Genetic markers of cardiac autonomic neuropathy in the Kazakh population.

BACKGROUND: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation. Recent evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome potentially serving as precursors. This study aims to identify genetic markers associated with CAN development in the Kazakh population by investigating the SNPs of specific genes. MATERIALS AND METHODS: A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE "Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan". 7 SNPs of genes FTO, PPARG, SNCA, XRCC1, FLACC1/CASP8 were studied. Statistical analysis was performed using Chi-square methods, calculation of odds ratios (OR) with 95% confidence intervals (CI), and logistic regression in SPSS 26.0. RESULTS: Among the SNCA gene polymorphisms, rs2737029 was significantly associated with CAN, almost doubling the risk of CAN (OR 2.03(1.09-3.77), p = 0.03). However, no statistically significant association with CAN was detected with the rs2736990 of the SNCA gene (OR 1.00 CI (0.63-1.59), p = 0.99). rs12149832 of the FTO gene increased the risk of CAN threefold (OR 3.22(1.04-9.95), p = 0.04), while rs1801282 of the PPARG gene and rs13016963 of the FLACC1 gene increased the risk twofold (OR 2.56(1.19-5.49), p = 0.02) and (OR 2.34(1.00-5.46), p = 0.05) respectively. rs1108775 and rs1799782 of the XRCC1 gene were associated with reduced chances of developing CAN both before and after adjustment (OR 0.24, CI (0.09-0.68), p = 0.007, and OR 0.43, CI (0.22-0.84), p = 0.02, respectively). CONCLUSION: The study suggests that rs2737029 (SNCA gene), rs12149832 (FTO gene), rs1801282 (PPARG gene), and rs13016963 (FLACC1 gene) may be predisposing factors for CAN development. Additionally, SNPs rs1108775 and rs1799782 (XRCC1 gene) may confer resistance to CAN. Only one polymorphism rs2736990 of the SNCA gene was not associated with CAN.

Novel predictive approaches for drug-induced convulsions in non-human primates using machine learning and heart rate variability analysis.

Drug-induced convulsions are a major challenge to drug development because of the lack of reliable biomarkers. Using machine learning, our previous research indicated the potential use of an index derived from heart rate variability (HRV) analysis in non-human primates as a biomarker for convulsions induced by GABAA receptor antagonists. The present study aimed to explore the application of this methodology to other convulsants and evaluate its specificity by testing non-convulsants that affect the autonomic nervous system. Telemetry-implanted males were administered various convulsants (4-aminopyridine, bupropion, kainic acid, and ranolazine) at different doses. Electrocardiogram data gathered during the pre-dose period were employed as training data, and the convulsive potential was evaluated using HRV and multivariate statistical process control. Our findings show that the Q-statistic-derived convulsive index for 4-aminopyridine increased at doses lower than that of the convulsive dose. Increases were also observed for kainic acid and ranolazine at convulsive doses, whereas bupropion did not change the index up to the highest dose (1/3 of the convulsive dose). When the same analysis was applied to non-convulsants (atropine, atenolol, and clonidine), an increase in the index was noted. Thus, the index elevation appeared to correlate with or even predict alterations in autonomic nerve activity indices, implying that this method might be regarded as a sensitive index to fluctuations within the autonomic nervous system. Despite potential false positives, this methodology offers valuable insights into predicting drug-induced convulsions when the pharmacological profile is used to carefully choose a compound.

Effect of the early diastolic blood pressure response to the head-up tilt test on the recurrence of benign paroxysmal positional vertigo.

