This study aimed to evaluate autonomic cardiovascular modulation and baroreflex control of heart rate (HR) in Wistar audiogenic rats (WAR), an epileptic rat strain. We studied spontaneous baroreflex (sequence method) as well as reflex changes in HR evoked by phenylephrine or nitroprusside‐induced changes in arterial pressure (AP). Blockers of autonomic receptors (atropine and propranolol) were used to measure cardiac autonomic tone. Pulse interval (PI) and AP variability analyses were performed by FFT spectral analysis to evaluate cardiovascular sympathovagal modulation. In WAR, AP and HR were higher (109±2 mmHg and 366±9 bpm) as compared with Wistar rats (101±2 mmHg and 326±10 bpm). Power in the low frequency (0.2–0.8 Hz) band, a marker of sympathetic activity, was higher in the AP and PI spectra of WAR than in those of Wistar rats. High frequency (0.8–3 Hz) power of PI spectra, which is linked to cardiac vagal modulation, was lower in WAR. Both strains showed similar vagal tone (91±13 vs. 94±11 bpm) but sympathetic tone was higher in WAR (30±4 vs. 14±4 bpm). No differences were found in the gains of evoked (1.32±0.1 vs. 1.35±0.2 ms/mmHg) or spontaneous (1.34±0.2 vs. 2.04±0.2 ms/mmHg) baroreflex sensitivity. Higher AP and HR are well known to be associated with sympathetic predominance and with threatening cardiovascular events, which are typical causes of sudden unexpected death in epilepsy. Support: FAPESP, CNPq.

Male C57BL mice were submitted to sinoaortic denervation (SAD), or sham surgery, implanted with catheters into femoral artery and jugular vein and let recover for 5 days. After basal recording of arterial pressure (AP) and pulse interval (PI) mice received cardiac autonomic receptor blockers methylatropine or propranolol (n=8–11 in each group). PI changes due to methylatropine or propranolol were measured as cardiac vagal and sympathetic tone, respectively. AP variability was calculated by standard deviation of successive values (SDNN) of systolic AP and PI variability determined by SDNN as well as by the square root of the mean squared differences of successive values of PI (RMSSD). Mean AP and SDNN of SAP was higher in SAD (149±3 and 10.0±0.5 mmHg) as compared to intact mice (136±2 and 6.5±0.4 mmHg). PI was similar between groups (104±3 vs 104±2 ms) while SDNN and RMSSD of PI were lower in SAD (5.4±0.7 and 2.0±0.2 ms) as compared to intact mice (8.2±0.8 and 2.7±0.3 ms). Atropine did not change PI of SAD (100±4 to 98±4 ms), while slightly decreased PI of control mice (103±2 to 96±2 ms, p<0.05). The increase in PI elicited by propranolol was marked higher in SAD (98±6 to 144±9 ms) than in intact mice (98±4 to 124±3 ms). Five days after SAD mice showed mild hypertension with marked increase in AP variability and cardiac sympathetic tone.Support: FAPESP, CNPq and CAPES.

Introduction The pathogenesis of Chronic Chagas Cardiomyopathy (CCC) is not yet fully elucidated. However, dysautonomia is one of the factors involved, in addition to being the essential mechanism in the pathogenesis of the Digestive Form of Chagas Disease (DFCD). The prognostic value of dysautonomia remains speculative, and there are no correlative studies of dysautonomia in CCC and DFCD. Purpose This study has three aims: a) to investigate in patients with CCC the relationship between cardiac dysautonomia, indirectly studied by heart rate variability (HRV), and the prognostic stratification assessed by the Rassi score; b) to compare the HRV in groups with isolated CCC and with the mixed form, i.e. CCC associated with DFCD; c) to evaluate the power of combining HRV indices to predict the risk class of each patient, using machine learning. Methods Thirty-one patients with CCC were classified into three risk groups (low, intermediate and high) according to their Rassi score and had two electrocardiograms (ECG) recorded, i.e. the conventional 12-lead and a single lead, the latter for a period of 10 to 20 minutes. From the single lead ECG, two equally sized RR series were generated and 31 HRV indices were calculated from each. The HRV was then compared between the three risk groups and also regarding the presence or not of concomitant digestive impairment. Taking HRV indices as inputs, four machine learning models were compared in its ability to predict the risk class of each patient. A previous step of attribute selection (sequential feature selection) was applied to identify the most relevant HRV indices for each algorithm. Results Comparing the HRV indices in the three risk groups obtained with the Rassi score, the phase entropy is decreased [0.91 (0.90, 0.91) vs 0.87 (0.86, 0.89); p=0.039] and the percentage of inflection points is increased [66.4 (63.5, 71.2) vs 58.2 (53.4, 63.3); p=0.032] in patients in the high-risk group, compared to the low-risk group. Of the 31 patients with CCC, 14 had the mixed form of the disease, i.e. with associated digestive impairment. In the latter, the triangular interpolation of the RR interval histogram decreased significantly [78.1 (62.5, 101.6) vs 121.1 (80.1, 146.5), p=0.046], while the absolute power in the low-frequency band decreased with strong trend to statistical significance [28.5 (17.1, 97.5) vs 86.9 (44.1, 171.7), p=0.06]. The best predictive model for each risk group was obtained with the Support Vector Machine, reaching an overall F1-score of 0.61. Conclusions The worst prognosis, indicated by the Rassi score, is associated with increased heart rate fragmentation. The combination of HRV indices enhanced the accuracy of the risk stratification. Compared to CCC the mixed form of Chagas' disease displays a decrease in the components of slow heart rate oscillation, suggesting a higher degree of sympathetic autonomic denervation associated with parasympathetic impairment. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): São Paulo Research Foundation (FAPESP)

