Modulation Of Heart Rate Research Articles

A Community-Based Trial of Commercially Available Compression Tights in Patients With Postural Orthostatic Tachycardia Syndrome.

Compression garments reduce heart rate and symptoms in patients with postural orthostatic tachycardia syndrome in an acute laboratory setting. Patients taking medications controlling heart rate have less benefit from compression than those not on medications. The effectiveness of commercially available garments in a community-based setting, with and without medication use, is not known. The authors sought to evaluate commercially available compression tights in a community-based setting both with, and without, medications modulating heart rate, using a clinical trial with 2 before-after protocols conducted in a randomized crossover fashion. Participants (N=26) held medications during protocol #1 and took medications as normal during protocol #2. For each, participants completed 4, 10-minute active stand tests in the morning (AM) and afternoon (PM) with the garments on (ON) and off (OFF) (AM-OFF, AM-ON, PM-ON, and PM-OFF). Heart rate (Holter monitor) and symptoms (Vanderbilt Orthostatic Symptom Score [VOSS]) were measured for each standing test. Protocol #1: Standing heart rate was reduced (105 [99-116] beats/min vs 119 [105-130] beats/min; P< 0.001) and symptoms improved (P< 0.001), during AM-ON vs AM-OFF. Standing heart rate (P=0.04) and symptoms (P=0.004) increased when compression was removed after several hours. Protocol #2: Standing heart rate was reduced (84 [77-90] beats/min vs 89 [84-100] beats/min; P< 0.001), and symptoms improved (P=0.03), during AM-ON vs AM-OFF. Standing heart rate (P=0.02) and symptoms (P< 0.001) increased when compression was removed after several hours. Commercially available compression tights reduced heart rate and symptoms both acutely and after several hours of use. This additional benefit persisted whether concomitant medications were used. (Compression Garments in the Community With POTS [COM-COM-POTS]; NCT04881318).

Could piano music therapy alleviate high sinus rhythm in subjects with controlled hypertension?

Abstract Background/Introduction With a millenary tradition, music is rediscovered nowadays, as adjuvant therapy. The number of beats per minute (bpm) is the common factor of cardiology – representing heart rate (HR), and music – reprezentative for tempo. Purpose Our goal was the HR modulation in patients (pts) with moderate tachycardia using three piano kits: K1 – Adagio by Albinoni, K2 – Piano Concerto nr. 21 by Mozart, second part; and K3 – Liebestraum by Liszt. Methods During 1st January – 31st December 2023, we identified by ambulatory screening 288 pts adequate for our goal. As exclusion criterion, we considered any type of rhythm or conduction dysturbances. All selected pts were controlled with antihypertensive agents not altering HR, usually thiazide/thiazide-like diuretics and/or ACEis/ARBs. The study group consisted in 144 hypertensive pts controlled at least six months, without any other cardiac diseases. The control group consisted in 144 pts with normal cardiologic examination. Both groups were demographically balanced. The HR at admission was between 84 and 120 bpm, the pts being stratified in three bpm subcategories. All pts have done three visits consisting in: physical examination, ECG, lab markers, TTE for V1 at initiation and EoS at six months, and respectively, physical exam and ECG for V2 at 3 months. Results (in bpm): Inside the group with HR 84-96 treated with K1, the Controlled HTN group (CHG) and the Normal Cardiac group (NCG) alleviated HR from 85,8 +/- 12,6 to 82,6 +/- 12,2; and from 85,7 +/- 12,6 to 80,8 +/- 11,9, respectively. For pts inside the interval 97-108 treated with K1, the CHG group and the NCG alleviated HR from 94,3 +/- 14,1 to 90,9 +/- 13,7 and, respectively, from 94,4 +/- 14,1 to 89,7 +/- 13,6. In pts from HR spectrum 97-108 treated with K2, the CHG and the NCG alleviated HR from 98,4 +/- 14,6 to 95,7 +/- 14,1; and from 98,5 +/- 14,6 to 94,1 +/- 13,8; respectively. Inside the group with HR spectrum 109-120 treated with K1, the CHG and the NCG alleviated HR from 97,1 +/- 14,3 to 94,8 +/- 13,9; and, respectively, from 97,0 +/- 14,3 to 93,9 +/- 13,7. For pts inside the interval 109-120 treated with K2, the CHG and the NCG alleviated HR from 101,7 +/- 14,6 to 99,3 +/- 14,2; and from 101,8 +/- 14,6 to 97,3 +/- 14,1; respectively. In pts from HR spectrum 109-120 treated with K3, the CHG and the NCG alleviated HR from 106,1 +/- 14,7 to 103,8 +/- 14,6; and from 106,5 +/- 14,4 to 103,6 +/- 14,4; respectively. Conclusions The effect of piano music on HR seems favorable in controlled hypertensive pts without major comorbidities, probably by interfering the sympathetic vegetative nervous system. In this regard, it could be used as adjuvant in optimizing this cardiac parameter. However, a multicentered randomized clinical study will be needed.

Effect of Optimal Heart Rate on Left Ventricular Remodeling in Patients with Systolic Heart Failure Following Acute Coronary Syndrome.