BACKGROUND: Otolith organ acts complementarily with the autonomic nervous system to maintain blood pressure. However, the effect of blood pressure variability in the autonomic nervous system on otolith organ has not yet been determined. This study aimed to verify the hypothesis that blood pressure variability in the autonomic nervous system affects the recurrence of benign paroxysmal positional vertigo (BPPV), which is the most common disease of the vestibular organs, by using the head-up tilt test (HUTT). METHODS: This study included 432 patients diagnosed with idiopathic BPPV. The follow-up period for all patients was 12 months. Age, sex, hypertension, diabetes and recurrence were analyzed. The HUTT parameters were divided into a group of patients whose average diastolic blood pressure increased in the upright position compared to supine position during the HUTT (DBP1) and a group of patients whose average diastolic blood pressure decreased in the upright position compared to supine position during the HUTT (DBP2). Model selection, general loglinear analysis, and logit loglinear analysis were performed using a hierarchically progressing loglinear analysis. RESULTS: In summary, the group with increased average diastolic blood pressure (DBP1) showed a higher tendency for BPPV recurrence compared to the group with decreased diastolic blood pressure (DBP2) in the upright position during the HUTT, although the difference was not statistically significant (p = 0.080). However, in males, the DBP1 group demonstrated a significantly higher recurrence rate of BPPV than the DBP2 group during the HUTT (95% CI, -20.021 to -16.200; p < 0.001). CONCLUSIONS: It is presumed that poor autonomic nervous system response through vestibulosympathetic reflex maintains elevated diastolic blood pressure in the upright position during the HUTT. This variability is assumed to affect the recurrence of BPPV.

Association between COVID-19 exposure and autonomic nervous system dysfunction in apparently healthy adults: an observational study.

OBJECTIVE: Coronavirus disease (COVID-19) is a respiratory disease caused by SARS-CoV-2, which complicates the functioning of multiple systems, including the autonomic nervous system (ANS), causing dysautonomia. Investigation of dysautonomia and its association with exposure to COVID-19 is limited in healthy people. Therefore, the study aimed to investigate the relationship between ANS dysautonomia and coronavirus exposure and compare the ANS function between exposed and non-exposed to COVID-19. SUBJECTS AND METHODS: The study involved 141 participants, with a mean age of 18-24.5 years, 83% male (49.6% exposed to COVID-19). The ANS was measured using a composite autonomic symptom scale (COMPASS-31) questionnaire and heart rate variability (HRV) using photoplethysmography. Exposure to COVID-19 was investigated using two national health-status tracking and COVID-19 exposure applications, "Sehhaty" and "Twakkalna". RESULTS: A significantly inverse weak correlation between COMPASS-31 scores and COVID-19 exposure (r=-0.2, p=0.04). No significant association was found between HRV and COVID-19 exposure. COMPASS-31 scores for the exposed group (median=15, n=70) were significantly higher than those for the non-exposed group (median=12, n=71), U=1,913.5, p=0.03. Height (r=-0.4, p=0.002) and gender (r=0.3, p=0.001) were moderately correlated with COMPASS-31 among the exposed group. CONCLUSIONS: These findings indicated that exposure to COVID-19 was associated with poorer ANS scores measured via COMPASS-31. Additionally, exposure to COVID-19 resulted in higher dysautonomia symptoms than non-exposed. Height and gender differences contribute to the severity of dysautonomia among exposed people.

Effects of Vitamin D Supplementation on Central Hemodynamic Parameters and Autonomic Nervous System in Obese or Overweight Individuals. / Efeitos da Suplementação de Vitamina D sobre Parâmetros Hemodinâmicos Centrais e Sistema Nervoso Autônomo em Indivíduos com Obesidade ou Sobrepeso.

BACKGROUND: Previous studies have been inconsistent in demonstrating beneficial cardiovascular effects of vitamin D supplementation. OBJECTIVE: To evaluate the effects of vitamin D3 supplementation on central hemodynamic parameters and autonomic activity in obese/overweight individuals with low vitamin D levels (<30ng/dl). METHODS: Adults 40-65 years old with body mass index ≥25<40 kg/m2 were enrolled in this prospective, randomized, double-blind clinical trial (NCT05689632). Central hemodynamics was assessed using the oscillometric method (Mobil-O-Graph®), and heart rate variability using a Polar heart rate monitor (Kubios® software). Patients (n=53) received a placebo in the control group (CO, n=25) or vitamin D3 (VD, n=28) 7000 IU/day, and were evaluated before (W0) and after 8 weeks (W8) with a significance level of 0.05. RESULTS: The groups were homogeneous regarding age (51±6 vs 52±6 years, p=0.509) and vitamin D levels (22.8±4.9 vs 21.7±4.5ng/ml, p=0.590). At W8, the VD group had significantly higher levels of vitamin D (22.5 vs 35.6ng/ml, p<0.001). Only the VD group showed a significant reduction in systolic blood pressure (SBP; 123±15 vs 119±14mmHg, p=0.019) and alkaline phosphatase (213±55 vs 202±55mg/dl, p=0.012). The CO group showed an increase in augmentation pressure (AP: 9 vs 12 mmHg, p=0.028) and augmentation index (AIx: 26 vs 35%, p=0.020), which was not observed in the VD group (AP: 8 vs 8 mmHg, AIx: 26 vs 25%, p>0.05). VD group showed an increase in the parasympathetic nervous system index (PNSi) (-0.64±0.94 vs -0.16±1.10, p=0.028) and the R-R interval (866±138 vs 924±161 ms, p= 0.026). CONCLUSION: In this sample, eight weeks of daily vitamin D supplementation resulted in an improvement in blood pressure levels and autonomic balance.

