P106Chronic hyperpolarization-activated inward current blockade increases both sympathetic and parasympathetic activation

Funding Acknowledgements: This work was supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNCS – UEFISCDI, project number PN-II-RU Introduction: The effects of the hyperpolarization-activated inward current blocker ivabradine on sympatho-vagal balance remain controversial. Previous studies have suggested either sympathetic or parasympathetic dominance in ivabradine-treated individuals, or even no change. Purpose: We aimed to assess the effects of chronic ivabradine treatment on heart rate variability indexes. Methods: Twenty-eight healthy male Wistar rats were divided into two groups, receiving vehicle (Control; n=13) or ivabradine (IVA; 10 mg/kg/day; n=15) in the drinking water for three consecutive weeks. All rats were implanted with radiotelemetry ECG devices and 72-h continuous ECG monitoring was performed in freely moving rats. Heart rate variability indexes in the time and frequency domains were evaluated. Results: As expected, ivabradine significantly decreased resting heart rate (351±29 bpm in Control vs. 294±31 bpm in IVA; p<0.0001). Chronic ivabradine treatment was associated with increased standard deviation of normal-to-normal intervals (SDNN; 27.3±6.4 ms vs. 17.9±3.8 ms; p<0.0001), root mean square differences of successive R-R intervals (RMSSD; 5.7±1.4 ms vs. 2.7±0.6 ms; p<0.0001), proportion of successive R-R intervals difference >50 ms (pNN50; 0.29±0.09% vs. 0.07±0.04%; p<0.0001), as well as with increased total power (44.2±17.3 ms2 vs. 16.9±7.1 ms2; p<0.0001), normalized high (HF)- (28.6±12.5% vs. 16.3±5.3%; p<0.01) and low (LF)-frequency (6.1±1.5% vs. 4.3±1.9%; p=0.01) power. LF/HF ratios were not affected by ivabradine (0.2±0.1 vs. 0.3±0.1; p=0.43).