Autonomic Modulation of Cardiac Arrhythmias: Methods to Assess Treatment and Outcomes.
Ontology highlight
ABSTRACT:
SUBMITTER: Stavrakis S
PROVIDER: S-EPMC7370838 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundBilateral cardiac sympathetic denervation (BCSD) is an effective therapy for ventricular arrhythmias (VAs) in cardiomyopathies (CMPs). After BCSD, residual autonomic nervous system (ANS) function is unknown.ObjectiveThe purpose of this study was to assess ANS responses in patients with CMP before and after BCSD as compared with demographically matched healthy controls.MethodsPatients with CMP undergoing BCSD and matched healthy controls were recruited. Noninvasive measures-finger cuff beat-to-beat blood pressure (BP), electrocardiography, palmar electrodermal activity (EDA), and finger pulse volume (FPV)-were obtained at rest and during autonomic stressors-posture change, handgrip, and mental stress. Maximal as well as specific responses to stressors were compared.ResultsEighteen patients with CMP (mean age 54 ± 14 years; 16 men, 89%; left ventricular ejection fraction 36% ± 14%) with refractory VAs and 8 matched healthy controls were studied; 9 patients with CMP underwent testing before and after (median 28 days) BCSD, with comparable ongoing medication. Before BCSD, patients with CMP (n = 13) had lower resting systolic BP and FPV than did healthy controls (P < .01). Maximal FPV and systolic BP reflex responses, expressed as percent change were similar, while diastolic BP, mean BP, and EDA responses were blunted. After BCSD, resting measurements were unchanged relative to presurgical baseline (n = 9). EDA responses to stressors were abolished, confirming BCSD, while maximal FPV and BP responses were preserved. Diastolic BP, mean BP, and FPV responses to orthostatic challenge pointed toward a better tolerance of active standing after BCSD as compared with before. Responses to other stressors remained unchanged.ConclusionPatients with CMP and refractory VAs on optimal medical therapy have detectable but blunted adrenergic responses, which are not disrupted by BCSD.
| S-EPMC7395890 | biostudies-literature
Project description:Background and purposeIncrease in high-frequency beat-to-beat heart rate oscillations by torsadogenic hERG blockers appears to be associated with signs of parasympathetic and sympathetic co-activation which cannot be assessed directly using classic methods of heart rate variability analysis. The present work aimed to find a translational model that would allow this particular state of the autonomic control of heart rate to be assessed.Experimental approachHigh-frequency heart rate and heart period oscillations were analysed within discrete 10 s intervals in a cohort of 200 healthy human subjects. Results were compared to data collected in non-human primates and beagle dogs during pharmacological challenges and torsadogenic hERG blockers exposure, in 127 genotyped LQT1 patients on/off β-blocker treatment and in subgroups of smoking and non-smoking subjects.Key resultsThree states of autonomic modulation, S1 (parasympathetic predominance) to S3 (reciprocal parasympathetic withdrawal/sympathetic activation), were differentiated to build a new model of heart rate variability referred to as high-frequency autonomic modulation. The S2 state corresponded to a specific state during which both parasympathetic and sympathetic systems were coexisting or co-activated. S2 oscillations were proportionally increased by torsadogenic hERG-blocking drugs, whereas smoking caused an increase in S3 oscillations.Conclusions and implicationsThe combined analysis of the magnitude of high-frequency heart rate and high-frequency heart period oscillations allows a refined assessment of heart rate autonomic modulation applicable to long-term ECG recordings and offers new approaches to assessment of the risk of sudden death both in terms of underlying mechanisms and sensitivity.