FUNDAMENTO: Estudos prévios têm sido inconsistentes em demonstrar efeitos cardiovasculares benéficos da suplementação de vitamina D. OBJETIVO: Avaliar efeitos da suplementação de vitamina D3 sobre parâmetros hemodinâmicos centrais e atividade autonômica em indivíduos obesos/sobrepeso e baixos níveis de vitamina D (<30ng/dl). MÉTODOS: Ensaio clínico prospectivo, randomizado, duplo-cego (NCT05689632), adultos 40-65 anos com índice de massa corporal ≥25<40 kg/m2. Hemodinâmica central avaliada por método oscilométrico (Mobil-O-Graph®), variabilidade da frequência cardíaca utilizando frequencímetro Polar (software Kubios®). Os pacientes (n=53) receberam placebo no grupo controle (CO, n=25) ou vitamina D3 (VD, n=28) 7000 UI/dia, avaliados antes (S0) e após 8 semanas (S8) com nível de significância de 0,05. RESULTADOS: Os grupos foram homogêneos na idade (51±6 vs. 52±6 anos, p=0,509) e níveis de vitamina D (22,8±4,9 vs. 21,7±4,5ng/ml, p=0,590). Na S8, o grupo VD apresentou níveis significativamente maiores de vitamina D (22,5 vs. 35,6ng/ml, p<0,001). Apenas o grupo VD mostrou redução significativa da pressão arterial sistólica (PAS; 123±15 vs. 119±14mmHg, p=0,019) e fosfatase alcalina (213±55 vs. 202±55mg/dl, p=0,012). O grupo CO mostrou elevação da pressão de aumento (AP: 9 vs. 12mmHg, p=0,028) e do índice de incremento (Aix: 26 vs. 35%, p=0,020), o que não foi observado no grupo VD (AP: 8 vs. 8mmHg, Aix: 26 vs. 25%, p>0,05). Grupo VD apresentou aumento no índice do sistema nervoso (iSN) parassimpático (-0,64±0,94 vs. -0,16±1,10, p=0,028) e no intervalo R-R (866±138 vs. 924±161ms, p=0,026). CONCLUSÃO: Nesta amostra, a suplementação diária de vitamina D durante oito semanas resultou em melhora dos níveis pressóricos, parâmetros hemodinâmicos centrais e do equilíbrio autonômico.

Direct and indirect effects of adiposity on markers of autonomic nervous system activity in older adults.

Several cardiovascular disease (CVD) risk factors (e.g., hypertension, poor glycemic control) can affect and be affected by autonomic nervous system (ANS) activity. Since excess adiposity can influence CVD development through its effect on hypertension and diabetes mellitus, it is important to determine how adiposity and altered ANS activity are related. The present study employed structural equation modeling to investigate the relation between adiposity and ANS activity both directly and indirectly through biological variables typically associated with glycemic impairment and cardiac stress in older adults. Utilizing the Atherosclerosis Risk in Communities (ARIC) dataset, 1,145 non-smoking adults (74±4.8 yrs, 62.8% female) free from known CVD, hypertension, and diabetes and not currently taking beta-blockers were evaluated for fasting blood glucose (FBG), insulin, and HbA1c concentrations, waist circumference (WC), blood pressure (BP), and markers of ANS activity. WC was recorded just above the iliac crest and was used to reflect central adiposity. Resting 2-minute electrocardiograph recordings, pulse wave velocity, and ankle-brachial index data were used to assess the root mean square of successive differences in RR intervals (RMSSD) and the pre-ejection period (PEP), markers of parasympathetic and sympathetic activity, respectively. FBG, insulin, and HbA1c inferred a latent variable termed glycemic impairment (GI), whereas heart rate and diastolic BP inferred a latent variable termed cardiac stress (CS). The structural equation model fit was acceptable [root mean square error of approximation = 0.050 (90% CI = .036, .066), comparative fit index = .970, Tucker Lewis Index = 0.929], with adiposity having both significant direct (ß = 0.208, p = 0.018) and indirect (ß = -.217, p = .041) effects on PEP through GI. Adiposity displayed no significant direct effect on RMSSD. CS displayed a significant pathway (ß = -0.524, p = 0.035) on RMSSD, but the indirect effect of WC on RMSSD through CS did not reach statistical significance (ß = -0.094, p = 0.137). These results suggest that adiposity's relation to ANS activity is multifaceted, as increased central adiposity had opposing direct and indirect effects on markers of sympathetic activity in this population of older adults.

