Autonomic tone imbalance plays an important role in the patophysiology of the heart disease (1). A noninvasive tool that allows study of the autonomic cardiovascular modulation is the analysis of heart rate variability (HRV) (2). The alterations in autonomic modulation may be an initiating mechanism underlying the onset of cardiovascular diseases (3). Thus we aimed to test the hypothesis that HRV could be used for early detection of cardiomyopathy. A rodent model of heart failure induced by doxorubicin (DOX), otherwise an effective drug for the cancer treatment, was used in our study. Adult male Wistar rats were treated for 2 weeks with saline (control, n=7) or doxorubicin (1,5mg DOX/kg per week) (DOX group, n=7). In the early period after DOX treatment (7 days after the last application) (4) rats were anesthetized with ketamine (75mg/kg) and xylazine (9mg/kg) and standard 6 channel ECG (Cardiax, IMEDE, Budapest, Hungary) was measured for 3 minutes using subcutaneous needle electrodes. During the autopsy, hearts were gathered for histological examination. The experiment was approved by the National Animal Ethical Committee and conducted in accordance with the European Convention for the protection of vertebrate animals used for experimental purposes. HRV was analyzed in time and frequency domaine (SA aHRV, Nevrokard, Medistar, Slovenia) and One way ANOVA was applied to find significant changes between groups. Power spectrum analysis was evaluated by the total power and by the power of two spectral bands: low frequency component (LF: 0.25-0.75 Hz) and high frequency component (HF: 0.75-3 Hz) according to previous studies (5). The LF/HF ratio was also calculated. Administration of DOX significantly decreased parasympathetically mediated HF component of HRV expressed in normalized units (64.02±2.87 compared to 78.18±5.01 in control rats, P < 0.05) and increased normalized LF component of HRV (31.85±2.24 compared to 20.28±3.44 in control rats, P < 0.05), resulting in an overall increased LF/HF ratio (0.51±0.05 compared to 0.28±0.08 in control rats, P < 0.05). No changes were found in heart rate and time domaine HRV indexes. In all DOX treated animals early myocardial lesions were found, histologically classified as myofibrillar loss, parenchymal degeneration and lymphoid infiltration. Our study confirmed that the modulation of autonomic nervous system activity accompanied the development of heart failure in rodents and could reflect subtle microscopic changes characteristic for the early phase of the disease. Our results recommend HRV as a novel tool for early detection of cardiomyopathy.
Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCA070
Poster Communications: Early heart rate variability alterations in rodent model of cardiomyopathy
N. Potocnik1, M. Perše2, A. Cerar2, R. injac3
1. Institute of physiology, Medical faculty, Ljubljana, Slovenia. 2. Institute of Pathology, Medical faculty, Ljubljana, Slovenia. 3. Institute of Pharmaceutical Biology, Faculty of Pharmacy, Ljubljana, - Please Select -, Slovenia.
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Where applicable, experiments conform with Society ethical requirements.