| S-EPMC6031873 | biostudies-literature
Project description:The purpose of this investigational study was to assess the effects of melatonin replacement therapy on cardiac autonomic modulation in pinealectomized patients. This was an open-label, single-arm, single-center, proof-of-concept study consisting of a screening period, a 3-month treatment period with melatonin (3 mg/day), and a 6-month washout period. The cardiac autonomic function was determined through heart rate variability (HRV) measures during polysomnography. Pinealectomized patients (n = 5) with confirmed absence of melatonin were included in this study. Melatonin treatment increased vagal-dominated HRV indices including root mean square of the successive R-R interval differences (RMSSD) (39.7 ms, 95% CI 2.0-77.4, p = 0.04), percentage of successive R-R intervals that differ by more than 50 ms (pNN50) (17.1%, 95% CI 9.1-25.1, p = 0.003), absolute power of the high-frequency band (HF power) (1,390 ms2, 95% CI 511.9-2,267, p = 0.01), and sympathetic HRV indices like standard deviation of normal R-R wave interval (SDNN) (57.6 ms, 95% CI 15.2-100.0, p = 0.02), and absolute power of the low-frequency band (LF power) (4,592 ms2, 95% CI 895.6-8,288, p = 0.03). These HRV indices returned to pretreatment values when melatonin treatment was discontinued. The HRV entropy-based regularity parameters were not altered in this study, suggesting that there were no significant alterations of the REM-NREM ratios between the time stages of the study. These data show that 3 months of melatonin treatment may induce an improvement in cardiac autonomic modulation in melatonin-non-proficient patients. ClinicalTrials.gov Identifier: NCT03885258.
| S-EPMC7213221 | biostudies-literature
Project description:Neuronal modulation of the sinoatrial node (SAN) plays a crucial role in the initiation and maintenance of atrial arrhythmias (AF), although the exact mechanisms remain unclear. We used a computer model of a rabbit right atrium (RA) with a heterogeneous SAN and detailed ionic current descriptions for atrial and SAN myocytes to explore reentry initiation associated with autonomic activity. Heterogeneous acetylcholine (ACh)-dependent ionic responses along with L-type Ca current (I(Ca,L)) upregulation were incorporated in the SAN only. During control, activation was typical with the leading pacemaker site located close to the superior vena cava or the intercaval region. With cholinergic stimulation, activation patterns frequently included caudal shifts of the leading pacemaker site and occasional double breakouts. The model became increasingly arrhythmogenic for the ACh concentration >20 nM and for large I(Ca,L) conductance. Reentries obtained included counterclockwise rotors in the free wall, clockwise reentry circulating between the SAN and free wall, and typical flutter. The SAN was the cause of reentry with a common leading sequence of events: a bradycardic beat with shifting in the caudal direction, followed by a premature beat or unidirectional block within the SAN. Electrotonic loading, and not just overdrive pacing, squelches competing pacemaker sites in the SAN. Cholinergic stimulation concomitant with I(Ca,L) upregulation shifts leading pacemaker site and can lead to reentry. A heterogeneous response to autonomic innervation, a large myocardial load, and an extensive SAN in the intercaval region are required for neurally induced SAN-triggered reentry.
| S-EPMC3774554 | biostudies-literature
Project description:Obesity leads to an imbalance in the autonomic nervous system, especially in increased sympathetic modulation and decreased vagal tone, and some anthropometric, metabolic, and lifestyle variables may increase the risk of developing cardiovascular disease. Objective. To analyze the association between cardiovascular autonomic modulation and biochemical and anthropometric markers, food intake, and physical activity level in severely obese individuals. Methodology. The present study is a cutout of a randomized clinical trial "Effect of nutritional intervention and olive oil in severe obesity" (DieTBra Trial), where the baseline data were analyzed. Anthropometric data, biochemical exams, heart rate variability (HRV), accelerometry, and 24?h recall (R24H) of obese patients (body mass index BMI ?35?kg/m2) were collected. Results. 64 obese patients were analyzed, with a mean age of 39.10?±?7.74 years (27 to 58 years). By HRV analysis, in the frequency domain, the obese had a higher predominance of sympathetic autonomic modulation (low frequency (LF) 56.44?±?20.31?nu) and lower parasympathetic modulation (high frequency (HF) 42.52?±?19.18?nu). A negative association was observed between the variables Homeostasis Evaluation Model (HOMA-IR) and HF (p = 0.049). In the physical activity analysis, there was a negative association between moderate to vigorous physical activity and the sympathetic component (p = 0.043), and for sedentary time (ST), there was a negative association with HF (p = 0.049) and LF/HF (p = 0.036) and a positive association with LF (p = 0.014). For multiple linear regression, waist circumference (WC) and HOMA-IR values were negatively associated with HF (??=?-0.685, p = 0.010; ??=?-14.989, p = 0.010; respectively). HOMA-IR (??=?0.141, p = 0.003) and the percentage of lipids ingested (??=?-0.030, p = 0.043) were negatively associated with LF/HF. Conclusion. Among the cardiovascular risk variables studied, insulin resistance and central adiposity showed the greatest influence on cardiac autonomic modulation of obese, increasing the risk for cardiovascular disease.
