Spontaneous Heart Rate Variability Research Articles

Nicotine Formulation Influences the Autonomic and Arrhythmogenic Effects of Electronic Cigarettes.

Evidence is mounting that electronic cigarette (e-cig) use induces cardiac sympathetic dominance and electrical dysfunction conducive to arrhythmias and dependent upon nicotine. A variety of nicotine types and concentrations are available in e-cigs, but their relative cardiovascular effects remain unclear. Here we examine how different nicotine forms (racemic, free base, and salt) and concentrations influence e-cig-evoked cardiac dysfunction and arrhythmogenesis and provide a mechanism for nicotine-salt-induced autonomic imbalance. ECG-telemetered C57BL/6J mice were exposed to filtered air (FA) or e-cig aerosols from propylene glycol and vegetable glycerin solvents either without nicotine (vehicle) or with increasing nicotine concentrations (1%, 2.5%, and 5%) for three 9-minute puff sessions per concentration. Spontaneous ventricular premature beat (VPB) incidence rates, heart rate, and heart rate variability (HRV) were compared between treatments. Subsequently, to test the role of β1-adrenergic activation in e-cig-induced cardiac effects, mice were pretreated with atenolol and exposed to either FA or 2.5% nicotine salt. During puffing and washout phases, ≥2.5% racemic nicotine reduced heart rate and increased HRV relative to FA and vehicle controls, indicating parasympathetic dominance. Relative to both controls, 5% nicotine salt elevated heart rate and decreased HRV during washout, suggesting sympathetic dominance, and also increased VPB frequency. Atenolol abolished e-cig-induced elevations in heart rate and declines in HRV during washout, indicating e-cig-evoked sympathetic dominance is mediated by β1-adrenergic stimulation. Our findings suggest that inhalation of e-cig aerosols from nicotine-salt-containing e-liquids could increase the cardiovascular risks of vaping by inducing sympathetic dominance and cardiac arrhythmias. Exposure to e-cig aerosols containing commercially relevant concentrations of nicotine salts may increase nicotine delivery and impair cardiac function by eliciting β1-adrenoceptor-mediated sympathoexcitation and provoking ventricular arrhythmias. If confirmed in humans, our work suggests that regulatory targeting of nicotine salts through minimum pH standards or limits on acid additives in e-liquids may mitigate the public health risks of vaping.

Liposome-Encapsulated Hemoglobin Vesicle Improves Persistent Anti-arrhythmogenesis through Improving Myocardial Electrical Remodeling and Modulating Cardiac Autonomic Activity in a Hemorrhagic Shock-Induced Rat Heart Model

Shock heart syndrome (SHS) is associated with lethal arrhythmias (ventricular tachycardia/ventricular fibrillation, VT/VF). We investigated whether liposome-encapsulated human hemoglobin vesicles (HbVs) has comparable persistent efficacy to washed red blood cells (wRBCs) for improving arrhythmogenesis in the subacute to chronic phase of SHS. Optical mapping analysis (OMP), electrophysiological study (EPS), and pathological examinations were performed on blood samples from Sprague-Dawley rats following induction of hemorrhagic shock. After hemorrhagic shock, the rats were immediately resuscitated by transfusing 5% albumin (ALB), HbV, or wRBCs. All rats survived for 1 week. OMP and EPS were performed on Langendorff-perfused hearts. Spontaneous arrhythmias and heart rate variability (HRV) were evaluated using awake 24-h telemetry, cardiac function by echocardiography, and pathological examination of Connexin43. OMP showed significantly impaired action potential duration dispersion (APDd) in the left ventricle (LV) in the ALB group whereas APDd was substantially preserved in the HbV and wRBCs groups. Sustained VT/VF was easily provoked by EPS in the ALB group. No VT/VF was induced in the HbV and wRBCs groups. HRV, spontaneous arrhythmias, and cardiac function were preserved in the HbV and wRBCs groups. Pathology showed myocardial cell damage and Connexin43 degradation in the ALB group, all of which were attenuated in the HbV and wRBCs groups. LV remodeling after hemorrhagic shock caused VT/VF in the presence of impaired APDd. Similar to wRBCs, HbV persistently prevented VT/VF by inhibiting persistent electrical remodeling, preserving myocardial structures, and ameliorating arrhythmogenic modifying factors in the subacute to chronic phase of hemorrhagic shock-induced SHS.