Long-COVID autonomic syndrome in working age and work ability impairment.

Long-COVID19 has been recently associated with long-sick leave and unemployment. The autonomic nervous system functioning may be also affected by SARS-CoV-2, leading to a chronic autonomic syndrome. This latter remains widely unrecognized in clinical practice. In the present study, we assessed the occurrence of Long-COVID19 Autonomic Syndrome in a group of active workers as well as the relationships between their autonomic dysfunction and work ability. This prospective observational study was conducted during the 2nd wave of the pandemic in Italy. Forty-five patients (53.6 ± 8.4 years; 32 M) hospitalized for COVID19, were consecutively enrolled at the time of their hospital discharge (T0) and followed-up for 6 months. Autonomic symptoms and work ability were assessed by COMPASS31 and Work Ability Index questionnaires at T0, one (T1), three and six (T6) months after hospital discharge and compared to those retrospectively collected for a period preceding SARS-CoV-2 infection. Clinical examination and standing test were also performed at T1 and T6. One in three working-age people developed a new autonomic syndrome that was still evident 6 months after the acute infection resolution. This was associated with a significant reduction in the work ability. Recognition of Long-COVID19 Autonomic Syndrome may promote early intervention to facilitate return to work and prevent unemployment.

Effects of acute hyperoxia on autonomic function and coronary tone in patients with peripheral artery disease.

Numerous studies have shown that oxidative stress plays an important role in peripheral artery disease (PAD). Prior reports suggested autonomic dysfunction in PAD. We hypothesized that responses of the autonomic nervous system and coronary tone would be impaired in patients with PAD during exposure to acute hyperoxia, an oxidative stressor. In 20 patients with PAD and 16 healthy, sex- and age-matched controls, beat-by-beat heart rate (HR, from ECG) and blood pressure (BP, with Finometer) were recorded for 10 min during room air breathing and 5 min of hyperoxia. Cardiovagal baroreflex sensitivity and HR variability (HRV) were evaluated as measures of autonomic function. Transthoracic coronary echocardiography was used to assess peak coronary blood flow velocity (CBV) in the left anterior descending coronary artery. Cardiovagal baroreflex sensitivity at rest was lower in PAD than in healthy controls. Hyperoxia raised BP solely in the patients with PAD, with no change observed in healthy controls. Hyperoxia induced an increase in cardiac parasympathetic activity assessed by the high-frequency component of HRV in healthy controls but not in PAD. Indices of parasympathetic activity were lower in PAD than in healthy controls throughout the trial as well as during hyperoxia. Hyperoxia induced coronary vasoconstriction in both groups, while the coronary perfusion time fraction was lower in PAD than in healthy controls. These results suggest that the response in parasympathetic activity to hyperoxia (i.e., oxidative stress) is blunted and the coronary perfusion time is shorter in patients with PAD.NEW & NOTEWORTHY Patients with peripheral artery disease (PAD) showed consistently lower parasympathetic activity and blunted cardiovagal baroreflex sensitivity compared with healthy individuals. Notably, hyperoxia, which normally boosts parasympathetic activity in healthy individuals, failed to induce this response in patients with PAD. These data suggest altered autonomic responses during hyperoxia in PAD.

Impaired autonomic function and somatosensory disturbance in patients with treated autoimmune thyroiditis.

Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition referred to as "syndrome T". Peripheral neuropathy, described in untreated thyroid disease, could be a contributing mechanism. We analysed autonomic and somatosensory function in 29 patients with AIT and treated hypothyroidism and 27 healthy volunteers. They underwent heart rate variability (HRV) analysis and quantitative sensory testing (n = 28), comprising 13 parameters of small and large nerve fibre function and pain thresholds. Autonomic cardiovascular function was assessed in rest, deep respiration and orthostasis. Additionally, biomarkers for autoimmunity and thyroid function were measured. Anxiety, depression and QoL were assessed using validated questionnaires. 36% of the patients showed at least one sign of somatosensory small or large fibre dysfunction. 57% presented with mild hyperalgesia to at least one stimulus. Several markers of autonomic function and some detection thresholds were related to the antibody titres. Anxiety, depression scores and QoL correlated to antibody titres and HRV measures. Autonomic and somatosensory dysfunction indicate that in treated hypothyroidism and AIT a subgroup of patients suffers from neuropathic symptoms leading to impaired QoL. Additionally, mild hyperalgesia as a possible sensitisation phenomenon should be considered a target for symptomatic treatment.

Hypoxic and Autonomic Mechanisms from Sleep-Disordered Breathing Leading to Cardiopulmonary Dysfunction.

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder. Its prevalence has increased due to increasing obesity and improved screening and diagnostic strategies. OSA overlaps with cardiopulmonary diseases to promote intermittent hypoxia and autonomic dysfunction. Intermittent hypoxia increases the risk for oxidative stress and inflammation, which promotes endothelial dysfunction and predisposes to atherosclerosis and other cardiovascular complications. OSA is associated with an increased sympathetic nervous system drive resulting in autonomic dysfunction leading to worsening of cardiopulmonary diseases. Cardiovascular diseases are observed in 40% to 80% of OSA patients. Therefore, it is essential to screen and treat cardiovascular diseases.

Heart rate variability to track autonomic nervous system health in young children: Effects of physical activity and cardiometabolic risk factors.

Evidence for a key role of dysregulated autonomic nervous system (ANS) activity in maladaptive stress response/recovery and non-communicable disease development is extensive. Monitoring ANS activity via regular heart rate variability (HRV) measurement is growing in popularity in adult populations given that low HRV has been associated with ANS dysregulation, poor stress response/reactivity, increased cardiometabolic disease risk and early mortality. Although cardiometabolic disease may originate in early life, regular HRV measurement for assessing ANS activity in childhood populations, especially those consisting of children < 6 years of age, remains largely unpractised. A greater understanding of ANS activity modifiers in early life may improve analysis and interpretation of HRV measurements, thereby optimising its usefulness. Taking into consideration that HRV and ANS activity can be improved via daily engagement in physical activity (PA), this review will discuss the ANS and HRV, ANS activity modifiers, cardiometabolic disease risk factors and PA as they relate to childhood/adolescent populations (≤ 18 years old).

Different heart rate variability profile during sleep in mid-later life adults with remitted early-onset versus late-onset depression.

BACKGROUND: In mid-later life adults, early-onset and late-onset (i.e., onset ≥50 years) depression appear to be underpinned by different pathophysiology yet have not been examined in relation to autonomic function. Sleep provides an opportunity to examine the autonomic nervous system as the physiology changes across the night. Hence, we aimed to explore if autonomic profile is altered in mid-later life adults with remitted early-onset, late-onset and no history of lifetime depression. METHODS: Participants aged 50-90 years (n = 188) from a specialised clinic underwent a comprehensive clinical assessment and completed an overnight polysomnography study. General Linear Models were used to examine the heart rate variability differences among the three groups for four distinct sleep stages and the wake after sleep onset. All analyses controlled for potential confounders - age, sex, current depressive symptoms and antidepressant usage. RESULTS: For the wake after sleep onset, mid-later life adults with remitted early-onset depression had reduced standard deviation of Normal to Normal intervals (SDNN; p = .014, d = -0.64) and Shannon Entropy (p = .004, d = -0.46,) than those with no history of lifetime depression. Further, the late-onset group showed a reduction in high-frequency heart rate variability (HFn.u.) during non-rapid eye movement sleep stage 2 (N2; p = .005, d = -0.53) and non-rapid eye movement sleep stage 3 (N3; p = .009, d = -0.55) when compared to those with no lifetime history. LIMITATIONS: Causality between heart rate variability and depression cannot be derived in this cross-sectional study. Longitudinal studies are needed to examine the effects remitted depressive episodes on autonomic function. CONCLUSION: The findings suggest differential autonomic profile for remitted early-onset and late-onset mid-later life adults during sleep stages and wake periods. The differences could potentially serve as peripheral biomarkers in conjunction with more disease-specific markers of depression to improve diagnosis and prognosis.