| S-EPMC7152942 | biostudies-literature
Project description:Background In patients with end-stage kidney disease, sudden cardiac death is more frequent after a long interdialytic interval, within 6 hours after the end of a hemodialysis session. We hypothesized that the occurrence of paroxysmal arrhythmias is associated with changes in heart rate and heart rate variability in different phases of hemodialysis. Methods and Results We conducted a prospective ancillary study of the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease cohort. Continuous ECG monitoring was performed using an ECG patch, and short-term heart rate variability was measured for 3 minutes every hour (by root mean square of the successive normal-to-normal intervals, spectral analysis, Poincaré plot, and entropy), up to 300 hours. Out of enrolled participants (n=28; age 54±13 years; 57% men; 96% black; 33% with a history of cardiovascular disease; left ventricular ejection fraction 70±9%), arrhythmias were detected in 13 (46%). Nonsustained ventricular tachycardia occurred more frequently during/posthemodialysis than pre-/between hemodialysis (63% versus 37%, P=0.015). In adjusted for cardiovascular disease time-series analysis, nonsustained ventricular tachycardia was preceded by a sudden heart rate increase (by 11.2 [95% CI 10.1-12.3] beats per minute; P<0.0001). During every-other-day dialysis, root mean square of the successive normal-to-normal intervals had a significant circadian pattern (Mesor 10.6 [ 95% CI 0.9-11.2] ms; amplitude 1.5 [95% CI 1.0-3.1] ms; peak at 02:01 [95% CI 20:22-03:16] am; P<0.0001), which was replaced by a steady worsening on the second day without dialysis (root mean square of the successive normal-to-normal intervals -1.41 [95% CI -1.67 to -1.15] ms/24 h; P<0.0001). Conclusions Sudden increase in heart rate during/posthemodialysis is associated with nonsustained ventricular tachycardia. Every-other-day hemodialysis preserves circadian rhythm, but a second day without dialysis is characterized by parasympathetic withdrawal.
| S-EPMC6806026 | biostudies-literature
Project description:Arrhythmias are critical contributors to cardiovascular morbidity and mortality. Therapies are mainly symptomatic and often insufficient, emphasizing the need for basic research to unveil the mechanisms underlying arrhythmias and to enable better and ideally causal therapies. In translational approaches, mice are commonly used to study arrhythmia mechanisms in vivo. Experimental electrophysiology studies in mice are performed under anesthesia with medetomidine/midazolam/fentanyl (MMF) and isoflurane/fentanyl (IF) as commonly used regimens. Despite evidence of adverse effects of individual components on cardiac function, few data are available regarding the specific effects of these regimens on cardiac electrophysiology in mice. Here we present a study investigating the effects of MMF and IF narcosis on cardiac electrophysiology in vivo in C57BL/6N wild-type mice. Telemetry transmitters were implanted in a group of mice, which served as controls for baseline parameters without narcosis. In two other groups of mice, electrocardiogram and invasive electrophysiology studies were performed under narcosis (with either MMF or IF). Basic electrocardiogram parameters, heart rate variability parameters, sinus node and atrioventricular node function, and susceptibility to arrhythmias were assessed. Experimental data suggest a remarkable influence of MMF on cardiac electrophysiology compared with IF and awake animals. While IF only moderately reduced heart rate, MMF led to significant bradycardia, spontaneous arrhythmias, heart rate variability alterations as well as sinus and AV node dysfunction, and increased inducibility of ventricular arrhythmias. On the basis of these observed effects, we suggest avoiding MMF in mice, specifically when studying cardiac electrophysiology, but also whenever a regular heartbeat is required for reliable results, such as in heart failure or imaging research.