Attenuated cardiac autonomic function in humans with high-affinity hemoglobin and compensatory polycythemia.

During hypoxic exposure, humans with high-affinity hemoglobin (and compensatory polycythemia) have blunted increases in heart rate compared with healthy humans with typical oxyhemoglobin dissociation curves. This response may be associated with altered autonomic control of heart rate. Our hypothesis-generating study aimed to investigate cardiac baroreflex sensitivity and heart rate variability among nine humans with high-affinity hemoglobin [6 females, O2 partial pressure at 50% [Formula: see text] (P50) = 16 ± 1 mmHg] compared with 12 humans with typical affinity hemoglobin (6 F, P50 = 26 ± 1 mmHg). Participants breathed normal room air for a 10-min baseline, followed by 20 min of isocapnic hypoxic exposure, designed to lower the arterial partial pressure O2 ([Formula: see text]) to ∼50 mmHg. Beat-by-beat heart rate and arterial blood pressure were recorded. Data were averaged in 5-min periods throughout the hypoxia exposure, beginning with the last 5 min of baseline in normoxia. Spontaneous cardiac baroreflex sensitivity and heart rate variability were determined using the sequence method and the time and frequency domain analyses, respectively. Cardiac baroreflex sensitivity was lower in humans with high-affinity hemoglobin than controls at baseline and during isocapnic hypoxic exposure (normoxia: 7 ± 4 vs. 16 ± 10 ms/mmHg, hypoxia minutes 15-20: 4 ± 3 vs. 14 ± 11 ms/mmHg; group effect: P = 0.02, high-affinity hemoglobin vs. control, respectively). Heart rate variability calculated in both the time (standard deviation of the N-N interval) and frequency (low frequency) domains was lower in humans with high-affinity hemoglobin than in controls (all P < 0.05). Our data suggest that humans with high-affinity hemoglobin may have attenuated cardiac autonomic function.

Association between preoperative autonomic nervous system function and post-induction hypotension in elderly patients: a protocol for a cohort study

IntroductionPost-induction hypotension (PIH), which is prevalent among elderly patients, is associated with adverse perioperative outcomes. As a critical part of blood pressure regulation, baroreflex control is believed to be closely...

Abstract 022: Impaired Parasympathetic Cardiac Modulation In Long-COVID Postural Tachycardia Syndrome

About 1 out of 10 patients infected with Sars-CoV2 have persistent symptoms beyond 4 weeks and some of them meet diagnostic criteria for postural tachycardia syndrome (Long-COVID POTS). The pathophysiology of Long-COVID POTS is unknown, but autonomic dysfunction may play a role. We hypothesize Long-COVID POTS patients have impaired cardiovascular autonomic reflexes and cardiac sympathovagal balance. We conducted a case-control study with patients recruited from the Vanderbilt Autonomic Dysfunction Center and an historical population of healthy controls. Hemodynamic parameters were measured before and during 75° head up tilt. Supine ECG and finger blood pressure were continuously measured for spontaneous heart rate variability analysis. The Low Frequency (0.04-0.15Hz, LF RR ) and High Frequency (0.15-0.4 Hz, HF RR ) oscillatory modulations of sino-atrial node discharge were computed. We included 14 Long-COVID POTS patients and 15 controls matched by age (34 ± 11 vs 28 ± 7; p=0.09) and BMI (26.1 ± 5.3 vs 23.0 ± 2.6; p=0.06). As expected, the orthostatic HR increase was higher in Long-COVID POTS compared to controls (40 ± 18 vs 21 ± 1, p&lt;0.05). Spectral analysis of heart rate variability in 9 patients and 15 controls (Figure) showed that Long-COVID POTS had reduced HF RR (363 ± 420 vs 933 ± 1000 ms 2 ; p&lt;0.05) and similar LF RR (798 ± 596 vs 962 ± 1075 ms 2 ; p=0.68), resulting in a greater LF/HF ratio (3.7 ± 2.9 vs 1.4 ± 1.3; p&lt;0.05). Patients with Long-COVID POTS have reduced markers of cardiovagal modulation, but normal cardiac sympathetic activation. Our results suggest that parasympathetic dysfunction contributes to the pathophysiology of Long-COVID POTS.

