Effect of doxycycline in autonomic modulation of the heart, assessed by heart rate variability, in rats with myocardial infarction

Abstract

Treatment with doxycycline (DOXI) reduces ventricular remodeling and decreases the susceptibility of arrhythmias after myocardial infarction (MI), probably due to its inhibitory effect on metalloproteinases, inflammatory mediators, and oxidative stress. We evaluated the effect of DOXI on heart rate variability (HRV) in rats with MI. Infarcted rats (coronary ligation) or control animals (sham-operated), were treated with DOXI (30 mg/kg/day) or vehicle for 4 weeks (N=7-10/group). Rats were implanted with subcutaneous electrodes and, on the following day, had ECG recorded for 30 min. Series of RR intervals were generated to calculate HRV indices. DOXI-treated control rats had lower heart rate (HR) than vehicle-treated counterparts (327±7 vs. 352±7 bpm). Infarcted rats, treated or not, had similar heart rate (344±7 and 350±6 bpm). The standard deviation of RR intervals was similar among groups, but the differences between successive RR (RMSSD) were smaller in DOXI-treated sham-operated rats (4.0±0.5 vs. 6.3±0.9 ms). No differences were observed in RMSSD in rats with MI. Spectral analysis showed that the LF/HF ratio was lower in DOXI-treated control rats (0.32±0.05 vs. 0.62 ± 0.07). There was no difference in the LF/HF ratio in infarcted rats treated with DOXI or vehicle. The symbolic analysis, as described by Porta et al., showed a lower occurrence of 0V patterns (19±4 vs. 33±3%) and a higher 2UV (38±5 vs. 22±2%) in sham-operated rats that received DOXI. In rats with MI, DOXI symbolic indices were found to be similar. Our findings strongly suggest that 4-weeks of treatment with DOXI lead to a change in sympathovagal balance to the parasympathetic side. Curiously this effect was seen only in sham-operated but not in infarcted rats. Funding Sources: Fundação de Amparo à Pesquisa do Estados de São Paulo - FAPESP, 2020/06043-7. Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq, Process 306994/2021-6. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.