| S-EPMC10063441 | biostudies-literature
Project description:Fingolimod is an oral sphingosine-1-phospate (S1P) receptor modulator for the treatment of relapsing-remitting multiple sclerosis (RRMS). In addition to therapeutic effects on lymphoid and neural tissue, fingolimod influences cardiovascular system by specific S1P-receptor modulation. The effects of S1P-receptor modulation on the endogenous circadian pattern of cardiac autonomic regulation (CAR), however, are not known. We examined the effects of fingolimod on the circadian pattern of CAR Ambulatory 24-h ECG recordings were undertaken in 27 RRMS patients before fingolimod (baseline), at the day of fingolimod initiation (1D) and after 3 months of fingolimod treatment (3M). The mean time between two consecutive R-peaks (RR-interval) and mean values for measures of heart rate variability (HRV) in time- and frequency domain were calculated from ECG recording at daytime and nighttime. The mean night:day-ratio of RR-interval was 1.23 ± 0.12 at baseline, decreased temporarily at 1D (1.16 ± 0.12; P < 0.01) and was higher at 3M (1.32 ± 0.11; P < 0.001) than at baseline. The night:day-ratio of HRV parameters reflecting parasympathetic cardiac regulation (pNN50, rMSSD, HFnu) decreased at 1D but recovered back to baseline at 3M (P < 0.05 for all). On the other hand, the night:day-ratio of TP, a parameter reflecting overall HRV gradually decreased and was lower at 3M than at baseline (P < 0.05). Our findings suggest that physiological relation between the circadian pattern of RR-interval and overall HRV as well as parasympathetic cardiac regulation becomes uncoupled during fingolimod treatment. In addition, fingolimod shifts the circadian equilibrium of CAR toward greater daytime dominance of overall HRV Accordingly, S1P-receptor modulation influences circadian pattern of CAR.
| S-EPMC5027338 | biostudies-literature
Project description:The nuance of autonomic cardiac control has been studied for more than 400 years, yet little is understood. This review aimed to provide a comprehensive overview of the current understanding, clinical implications, and ongoing studies of cardiac sympathetic modulation and its anti-ventricular arrhythmias' therapeutic potential. Molecular-level studies and clinical studies were reviewed to elucidate the gaps in knowledge and the possible future directions for these strategies to be translated into the clinical setting. Imbalanced sympathoexcitation and parasympathetic withdrawal destabilize cardiac electrophysiology and confer the development of ventricular arrhythmias. Therefore, the current strategy for rebalancing the autonomic system includes attenuating sympathoexcitation and increasing vagal tone. Multilevel targets of the cardiac neuraxis exist, and some have emerged as promising antiarrhythmic strategies. These interventions include pharmacological blockade, permanent cardiac sympathetic denervation, temporal cardiac sympathetic denervation, etc. The gold standard approach, however, has not been known. Although neuromodulatory strategies have been shown to be highly effective in several acute animal studies with very promising results, the individual and interspecies variation between human autonomic systems limits the progress in this young field. There is, however, still much room to refine the current neuromodulation therapy to meet the unmet need for life-threatening ventricular arrhythmias.
| S-EPMC10221179 | biostudies-literature
Project description:Particulate matter < 2.5 μm (PM2.5) exposure is associated with increased arrhythmia events and cardiovascular mortality, but the detailed mechanism remained elusive. In the current study, we aimed to investigate the autonomic alterations in a rodent model after acute exposure to PM2.5. Twelve male WKY rats were randomized to control and PM2.5 groups. All were treated with 2 exposures of oropharyngeal aerosol inhalations (1 μg PM2.5 per gram of body weight in 100 μL normal saline for the PM2.5 group) separately by 7 days. Polysomnography and electrocardiography were surgically installed 7 days before oropharyngeal inhalation and monitored for 7 days after each inhalation. Physiologic monitors were used to define active waking (AW), quiet sleep (QS), and paradoxical sleep (PS). Autonomic regulations were measured by heart rate variability (HRV). The protein expression of ventricular tissue of the 2 groups was compared at the end of the experiment. In sleep pattern analysis, QS interruption of the PM2.5 group was significantly higher than the control group (0.52 ± 0.13 events/min, 0.35 ± 0.10 events/min, p = 0.002). In HRV analysis, the LF/HF was significantly higher for the PM2.5 group than the control group (1.15 ± 0.16, 0.64± 0.30, p = 0.003), largely driven by LF/HF increase during the QS phase. Ionic channel protein expression from Western blots showed that the PM2.5 group had significantly lower L-type calcium channel and higher SERCA2 and rectifier potassium channel expressions than the control group, respectively. Our results showed that acute PM2.5 exposure leads to interruption of QS, sympathetic activation, and recruitment of compensatory calcium handling proteins. The autonomic and calcium dysregulations developed after PM 2.5 exposure may explain the risk of sleep disturbance and sleep-related arrhythmia.
| S-EPMC10520066 | biostudies-literature