Effects of aerobic exercise training on cardiovascular damage induced by ketamine hydrochloride in Wistar rats

Abstract

Ketamine hydrochloride is a drug widely used to treat depression, the most mentally disabling disease in the world. However, there is increasing evidence of cardiovascular damage resulting from the chronic use of ketamine. While regular practice of physical activity has been increasingly recommended as an adjunct in the treatment of depression, physical training promotes beneficial effects on the cardiovascular system. Therefore, the hypothesis of this study is that physical training can mitigate and/or prevent the harmful effects of ketamine on the cardiovascular system. Thus, the aim of this study was to evaluate the effects of aerobic physical training on cardiac morphometry and function, hemodynamic parameters and baroreflex sensitivity in Wistar rats treated with ketamine hydrochloride. For this, 24 Wistar rats were divided into 4 groups (n=6 in each): control (S), trained (T), sedentary treated with ketamine hydrochloride (SK) and trained treated with ketamine hydrochloride (TK). The treatment with ketamine hydrochloride was performed 3 times a week, for 6 weeks (ip, 10mg/kg). The physical training was aerobic on a treadmill (50-70% of the maximum running capacity, 1 hour/day, 5 days/week, 6 weeks). At the end of the protocol, the animals were submitted to echocardiography analysis and cannulation for direct recording of the arterial pressure (AP) and then, baroreflex sensitivity was evaluated. The results demonstrate that chronic treatment with ketamine hydrochloride induces reduction in left ventricular shortening fraction (S: 35.4±1.7; T: 35.7±2.3; SK: 31.5±1.6; TK: 27.9±1.3), increase in systolic (S: 147±2.2; T: 153±2.5; SK: 161±2.8; TK: 155±2.8) and diastolic (S: 97±2.2; T: 103±0.8; SK: 107±3.6; TK: 103±1.5) arterial pressure, increased heart rate (S: 361±2.4; T: 365±8.1; SK: 401±18.1; TK: 354±10.0), and impaired baroreflex tachycardic response (S: 3.0±0.18; T: 3.1±0.18; SK: 2.3±0.06; TK: 3.1±0.10). On the other hand, aerobic physical training seems to be promising to prevent hemodynamic damage, since ketamine-trained animals did not present such damages. In addition, TF promoted resting bradycardia (groups T and TK). These results demonstrate the protective role of physical training, preventing the onset of cardiovascular damage after chronic use of ketamine hydrochloride, suggesting that physical training should be recommended as an adjunct to the treatment of patients using this drug.