Sugar‐Sweetened Soft Drink Consumption Acutely Modifies Cardiovascular Control in Healthy Adults

Long-term consumption of sugar-sweetened soft drinks is associated with an increased prevalence of cardiometabolic diseases. Previous reports demonstrate that consuming a bolus of fructose-sweetened water acutely increases blood pressure variability (BPV) and decreases spontaneous cardiovagal baroreflex sensitivity (cBRS) and heart rate variability (HRV). If caffeinated soft drinks containing high levels of fructose elicit similar responses is unknown. Objective Test the hypothesis that high-fructose corn syrup (HFCS) sweetened soft drink consumption increases BPV and decreases cBRS and HRV compared to water and artificially-sweetened (Diet) and sucrose-sweetened (Sucrose) soft drinks. Methods Twelve subjects (2 females; age 24 ± 4 y; body mass index: 24.1 ± 3.1 kg/m2) completed four randomized, double-blinded trials in which they drank 500 mL of water or commercially available soft drinks matched for taste and caffeine content (~77 mg). Subjects were not naïve to caffeine and consumed 346 ± 481 mL of soft drinks per week. We continuously measured beat-to-beat blood pressure (finger photoplethysmography) and R-R interval (ECG) before and 30 minutes after drink consumption during supine rest for 5 minutes during spontaneous and paced breathing (frequency of 15 breathes/minute). BPV was evaluated using standard deviation, average real variability, and successive variation methods for systolic and diastolic blood pressure. cBRS was assessed using the sequence method for up and down sequences. Overall cBRS was calculated as the average of up and down sequences. HRV was evaluated using the root mean square of successive differences in R-R interval (RMSSD) and the high frequency power component following power spectral density analysis (HF). Due to variation at baseline, data were analyzed as the magnitude of change (∆) from pre-drink consumption using a mixed-effects model with post hoc Sidak's test comparisons. Data are reported as mean ± SD. Results There were no differences between conditions for indices of BPV in standard deviation, average real variability, and successive variation during spontaneous and paced breathing (P≥0.07). Overall cBRS during spontaneous breathing was reduced in the HFCS (-3 ± 5 ms/mmHg) and Sucrose (-3 ± 5 ms/mmHg) trials compared to Water (+1 ± 5 ms/mmHg, P<0.03). Sucrose also elicited greater reductions in overall cBRS during spontaneous breathing compared to Diet (+1 ± 4 ms/mmHg, P=0.01) and HFCS was reduced during down sequences compared to Diet (-3 ± 5 vs. +2 ± 3 ms/mmHg, P=0.057). HFCS evoked greater reductions in RMSSD during paced breathing compared to Water (-26 ± 34 vs. +2 ± 26 ms, P<0.01), but not Diet (-11 ± 26 ms, P=0.43) nor Sucrose (-12 ± 11 ms, P=0.51). There were no differences in HF during paced breathing between HFCS and the other trials (Water: -408 ± 1178; Diet: -62 ± 1270; Sucrose: -871 ± 1549; HFCS: -155 ± 1505 ms2, P≥0.13). Conclusion These findings suggest that in healthy young adults, sugar-sweetened soft drink consumption acutely reduces cBRS and HRV but does not alter BPV.

Effects of high-intensity intervals and moderate-intensity exercise on baroreceptor sensitivity and heart rate variability during recovery.

Numerous studies have examined heart rate variability (HRV) and cardiac baroreceptor sensitivity (BRS) variables during recovery both acutely (under 3 h) and long-term (24, 48, and 72 h) postexercise. However, there is little literature examining HRV and BRS measures between these timepoints. Spontaneous short-term HRV and cardiac BRS measures were collected in 9 participants before and at zero, 1, 2, 4, 6, and 8 h after 3 separate conditions: moderate-intensity continuous exercise (MICE; 45 min at 50% heart rate reserve), high-intensity interval exercise (HIIE; 25 min including ten 1-min intervals at 85% heart rate reserve), and control (30 min quiet rest). HRV measures in the time domain were only affected immediately following HIIE and MICE at hour zero (all p < 0.043), whereas frequency-domain metrics were unaltered (all p > 0.102). These measures were highly consistent across the control day (all p > 0.420). Cardiac BRS was assessed via low-frequency (LF) gain, and revealed reductions following HIIE at hour zero (p < 0.012). Cardiac BRS LF gain remained consistent following MICE and control interventions (all p > 0.280). The common practice of waiting 12 to 24 h is overly conservative as the current findings demonstrate measures return to baseline at ∼60 min after exercise. Moreover, these metrics demonstrated high levels of within- and between-day reliability. Novelty Previously a 12-h minimum restriction from exercise was required before participation in HRV/BRS studies. Recovery from moderate-intensity exercise for HRV and BRS metrics was <60 min; whereas, high-intensity intervals led to alterations for approximately 60 min. Spontaneous HRV and cardiac BRS demonstrated high levels of within-day reproducibility.