Effects of Blood Flow Restriction Resistance Training on Autonomic and Endothelial Function in Persons with Parkinson's Disease.

Background: Autonomic dysfunction precedes endothelial dysfunction in Parkinson's disease (PD) and causes blood pressure and circulation abnormalities that are highly disruptive to one's quality of life. While exercise interventions have proven helpful for motor symptoms of PD, improving associated non-motor symptoms is limited. Low-intensity resistance training with blood flow restriction (LIRT-BFR) improves autonomic dysfunction in non-PD patients and high-intensity resistance training (HIRT) is recommended for motor symptom improvements for people with PD (PwPD). Objective: To determine the effects of LIRT-BFR and HIRT on homocysteine and autonomic and endothelial function in PwPD and to determine the hemodynamic loads during LIRT-BFR and HIRT in PwPD using a novel exercise protocol. Methods: Thirty-eight PwPD were assigned LIRT-BFR, HIRT or to a control (CNTRL) group. The LIRT-BFR and HIRT groups exercised three days per week for four weeks. The LIRT-BFR protocol used 60% limb occlusion pressure (LOP) and performed three sets of 20 repetitions at 20% of the one-repetition maximum (1RM). The HIRT group performed three sets of eight repetitions at 80% 1RM. The CNTRL group was asked to continue their normal daily routines. Results: LIRT-BFR significantly improved orthostatic hypotension (p = 0.026), homocysteine levels (p < 0.001), peripheral circulation (p = 0.003), supine blood pressure (p = 0.028) and heart rate variability (p = 0.041); LIRT-BFR improved homocysteine levels (p < 0.018), peripheral circulation (p = 0.005), supine blood pressure (p = 0.007) and heart rate variability (p = 0.047) more than HIRT; and hemodynamic loads for LIRT-BFR and HIRT were similar. Conclusions: LIRT-BFR may be more effective than HIRT for autonomic and endothelial function improvements in PwPD and hemodynamic loads may be lessened in LIRT-BFR protocols using single-joint exercises with intermittent blood flow restriction. Further research is needed to determine if non-motor symptoms improve over time and if results are sustainable.

From Social Stress and Isolation to Autonomic Nervous System Dysregulation in Suicidal Behavior.

PURPOSE OF REVIEW: In this narrative review we wanted to describe the relationship of autonomic nervous system activity with social environment and suicidal spectrum behaviors. RECENT FINDINGS: Patients with suicidal ideation/suicide attempt have higher sympathetic nervous system (SNS) and lower parasympathetic nervous system (PNS) activity in resting conditions and during acute stress tasks compared with patients without suicidal ideation/suicide attempt. Death by suicide and violent suicide attempt also are related to SNS hyperactivation. Similarly, a SNS/PNS imbalance has been observed in people with childhood trauma, stressful life events or feelings of loneliness and isolation. Social support seems to increase PNS control and resilience. Due to the importance of the social context and stressful life events in suicidal behavior, SNS/PNS imbalance could act as a mediator in this relationship and be a source of relevant biomarkers. Childhood trauma and stressful life events may impair the autonomic nervous system response in suicidal patients. Loneliness, isolation and social support may act as moderators in acute stress situations.

Exploring Cardiovascular Autonomic Function before and after Chronic Deep Brain Stimulation in Parkinson's Disease.

