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Mukvych VV, Severynovska OV. Effect of caffeine on heart rate variability parameters in female rats with doxorubicin-induced cardiomyopathy. Bìol Tvarin. 2025; 27 (1): 27–33. DOI: 10.15407/animbiol27.01.027.
https://doi.org/10.15407/animbiol27.01.027
Received 24.01.2025 ▪ Revision 10.03.2025 ▪ Accepted 20.03.2025 ▪ Published online 11.04.2025

Effect of caffeine on heart rate variability parameters in female rats with doxorubicin-induced cardiomyopathy

V. V. Mukvych, O. V. Severynovska
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Oles Honchar Dnipro National University, 72 Nauky Ave., Dnipro, 49045, Ukraine

Cardiotoxicity remains a significant limitation in the clinical application of chemotherapeutic agents, particularly anthracyclines. Doxorubicin (DOX), a widely used representative of this group, exhibits potent antitumor activity and is commonly administered in the treatment of various malignant tumors. One of the modern, non-invasive, and informative methods for assessing the functional state of the cardiovascular system is heart rate variability (HRV) analysis. In the context of searching for means to correct doxorubicin-induced cardiomyopathy, there is growing interest in studying the effects of natural compounds with potential cardioprotective properties. Caffeine, at low and moderate doses, is capable of exerting antioxidant effects and demonstrating potential cardioprotective activity. The study was conducted on 36 sexually mature female Wistar rats weighing 250±50 g. Healthy animals were randomly divided into three groups (n=12 per group): GROUP I (control) received physiological saline (1 mg/kg) via oral gavage; group II received doxorubicin at a dose of 1 mg/kg body weight intraperitoneally once a week for 4 weeks; group III received caffeine at a dose of 25 mg/kg body weight daily via oral gavage, along with doxorubicin at a dose of 1 mg/kg intraperitoneally once a week for 4 weeks. The electrocardiogram (ECG) was recorded in female rats using a “Cardiolab” electrocardiographic complex for a wide range of cardiological studies (HAI-Medica, Kharkiv, Ukraine). Thus, the administration of doxorubicin to female rats led to statistically significant changes in all HRV parameters, indicating the development of autonomic imbalance. In female rats of the second group, compared to the control, a significant increase was observed in heart rate (HR), mode (Mo), mode amplitude (AMo), vegetative balance index (VBI), and stress index (SI), along with a significant decrease in variation range (VR), root mean square of successive differences (RMSSD), and the percentage of NN intervals differing by more than 50 ms (pNN50). These changes suggest a predominance of sympathetic activity and reduced parasympathetic influence. In female rats that received caffeine in combination with doxorubicin, a partial normalization of HRV parameters was observed, approaching the values recorded in the control group, particularly HR, Mo, and VR. Meanwhile, AMo, VBI, and SI remained significantly elevated compared to the control group, but showed a significant decrease relative to the second group. These findings indicate the potential modulatory effect of caffeine on the autonomic regulation of heart rhythm in female rats with doxorubicin-induced cardiomyopathy. Caffeine, at the given dosage, helps prevent or attenuate autonomic disturbances caused by this chemotherapeutic agent.

Key words: cytotoxicity, doxorubicin-induced cardiomyopathy, caffeine, stimulant effects, heart rate variability, oxidative stress, female rats

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