Dynamical interaction between heart rate and blood pressure of end-stage renal disease patients evaluated by cross recurrence plot diagonal analysis.

The assessment of spontaneous variability of blood pressure and heart rate is based on specific physiological hypotheses about dynamic features, for example, the baroreflex modulation of heart rate over time in daily life. Usually, arterial baroreflex control of heart rate is explored without delays between blood pressure and heart rate data points, within a narrow range of values, excluding the analysis of saturation regions or low-threshold changes. In this work, we examine the dynamic interactions between systolic blood pressure (SBP) and interbeat interval (IBI), in 15-min length time series and for the first time using the analysis of diagonals derived from a cross-recurrence plots in healthy persons and end-stage renal disease (ESRD) patients. We found that ESRD patients have stronger intermittent dynamical interactions between IBI and SBP, but they lose most of the dynamical interactions. Although healthy subjects exhibit a continuously changing order of precedence between IBI and SBP at different lags, ESRD patients preserve this changing order of precedence only for lags >0 beats.NEW & NOTEWORTHY This study is the first to compare the time-variant pattern of systolic blood pressure (SBP) and interbeat interval (IBI) coupling between ESRD patients and healthy volunteers through the analysis of diagonal in cross-recurrence plots, and in the face of an orthostatic challenge. Our results demonstrated alternant interactions on the order of precedence (IBI → SBP or SBP→ IBI) at different time delays. This pattern is different in resting position and during active standing for the two groups studied, and interestingly, some association patterns are lost in ESRD patients. These patterns of alternant interactions on the order of precedence could be related to autonomic neural activities and cardiovascular synchronization at different scales both in time and space. This could reflect physiological adaptive flexibility of cardiovascular regulation. Losing some association patterns in ESRD may be the result of chronic adjustments of many physiological mechanisms (including chronic sympathetic hyperactivity), which could increase cardiovascular vulnerability to hemodynamic challenges.

Testing the vagal withdrawal hypothesis during light exercise under autonomic blockade: a heart rate variability study.

We performed the first analysis of heart rate variability (HRV) at rest and during exercise under full autonomic blockade on the same subjects, to test the conjecture that vagal tone withdrawal occurs at exercise onset. We hypothesized that between rest and exercise there would be 1) no differences in total power (PTOT) under parasympathetic blockade, 2) a PTOT fall under β1-sympathetic blockade, and 3) no differences in PTOT under blockade of both autonomic nervous system branches. Seven men [24 (3) yr, mean (SD)] performed 5-min cycling (80 W) supine, preceded by 5-min rest during control and with administration of atropine, metoprolol, and atropine + metoprolol (double blockade). Heart rate and arterial blood pressure were continuously recorded. HRV and blood pressure variability were determined by power spectral analysis, and baroreflex sensitivity was determined by the sequence method. At rest, PTOT and the powers of low- and high-frequency components of HRV (LF and HF, respectively) were dramatically decreased with atropine and double blockade compared with control and metoprolol, with no effects on LF-to-HF ratio and on the normalized LF (LFnu) and HF (HFnu). During exercise, patterns were the same as at rest. Comparing exercise with rest, PTOT varied as hypothesized. For systolic and diastolic blood pressure, resting PTOT was the same in all conditions. During exercise, in all conditions, PTOT was lower than in control. Baroreflex sensitivity decreased under atropine and double blockade at rest and under control and metoprolol during exercise. The results support the hypothesis that vagal suppression determined disappearance of HRV during exercise.NEW & NOTEWORTHY This study provides the first demonstration, by systematic analysis of heart rate variability at rest and during exercise under full autonomic blockade on the same subjects, that suppression of vagal activity is responsible for the disappearance of spontaneous heart rate variability during exercise. This finding supports previous hypotheses on the role of vagal withdrawal in the control of the rapid cardiovascular response at exercise onset.