To detect possible alterations of the baroreflex arch, we assessed the expression of c‐Fos in the NTS and PVN of L‐NAME‐induced hypertensive rats submitted to electrical stimulation of the aortic depressor nerve (ADN) in conscious state. Rats were treated for 14 days with L‐NAME (n=7), D‐NAME (n=5) or tap water (CONTROL; n=6). The animals were equipped with catheters in the femoral artery and vein, and a pair of electrodes for intermittent (5s on/10s off) electrical stimulation (1mA, 2ms and 60Hz) during 20 min. L‐NAME treated rats showed higher arterial pressure and heart rate than D‐NAME and CONTROL rats. The hypotensive response and bradycardia due to electrical stimulation did not differ among groups. The density of c‐Fos in the intermediate and commissural caudal NTS, and magnocelular and parvocelular portions of the PVN was higher in L‐NAME treated rats. In conclusion, electrical stimulation of the ADN activated more effectively neurons in the NTS and PVN of L‐NAME induced hypertensive rats. These findings suggest a greater buffering effect of the NTS upon the PVN in this hypertensive model.Supported by CAPES, CNPq and FAPESP.

It was recently developed a transgenic animal model with overexpression of cholinergic neurotransmission. This mouse, named ChAT-ChR2-EYFP, has several extra copies of the vesicular acetylcholine transporter (VAChT) gene and exhibits three-fold increase in the release of acetylcholine. However, the consequences of overexpression of VAChT protein to the cardiovascular system have not yet been characterized. Therefore, we have investigated the effects of the overexpression of the gene of VAChT on arterial pressure (AP) and heart rate (HR) as well as the autonomic cardiovascular regulation. Mice were assigned into two groups: Wild-type (WT, n=7) and ChAT-ChR2-EYFP (n=7). These animals were anesthetized (isoflurane) and implanted with probes to record AP by telemetry. After 10 days, the mice had basal AP and HR recorded continuously. Assessment of the autonomic function was conducted throughout the following approaches: 1) cardiac sympathovagal balance evaluated by HR responses to methylatropine and propranolol; 2) overall HR variability; 3) spontaneous baroreflex sensitivity by the sequence analysis. ChAT-ChR2-EYFP mice showed lower basal HR (461±8 vs. 502±14 bpm, p<0.01) but similar AP as compared to WT mice. ChAT-ChR2-EYFP mice exhibited higher vagal tone (Δbpm, 169±14 vs. 117±6, p=0.03) and lower HR after double autonomic blockade (IHR, 456±8 vs. 509±11 bpm, p<0.001). HR variability was similar between groups (SDNN: 88±16 vs. 65±7 ms; RMSSD: 11.4±1 vs. 9.7±0.5 ms). However, the baroreflex sensitivity (7.5±1.5 vs. 4.1±0.5 ms/mmHg, p=0.05) was higher in ChAT-ChR2-EYFP mice. Altogether, the results show that the cardiovascular autonomic regulation of ChAT-ChR2-EYFP mice is characterized by higher parasympathetic tone, combined with a lower basal HR and IHR. Moreover, these mice present greater baroreflex sensitivity.