicin treated rats
Session:
Posters (Sessão 2 - Écran 3) - Ciência Básica
Speaker:
Ana Isabel Afonso
Congress:
CPC 2022
Topic:
O. Basic Science
Theme:
36. Basic Science
Subtheme:
36.2 Basic Science - Cardiac Biology and Physiology
Session Type:
Pósters Electrónicos
FP Number:
---
Authors:
Ana i. Afonso; â. Amaro-Leal; f. Machado; i. Rocha; v. Geraldes
Abstract
<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">Some conditions like cancer and its treatment, can have a big impact on cardiovascular health. Drugs like doxorubicin (DOX) are highly effective in cancer treatment but accompanied by dose-dependent side effects, including autonomic and cardiovascular toxicity. Some types of adjuvant therapies, particularly non-pharmacological, such as exercise training (ET), and pharmacological, such β-blockers, are usually combined with chemotherapy in order to maintain physiological homeostasis in cancer patients, improving their autonomic and cardiac functions. In our work, we compared the effectiveness of two approaches individually: pharmacological intervention, using carvedilol (CVD), and a non-pharmacological intervention, ET protocol using treadmill training in an animal model of doxorubicin. Female Wistar rats were divided into 4 groups: Doxorubicin (DOX; ip. cumulative dose 16mg/kg, 1time/week, for 4 weeks), DOX with ET (DOX+EX; treadmill, 25cm/seg for 30min, 5 times/week), DOX with CVD (DOX+CVD; 10mg/kg, oral, 5 times/week, for 4 weeks) and controls (CTL; NaCl 0.9%, ip.). At the end of the protocol, animals were anaesthetised and blood pressure (BP), electrocardiogram, heart rate (HR) and respiratory frequency (RF) were recorded. Baroreflex gain, BEI, BRS and chemoreflex sensitivity were calculated and HRV were determined. Our results reveal that DOX treatment triggered hypotension: a significant decrease in systolic BP (CTL: 150±5; DOX: 103±10 mmHg) and mean BP (CTL: 129±3; DOX: 90±10 mmHg) as well as in HR (CTL: 379±54; DOX: 288±53 bpm), compared to the CTL group. During DOX treatment, the ET protocol counteracts some of the adverse effects induced by DOX, normalizing the systolic (122±29 mmHg), mean BP (94±20 mmHg) and HR (350±22 bpm). CVD administration during DOX treatment significantly restored HR close to physiological values (369±16bpm). DOX treatment led to an increase in baroreflex gain compared to the CTL group. CVD treatment, like the ET effect, decreased baroreflex gain compared to the DOX group (DOX: 4,74±2,8; DOX+EX: 0,50±0,07 and DOX+CVD: 0,55±0,06 bpm/mmHg), also restoring BEI, BRS and SDNN to normal values. No significant changes in chemoreflex sensitivity, RF and frequency domain indices were observed. <span style="background-color:white"><span style="color:black">Overall, the present results suggest that, during DOX therapy, ET has an evident beneficial effect on BP values. However, both ET and CVD are good strategies to prevent baroreflex disfunction and maintain normal HR, thus preserving cardiovascular homeostasis.</span></span></span></span></p>
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