Towards understanding the complexity of cardiovascular oscillations: Insights from information theory

Cardiovascular complexity is a feature of healthy physiological regulation, which stems from the simultaneous activity of several cardiovascular reflexes and other non-reflex physiological mechanisms. It is manifested in the rich dynamics characterizing the spontaneous heart rate and blood pressure variability (HRV and BPV).The present study faces the challenge of disclosing the origin of short-term HRV and BPV from the statistical perspective offered by information theory. To dissect the physiological mechanisms giving rise to cardiovascular complexity in different conditions, measures of predictive information, information storage, information transfer and information modification were applied to the beat-to-beat variability of heart period (HP), systolic arterial pressure (SAP) and respiratory volume signal recorded non-invasively in 61 healthy young subjects at supine rest and during head-up tilt (HUT) and mental arithmetics (MA). Information decomposition enabled to assess simultaneously several expected and newly inferred physiological phenomena, including: (i) the decreased complexity of HP during HUT and the increased complexity of SAP during MA; (ii) the suppressed cardiorespiratory information transfer, related to weakened respiratory sinus arrhythmia, under both challenges; (iii) the altered balance of the information transferred along the two arms of the cardiovascular loop during HUT, with larger baroreflex involvement and smaller feedforward mechanical effects; and (iv) an increased importance of direct respiratory effects on SAP during HUT, and on both HP and SAP during MA. We demonstrate that a decomposition of the information contained in cardiovascular oscillations can reveal subtle changes in system dynamics and improve our understanding of the complexity changes during physiological challenges.

Cooling-evoked hemodynamic perturbations facilitate sympathetic activity with subsequent myogenic vascular oscillations via alpha2-adrenergic receptors.

This study extends our previous work by examining the effects of alpha2-adrenoceptors under cold stimulation involving the increase of myogenic vascular oscillations as increases of very-low-frequency and low-frequency of the blood pressure variability. Forty-eight adult male Sprague-Dawley rats were randomly divided into four groups: vehicle; yohimbine; hexamethonium+yohimbine; guanethidine+yohimbine. Systolic blood pressure, heart rate, power spectral analysis of spontaneous blood pressure and heart rate variability and spectral coherence at very-low-frequency (0.02 to 0.2 Hz), low-frequency (0.2 to 0.6 Hz), and high-frequency (0.6 to 3.0 Hz) regions were monitored using telemetry. Key findings are as follows: 1) Cooling-induced pressor response was attenuated by yohimbine and further attenuated by hexamethonium+yohimbine and guanethidine+yohimbine, 2) Cooling-induced tachycardia response of yohimbine was attenuated by hexamethonium+yohimbine and guanethidine+yohimbine, 3) Different patterns of power spectrum reaction and coherence value compared hexamethonium+yohimbine and guanethidine+yohimbine to yohimbine alone under cold stimulation. The results suggest that sympathetic activation of the postsynaptic alpha2-adrenoceptors causes vasoconstriction and heightening myogenic vascular oscillations, in turn, may increase blood flow to prevent tissue damage under stressful cooling challenge.

Correlation between RR, inter-systolic and inter-diastolic intervals and their differences for the analysis of spontaneous heart rate variability

Analysis of heart rate variability (HRV) is performed through interbeat interval time series derived from either electrocardiographic or arterial pressure (AP) recordings. However, little attention has been given to the reliability of calculating the time series from different sources, i.e. electrocardiogram (ECG) or pulse intervals (PI). Therefore, the present study aimed to evaluate the correlation between interbeat interval time series obtained from RR, inter-systolic (SS) and inter-diastolic (DD) intervals, as well as their impact on indices of HRV calculated from series of RR or PI. Conscious rats previously instrumented with subcutaneous electrodes and a catheter into the femoral artery were subjected to simultaneous ECG and AP recording for 5 min. Correlation and Bland–Altman plots between RR and PI were evaluated. Moreover, HRV was analyzed in time (mean cardiac interval, SDNN and RMSSD) and frequency domain (power in LF and HF spectral bands) as well as by nonlinear approaches (symbolic dynamics and sample entropy). First, RR showed a stronger correlation with PI calculated by DD than SS. Second, most HRV indices showed similar results when calculated with RR or DD series, but not with SS series. Considering RR interval as the gold standard for the calculation of cardiac cycle, when using PI inter diastolic intervals are the better choice to study HRV. These findings are quite relevant, especially when AP recording is used for HRV analysis.