BACKGROUND: Blood pressure control in Parkinson's disease (PD) under subthalamic deep brain stimulation (STN-DBS) is influenced by several intertwined aspects, including autonomic failure and levodopa treatment. OBJECTIVE: To evaluate the effect of chronic STN-DBS, levodopa, and their combination on cardiovascular autonomic functions in PD. METHODS: We performed cardiovascular reflex tests (CRTs) before and 6-months after STN-DBS surgery in 20 PD patients (pre-DBS vs. post-DBS). CRTs were executed without and with medication (med-OFF vs. med-ON). RESULTS: CRT results and occurrence of neurogenic orthostatic hypotension (OH) did not differ between pre- and post-DBS studies in med-OFF condition. After levodopa intake, the BP decrease during HUTT was significantly greater compared to med-OFF, both at pre-DBS and post-DBS evaluation. Levodopa-induced OH was documented in 25% and 5% of patients in pre-DBS/med-ON and post-DBS/med-ON study. CONCLUSION: Chronic stimulation did not influence cardiovascular responses, while levodopa exerts a relevant hypotensive effect. The proportion of patients presenting levodopa-induced OH decreases after STN-DBS surgery.

Ivabradine restores tonic cardiovascular autonomic control and reduces tachycardia, hypertension and left ventricular inflammation in post-weaning protein malnourished rats.

Malnutrition results in autonomic imbalance and heart hypertrophy. Overexpression of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in the left ventricles (LV) is linked to hypertrophied hearts and abnormal myocardium automaticity. Given that ivabradine (IVA) has emerging pleiotropic effects, in addition to the widely known bradycardic response, this study evaluated if IVA treatment could repair the autonomic control and cardiac damages in malnourished rats. AIM: Assess the impact of IVA on tonic cardiovascular autonomic control and its relationship with hemodynamics regulation, LV inflammation, and HCN gene expression in post-weaning protein malnutrition condition. MAIN METHODS: After weaning, male rats were divided into control (CG; 22 % protein) and malnourished (MG; 6 % protein) groups. At 35 days, groups were subdivided into CG-PBS, CG-IVA, MG-PBS and MG-IVA (PBS 1 ml/kg or IVA 1 mg/kg) received during 8 days. We performed jugular vein cannulation and electrode implant for drug delivery and ECG registration to assess tonic cardiovascular autonomic control; femoral cannulation for blood pressure (BP) and heart rate (HR) assessment; and LV collection to evaluate ventricular remodeling and HCN gene expression investigation. KEY FINDINGS: Malnutrition induced BP and HR increases, sympathetic system dominance, and LV remodeling without affecting HCN gene expression. IVA reversed the cardiovascular autonomic imbalance; prevented hypertension and tachycardia; and inhibited the LV inflammatory process and fiber thickening caused by malnutrition. SIGNIFICANCE: Our findings suggest that ivabradine protects against malnutrition-mediated cardiovascular damage. Moreover, our results propose these effects were not attributed to HCN expression changes, but rather to IVA pleiotropic effects on autonomic control and inflammation.

What do we know about the role of menopause in cardiovascular autonomic regulation in hypertensive women?

OBJECTIVE: We investigated the systemic arterial hypertension effects on cardiovascular autonomic modulation and baroreflex sensitivity (BRS) in women with or without preserved ovarian function. METHODS: A total of 120 women were allocated into two groups: middle-aged premenopausal women (42 ± 3 y old; n = 60) and postmenopausal women (57 ± 4 y old; n = 60). Each group was also divided into two smaller groups (n = 30): normotensive and hypertensive. We evaluated hemodynamic and anthropometric parameters, cardiorespiratory fitness, BRS, heart rate variability (HRV), and blood pressure variability. The effects of hypertension and menopause were assessed using a two-way analysis of variance. Post hoc comparisons were performed using the Student-Newman-Keuls test. RESULTS: Comparing premenopausal groups, women with systemic arterial hypertension showed lower BRS (9.1 ± 4.4 vs 13.4 ± 4.2 ms/mm Hg, P < 0.001 ) and HRV total variance (1,451 ± 955 vs 2,483 ± 1,959 ms 2 , P = 0.005) values than normotensive; however, the vagal predominance still remained. On the other hand, both postmenopausal groups showed an expressive reduction in BRS (8.3 ± 4.2 vs 11.3 ± 4.8 ms/mm Hg, P < 0.001) and HRV characterized by sympathetic modulation predominance (low-frequency oscillations; 56% ± 17 vs 44% ± 17, P < 0.001), in addition to a significant increase in blood pressure variability variance (28.4 ± 14.9 vs 22.4 ± 12.5 mm Hg 2 , P = 0.015) compared with premenopausal groups. Comparing both postmenopausal groups, the hypertensive group had significantly lower values ​​of HRV total variance (635 ± 449 vs 2,053 ± 1,720 ms 2 , P < 0.001) and BRS (5.3 ± 2.8 vs 11.3 ± 3.2 ms/mm Hg) than the normotensive. CONCLUSIONS: Hypertensive middle-aged premenopausal women present HRV autonomic modulation impairment, but they still maintain a vagal predominance. After menopause, even normotensive women show sympathetic autonomic predominance, which may also be associated with aging. Furthermore, postmenopausal women with hypertension present even worse cardiac autonomic modulation.

