Efeitos da estimulação elétrica transcutânea do nervo vago sobre marcadores autonômicos, hemodinâmicos, metabólicos e inflamatórios em pacientes com síndrome metabólica

Abstract

INTRODUCTION: Metabolic Syndrome (MetS) is a cluster of conditions: central obesity, augmented glucose levels, dyslipidemia (elevated triglycerides, low HDL-C) and high blood pressure; chronic inflammation is the main physiopathological component. In the last decade, many studies have demonstrated that vagal, cholinergic parasympathetic stimulation reduces the inflammatory response is different scenarios. This knowledge led to the proposition of the concept of the “cholinergic anti-inflammatory reflex” as a mechanism. Activation of this anti-inflammatory reflex can be acquired pharmacologically or by direct vagal stimulation. Although anticholinesterase agents may be effective, less expensive alternatives with fewer side effects are worth investigating, especially transcutaneous electrical stimulation of the vagus nerve (TESVN). OBJECTIVE: to investigate the acute (after 1 single 30-minute session) and chronic (after 8 sessions) effects of TESVN on the components of cardiovascular autonomic modulation and hemodynamic parameters, and in the chronic phase, also on metabolic and inflammatory variables, in patients with MetS. METHODS: This is a prospective, open, randomized 2:1 (treatment group and control group, respectively) interventional clinical study, with both sexes included and aged 18 - 60 years, who present MetS criteria. All patients were formally evaluated to exclude different conditions playing a role in the inflammatory state, pregnancy included. A total of 30 patients were included and randomized; 20 patients (treatment group, TG) received 30-minute TESVN (NEMOS®device) once a week for 8 weeks;10 patients (control group, CG) were evaluated at the beginning of the study and after 2 months. The region stimulated was the cymba conchae of the left ear. The electrical stimulus consisted of a pulse width of 500ms and a stimulation frequency of 25 Hz. The variables analyzed were anthropometric data, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), total peripheral resistance, beat-to-beat evaluated with Finomiter®. Heart Rate Variability (HRV) was analyzed in the time domain (SDRR - Standard deviation of RR intervals and RMSSD- Root mean square of successive RR interval differences) and in the frequency domain spectral analysis ( components LF%, HF%, LF (nu), HF (nu) and LF / HF ratio). Blood samples were collected for biochemical analysis and quantification of endothelial cell markers, monocytes (flow cytometry - FACS) and cytokine quantification (ELISA). STATISTICS: The results were analyzed using the IBM SPSS program (Stastistical Package for the Social Science) 20.0. The normality of the data was tested with the Kolmogorov-Smirnov (KS) test. The Student t test was applied to analyze paired and unpaired samples. For the between groups analysis, the ANOVA test of repeated measures, followed by the Bonferroni post hoc test were used. The differences were considered statistically significant if p ≤ 0.05. Parametric data were presented as mean and standard deviation. RESULTS: after one single session of TESVN the TG showed a decreased HR both in the consultation measurement (72 ± 7 vs 69 ± 8; p=0,022) and in the beat-by-beat measurement (70 ± 8 vs 67 ± 8; p=0,011); a better sympathovagal balance characterized by an augmented HF (nu) (50 ± 13 vs 55 ± 15; p=0,035) and by a reduced LF(nu) (50 ± 13 vs 45 ± 15; p=0,040) along with a reduced LF/HF (1,4 ± 0,9 vs 1,1± 0,7; p=0,010). In the chronic evaluation, comparing the basal versus the after 8 weeks moments, there was a significant difference in the behavior of the following variables between the TG and CG (interaction p <0.05). In the TG, a reduction in consultation and beat-by-beat measurements of, respectively: SBP (137 ± 21 vs 121 ± 11; p=0,001 and 138 ± 20 vs 127 ± 14; p=0,017), DBP(81 ± 10 vs 77 ± 8; p=0,012 and 78 ± 8 vs 74 ± 7; p=0,031) and HR (72 ± 7 vs 68 ± 8; p=0,024 and 70 ± 8 vs 66 ± 8; p=0,009). An augmented HF% (34 ± 14 vs 43 ± 19; p=0,026) and HF(nu) (50 ± 13 vs 60 ± 15; p=0,008), a decreased LF% (32 ± 7 vs 26 ± 8; p=0,025) and LF(nu) (50 ± 13 vs 40 ± 15; p=0,008), and a reduction in the LF/HF ratio (1,4 ± 0,9 vs 0,8 ± 0,6; p=0,026), besides a reduction in the LF (%) [Blood Pressure Variability] (36 ± 13 vs 28 ± 13; p=0,013); there was an increase in the average percentages of CD14% (24 ± 17 vs 52 ± 17; p = 0.049), CD31% (42 ± 19 vs 63 ± 14; p = 0.035) and CD309% (1.2 ± 0.9 vs 2.4 ± 1.0; p = 0.045), and significant reduction of CD16% (27 ± 11 vs 13 ± 5; p = 0.003), indicating a modulation in circulating immune and endothelial cells. No significant variation was observed when comparing the two moments of analysis in the CG (p> 0.05). The mean values of pro-inflammatory cytokines (TNF-α and IL-6) and the lymphocyte / neutrophil ratio did not show significant variations (p <0.05). There was a significant reduction in triglyceride values (141 ± 38 vs 124 ± 32; p = 0.014) in the TG. CONCLUSION: Acute TESVN modulated hemodynamic and autonomic parameters of patients with MS, and a weekly session of TESVN, for a period of 8 weeks, accentuated the changes described, also promoting the recruitment of peripheral circulating immune (classic and non-classic monocytes) and endothelial (circulating and progenitor) cells in these patients.