Autonomic dysfunction in multiple sclerosis is better detected by heart rate variability and is not correlated with central autonomic network damage

BackgroundMS-associated autonomic dysfunction (AD) in multiple sclerosis (MS) is poorly understood and the best method for its detection unestablished. We compared classical Ewing battery and newer methods as heart rate variability (HRV) and spontaneous baroreflex sensibility (BRS) to detect AD in MS and related them to central autonomic network (CAN) lesions. MethodsWe enrolled 20 relapsing-remitting MS patients, median age of 36 (interquartile range 32–46) years, disease duration of 5.5 (2.2–6.8) years, Expanded Disability Status Scale (EDSS) score of 1.0 (1.0–1.5) and 20 age- and gender-matched healthy controls. We assessed Ewing battery and spontaneous HRV and BRS. CAN involvement was evaluated by magnetic resonance imaging. ResultsHRV showed both parasympathetic and sympathetic significant impairment in MS (p<0.05). From Ewing battery only isometric test was significantly decreased in MS (p=0.006). Disease duration and severity, lesion burden and CAN involvement were not correlated with laboratorial parameters. ConclusionsOur MS cohort had both sympathetic and parasympathetic dysfunction independently from disease duration, neurological deficits and lesion burden or CAN involvement. HRV analysis maybe more useful than classical Ewing battery to screen AD.

Effects of gravitational acceleration on cardiovascular autonomic control in resting humans.

Previous studies of cardiovascular responses in hypergravity suggest increased sympathetic regulation. The analysis of spontaneous heart rate variability (HRV) parameters and spontaneous baroreflex sensitivity (BRS) informs on the reciprocal balance of parasympathetic and sympathetic regulations at rest. This paper was aimed at determining the effects of gravitational acceleration (a g) on HRV and BRS. Eleven healthy subjects (age 26.6 ± 6.1) were studied in a human centrifuge at four a g levels (1, 1.5, 2 and 2.5 g) during 5-min sessions at rest. We evaluated spontaneous variability of R-R interval (RR), and of systolic and diastolic blood pressure (SAP and DAP, respectively), by power spectral analysis, and BRS by the sequence method, using the BRSanalysis(®) software. At 2.5 g, compared to 1 g, (1) the total power (P TOT) and the powers of LF and HF components of HRV were lower, while the LF/HF ratio was higher; (2) normalized units for LF and HF did not changed significantly; (3) the P TOT, LF and HF powers of SAP were higher; (4) the P TOT and LF power of DAP were higher; and (5) BRS was decreased. These results do not agree with the notion of sympathetic up-regulation supported by the increase in HR and DAP (tonic indices), and of SAP and DAP LF powers (oscillatory indices). The P TOT reduction leads to speculate that only the sympathetic branch of the ANS might have been active during elevated a g exposure. The vascular response occurred in a condition of massive baroreceptive unloading.

Autonomic regulation of cardiovascular system in patients with type 1 diabetes mellitus with arterial hypertension and normal blood pressure

