# Dysfunction in Cardiovascular Autonomic Modulation Caused by Chronic Use of Ketamine Hydrochloride Can Be Prevented by Aerobic Exercise Training in Wistar Rats

## TL;DR

Aerobic exercise can prevent heart issues caused by long-term ketamine use in rats, suggesting exercise could help people exposed to ketamine.

## Contribution

This study shows aerobic training can counteract ketamine-induced cardiovascular dysfunction in a rat model.

## Key findings

- Chronic ketamine increased blood pressure and reduced baroreflex sensitivity in sedentary rats.
- Aerobic exercise preserved autonomic function and improved baroreflex sensitivity in ketamine-treated rats.
- Trained rats showed similar heart rate variability to controls despite ketamine exposure.

## Abstract

Background/Objectives: Ketamine, widely used for its anesthetic and analgesic properties, has been linked to cardiotoxic effects, particularly with chronic use. Prolonged ketamine exposure may impair cardiovascular function, while aerobic exercise is known to promote protective cardiovascular adaptations. This study aimed to evaluate whether aerobic training can mitigate the deleterious cardiovascular effects of chronic ketamine administration in rats. Methods: Twenty-four Wistar rats were randomly assigned to four groups: sedentary control (S), trained control (T), sedentary with ketamine (S-ket), and trained with ketamine (T-ket). Ketamine was administered intraperitoneally at a dose of 10 mg/kg, three times per week for six weeks. Aerobic training was conducted on a treadmill in the trained groups throughout the protocol. At the end of the experiment, cardiac function was assessed by echocardiography. Additionally, animals were cannulated in the carotid artery and jugular vein to measure blood pressure, baroreflex sensitivity, and heart rate variability using a data acquisition system (2 kHz, Windaq DATAQ). Results: Rats in the S-ket group showed elevated systolic arterial pressure and reduced baroreflex sensitivity compared to controls. Aerobic training attenuated these effects. Baroreflex sensitivity improved (bradycardic reflex—S: −1.7 ± 0.3; S-ket: −0.7 ± 0.1; T: −1.3 ± 0.2; T-ket: −1.3 ± 0.1), and cardiovascular autonomic function was preserved (total power—S: 45.6 ± 6.3; S-ket: 18.3 ± 2.1; T: 44.1 ± 5.7; T-ket: 38.9 ± 8.4) in trained animals. Conclusions: Aerobic exercise mitigates cardiovascular impairments caused by chronic ketamine exposure in rats, suggesting its potential as a non-pharmacological intervention to counteract ketamine-induced cardiotoxicity. These findings support incorporating exercise into treatment strategies for individuals chronically exposed to ketamine.