Circadian changes of autonomic function in patients with zoster-associated pain: A heart rate variability analysis.

OBJECTIVE: To investigate the circadian changes of the autonomic function in patients with zoster-associated pain (ZAP). METHODS: A total of 37 patients with ZAP from April 2022 to October 2022 were enrolled as the observation group, and 37 normal volunteers at the same time were selected as the control group. All participants were required to wear a 24-h Holter, which was used to compare the heart rate variability (HRV) between the two groups. HRV analysis involved time- and frequency-domain parameters. RESULTS: There was no statistically significant difference in general information between two groups. Patients with ZAP had an increased mean heart rate and decreased the standard deviation of normal-to-normal (SDNN) R-R interval, the root mean square of the differences (RMSSD) in successive RR interval, low frequency (LF), and high frequency (HF) compared with control groups in all periods (p < .05). The ratio of LF/HF between two groups had no significant difference (p = .245). SDNN had no significant difference between day and night in the control group (p > .05), whereas SDNN of ZAP patients in night period was reduced than that in day period (p < .001). The level of RMSSD during the day was lower than those at night in the control group (p < .05), whereas no significant difference of RMSSD between two periods was observed in patients with ZAP (p > .05). CONCLUSION: The results of this study indicated that ZAP contributes to the decline of autonomic nervous system (ANS) function, especially parasympathetic components. The patients with ZAP lost parasympathetic advantage and had a worse ANS during the night.

Biomarker Periodic Repolarization Dynamics Indicates Enhanced Risk for Arrhythmias and Sudden Cardiac Death in Myocardial Infarction in Pigs.

BACKGROUND: Periodic repolarization dynamics (PRD) is an electrocardiographic biomarker that captures repolarization instability in the low frequency spectrum and is believed to estimate the sympathetic effect on the ventricular myocardium. High PRD indicates an increased risk for postischemic sudden cardiac death (SCD). However, a direct link between PRD and proarrhythmogenic autonomic remodeling has not yet been shown. METHODS AND RESULTS: We investigated autonomic remodeling in pigs with myocardial infarction (MI)-related ischemic heart failure induced by balloon occlusion of the left anterior descending artery (n=17) compared with pigs without MI (n=11). Thirty days after MI, pigs demonstrated enhanced sympathetic innervation in the infarct area, border zone, and remote left ventricle paralleled by altered expression of autonomic marker genes/proteins. PRD was enhanced 30 days after MI compared with baseline (pre-MI versus post-MI: 1.75±0.30 deg2 versus 3.29±0.79 deg2, P<0.05) reflecting pronounced autonomic alterations on the level of the ventricular myocardium. Pigs with MI-related ventricular fibrillation and SCD had significantly higher pre-MI PRD than pigs without tachyarrhythmias, suggesting a potential role for PRD as a predictive biomarker for ischemia-related arrhythmias (no ventricular fibrillation versus ventricular fibrillation: 1.50±0.39 deg2 versus 3.18±0.53 deg2 [P<0.05]; no SCD versus SCD: 1.67±0.32 deg2 versus 3.91±0.63 deg2 [P<0.01]). CONCLUSIONS: We demonstrate that ischemic heart failure leads to significant proarrhythmogenic autonomic remodeling. The concomitant elevation of PRD levels in pigs with ischemic heart failure and pigs with MI-related ventricular fibrillation/SCD suggests PRD as a biomarker for autonomic remodeling and as a potential predictive biomarker for ventricular arrhythmias/survival in the context of MI.