Objective. To determine whether cardiac autonomic neuropathy (CAN) influences the development of arterial hypertension (HTN) in patients with type 1 diabetes mellitus (T1DM). Design and methods. We examined 60 patients with T1DM (37 women and 23 men, mean age 40,3 ± 1,3 years) and 40 healthy controls (21 women and 19 men, mean age 30,0 ± 0,6 years). Clinical symptoms of CAN as well as instrumental parameters were assessed. The following methods were used: spectral analysis of heart rate variability, blood pressure changes during tilt-test, the Valsalva maneuver, test with deep respiration, hand-grip and cold-pressor test, an index 30/15, arterial and cardiopulmonary baroreflexes. Blood pressure monitor (Finometer) and occlusion plethysmograph (Dohn) with parallel registration of electrocardiogram were used for data assessment. Results. Clinical symptoms of CAN had 39 patients with T1DM (65%), in 30 of them CAN was confirmed by instrumental methods. In 9 patients without clinical manifestations CAN was diagnosed instrumentally. The most frequent disorders in T1DM patients were the reduction of spontaneous arterial baroreflex (69%), cardiopulmonary baroreflex (64%), and heart rate variability (49%). HTN was diagnosed in 37 T1DM patients (62%) and was more frequent in patients with autonomic dysfunction (р &lt; 0,05).The patients with CAN had longer duration of HTN (5,7 ± 2,80 vs 2,3 ± 2,80 years, р &lt; 0,05) and higher HTN degree (χ2 = 8,06, р &lt; 0,01) than patients without CAN. Conclusions. Cardiac autonomic neuropathy contributes to the development of HTN in T1DM patients. Implementation of instrumental methods for timely diagnosis of CAN is reasonable in T1DM patients.

Acute and chronic systemic CB1 cannabinoid receptor blockade improves blood pressure regulation and metabolic profile in hypertensive (mRen2)27 rats.

We investigated acute and chronic effects of CB1 cannabinoid receptor blockade in renin‐angiotensin system‐dependent hypertension using rimonabant (SR141716A), an orally active antagonist with central and peripheral actions. In transgenic (mRen2)27 rats, a model of angiotensin II‐dependent hypertension with increased body mass and insulin resistance, acute systemic blockade of CB1 receptors significantly reduced blood pressure within 90 min but had no effect in Sprague‐Dawley rats. No changes in metabolic hormones occurred with the acute treatment. During chronic CB1 receptor blockade, (mRen2)27 rats received daily oral administration of SR141716A (10 mg/kg/day) for 28 days. Systolic blood pressure was significantly reduced within 24 h, and at Day 21 of treatment values were 173 mmHg in vehicle versus 149 mmHg in drug‐treated rats (P < 0.01). This accompanied lower cumulative weight gain (22 vs. 42 g vehicle; P < 0.001), fat mass (2.0 vs. 2.9% of body weight; P < 0.05), and serum leptin (2.8 vs. 6.0 ng/mL; P < 0.05) and insulin (1.0 vs. 1.9 ng/mL; P < 0.01), following an initial transient decrease in food consumption. Conscious hemodynamic recordings indicate twofold increases occurred in spontaneous baroreflex sensitivity (P < 0.05) and heart rate variability (P < 0.01), measures of cardiac vagal tone. The beneficial actions of CB1 receptor blockade in (mRen2)27 rats support the interpretation that an upregulated endocannabinoid system contributes to hypertension and impaired autonomic function in this angiotensin II‐dependent model. We conclude that systemic CB1 receptor blockade may be an effective therapy for angiotensin II‐dependent hypertension and associated metabolic syndrome.

Assessing Methods of Heart Rate Variability

Heart rate variability is significantly associated with cardiovascular complications in various neurological disorders with cardiac impairment. Measures of spontaneous heart rate variability might be different from provocating tests of heart rate variability such as deep breathing and Valsava maneuver. Methods for analysis are divided into time domain methods and frequency domain methods. There are standard deviation of NN interval, standard deviation of average NN interval, root mean square of the successive differences, NN50, and pNN50 in time domain methods. Frequency domain bands can be divided into very low, low, and high frequency. Each variables are influenced by sympathetic and/or parasympathetic activity. (Korean J Clin Neurophysiol 2014;16:49-54)

Chronic baroreflex activation restores spontaneous baroreflex control and variability of heart rate in obesity-induced hypertension.

The sensitivity of baroreflex control of heart rate is depressed in subjects with obesity hypertension, which increases the risk for cardiac arrhythmias. The mechanisms are not fully known, and there are no therapies to improve this dysfunction. To determine the cardiovascular dynamic effects of progressive increases in body weight leading to obesity and hypertension in dogs fed a high-fat diet, 24-h continuous recordings of spontaneous fluctuations in blood pressure and heart rate were analyzed in the time and frequency domains. Furthermore, we investigated whether autonomic mechanisms stimulated by chronic baroreflex activation and renal denervation-current therapies in patients with resistant hypertension, who are commonly obese-restore cardiovascular dynamic control. Increases in body weight to ∼150% of control led to a gradual increase in mean arterial pressure to 17 ± 3 mmHg above control (100 ± 2 mmHg) after 4 wk on the high-fat diet. In contrast to the gradual increase in arterial pressure, tachycardia, attenuated chronotropic baroreflex responses, and reduced heart rate variability were manifest within 1-4 days on high-fat intake, reaching 130 ± 4 beats per minute (bpm) (control = 86 ± 3 bpm) and ∼45% and <20%, respectively, of control levels. Subsequently, both baroreflex activation and renal denervation abolished the hypertension. However, only baroreflex activation effectively attenuated the tachycardia and restored cardiac baroreflex sensitivity and heart rate variability. These findings suggest that baroreflex activation therapy may reduce the risk factors for cardiac arrhythmias as well as lower arterial pressure.

Central sleep apnea indicates autonomic dysfunction in asymptomatic carotid stenosis: a potential marker of cerebrovascular and cardiovascular risk.

Arteriosclerosis related stenosis in the carotid bulb causes autonomic imbalance, likely due to carotid chemoreceptor and baroreceptor dysfunction. The latter are associated with increased cerebrovascular and cardiovascular mortality. Chemoreceptor and baroreceptor dysfunction is also involved in the origin of central sleep apnea syndrome (CSA) in different clinical entities. We hypothesized that CSA is associated with stenosis of the internal carotid artery (ICA). The mechanism of this association is an autonomic imbalance induced by stenosis-mediated chemoreceptor and baroreceptor dysfunction. Cross-sectional prospective study. University-based tertiary referral sleep clinic and research center. Fifty-nine patients with various degrees of asymptomatic extracranial ICA (elCA) (n = 49) and intracranial ICA (ilCA) stenosis (n = 10) were investigated. Polysomnography to detect CSA and analysis of spontaneous heart rate variability (HRV) to detect autonomic imbalance. CSA occurred in 39% of the patients with elCA stenosis but was absent in patients with ilCA stenosis. CSA was present in patients with severe elCA stenosis of > or = 70% on one side. Independent predictors for CSA were severity of stenosis, asymmetric distribution of stenosis between both elCA and autonomic imbalance, namely a decrease of parasympathetic tone. The specific constellation of HRV-parameters indicated increased chemoreceptor sensitivity and impaired baroreflex sensitivity. CSA indicates autonomic dysfunction in patients with asymptomatic elCA stenosis. Detection of CSA may help to identify asymptomatic patients with an increased risk of cerebrovascular or cardiovascular events who particularly benefit from carotid revascularization.

Chronic hepatitis C virus infection associated with autonomic dysfunction

Impaired autonomic function has been described in patients with chronic liver diseases from different aetiologies, and has proven to be a poor prognostic indicator. To date, it is not known how chronic hepatitis C virus (HCV) infection affects the autonomic nervous system. In the present study, we compared cardiovagal autonomic function in patients with chronic HCV infection and healthy controls and examined the relation between autonomic function and serum levels of aminotransferases, HCV RNA, cryoglobulins, albumin and glucose. Autonomic function was assessed in 45 treatment-naïve patients with chronic HCV infection and in 40 healthy controls by determining spontaneous baroreflex sensitivity (BRS) and heart rate variability (HRV) indices. The R-R interval was determined by electrocardiogram recording; continuous radial artery pressure was monitored simultaneously by applanation tonometry. Laboratory analyses and quantitative polymerase chain reaction for serum HCV RNA level were performed by standard procedures. BRS and HRV time and frequency domain indices were lower in patients with HCV infection compared with healthy controls [7.1+/-3.4 vs. 11.5+/-6.5 ms/mmHg for BRS, 168.5+/-160.9 vs. 370.7+/-349.4 ms(2) for low-frequency HRV (mean+/-SD); P<0.01]. Multivariate analysis showed that autonomic dysfunction in HCV-infected patients correlated with elevated alanine aminotransferase levels, but was not associated with serum HCV RNA levels and cryoglobulins. Our results suggest that impaired autonomic function is caused by chronic HCV infection. Further studies are needed, however, to identify the underlying mechanisms.