The optimal therapeutic approach to facilitate reverse remodeling is desired in patients with systolic heart failure following acute coronary syndrome (ACS). The association between heart rate (HR) and reverse remodeling in this cohort has remained elusive.Patients with left ventricular ejection fraction (LVEF) < 50% who received echocardiography assessments following ACS were retrospectively included. Theoretically ideal HR was calculated using a previously established formula: 93 - 0.13 × (deceleration time [msec]). Impacts of HR on echocardiographic left ventricular (LV) reverse remodeling during the 2-year observational period were compared between 2 groups stratified by the HR difference between theoretically ideal and actual values: optimal HR group (HR difference ≤ 10 bpm) versus sub-optimal HR group (HR difference > 10 bpm).A total of 27 patients (median 72 years old, 23 males) were included. There were no significant differences in the baseline characteristics including maximum serum creatinine kinase level and the dose of beta-blocker between the 2 groups. LV ejection fraction increased significantly only in the optimal HR group at follow-up (from 42% to 54%; P = 0.001). The optimal HR group exhibited a more pronounced decrease in LV end-diastolic diameter (from 57 to 52 mm) compared to the sub-optimal HR group (from 58 to 56 mm).Optimal HR, which was calculated using a previously proposed formula, was associated with more substantial post-infarct LV reverse remodeling. The implications of aggressive HR modulation targeting theoretically ideal HR among those with systolic heart failure following ACS are the focus of our investigation here.

Effects of voluntary exercise and electrical muscle stimulation on reaction time in the Go/No-Go task.

Acute exercise improves cognitive performance. However, it remains unclear what triggers cognitive improvement. Electrical muscle stimulation (EMS) facilitates the examination of physiological changes derived from peripheral muscle contraction during exercise. Thus, we compared the effects of EMS and voluntary exercise at low- or moderate-intensity on reaction time (RT) in a cognitive task to understand the contribution of central and peripheral physiological factors to RT improvement. Twenty-four young, healthy male participants performed a Go/No-Go task before and after EMS/exercise. In the EMS condition, EMS was applied to the lower limb muscles. In the low-intensity exercise condition, the participants cycled an ergometer while maintaining their heart rate (HR) at the similar level during EMS. In the moderate-intensity exercise condition, exercise intensity corresponded to ratings of perceived exertion of 13/20. The natural log-transformed root mean square of successive differences between adjacent inter-beat (R-R) intervals (LnRMSSD), which predominantly reflects parasympathetic HR modulation, was calculated before and during EMS/exercise. RT improved following moderate-intensity exercise (p = 0.002, Cohen' d = 0.694), but not following EMS (p = 0.107, Cohen' d = 0.342) and low-intensity exercise (p = 0.076, Cohen' d = 0.380). Repeated measures correlation analysis revealed that RT was correlated with LnRMSSD (Rrm(23) = 0.599, p = 0.002) in the moderate-intensity exercise condition. These findings suggest that the amount of central neural activity and exercise pressor reflex may be crucial for RT improvement. RT improvement following moderate-intensity exercise may, at least partly, be associated with enhanced sympathetic nervous system activity.

Age as an Effect Modifier of the Effects of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) on Heart Rate Variability in Healthy Subjects.

Background: Evidence suggests that vagus nerve stimulation can modulate heart rate variability (HRV). However, there is a lack of mechanistic studies in healthy subjects assessing the effects of bilateral transcutaneous auricular vagus nerve stimulation (taVNS) on HRV. Our study aims to investigate how taVNS can influence the HRV response, including the influence of demographic variables in this response. Methods: Therefore, we conducted a randomized controlled study with 44 subjects, 22 allocated to active and 22 to sham taVNS. Results: Our results showed a significant difference between groups in the high-frequency (HF) metric. Active taVNS increased the HF metric significantly as compared to sham taVNS. Also, we found that age was a significant effect modifier of the relationship between taVNS and HF-HRV, as a larger increase in HF-HRV was seen in the older subjects. Importantly, there was a decrease in HF-HRV in the sham group. Conclusions: These findings suggest that younger subjects can adapt and maintain a constant level of HF-HRV regardless of the type of stimulation, but in the older subjects, only the active taVNS recipients were able to maintain and increase their HF-HRV. These results are important because they indicate that taVNS can enhance physiological regulation processes in response to external events.

Increased stress burden and electrodermal reactivity in bladder cancer patients in comparison to healthy controls

The purpose of our study was to assess specific physiological parameters associated with stress responses in bladder cancer (BCa) patients compared to healthy individuals. By examining the transition from a supine to a sitting position, representing a mild physiological load, we investigated the changes in autonomic nervous system (ANS) activity as reflected by alterations in these parameters, indicating shifts in ANS regulation, using non-linear heart rate variability (HRV) parameters (0V%, 2UV%, parasympathetic and sympathetic nervous system – PNS and SNS indices), modified heart rate acceleration (ACmod) and deceleration capacities (DCmod), heart rate (HR), electrodermal activity (EDA), and also their correlations with perceived stress score. Our findings showed that BCa patients (n = 38) exhibited elevated resting HR, heightened SNS index, and increased EDA compared to their healthy counterparts (n = 47), indicating a notable physiological stress burden. The 0V% parameter showed a positive association with the SNS index, ACmod, HR, and EDA parameters, while displaying a negative correlation with the PNS index, DCmod and 2UV%. These non-linear HRV parameters, such as 0V% and 2UV%, offer nuanced insights into the complexities of heartbeat dynamics and autonomic regulation. After the transition from supine to sitting positions, BCa patients displayed higher EDA responses, indicating heightened stress reactivity and ANS sensitivity. These physiological distinctions persisted even when we did not prove differences in the levels of perceived stress between the studied groups. In conclusion, our study emphasizes the significance of identifying cancer patients at risk of ANS dysregulation, paving the way for tailored stress management strategies.

Development of autonomic heart rate modulations during childhood and adolescence

Autonomic control of heart rate is well known in adult subjects, but limited data are available on the development of the heart rate control during childhood and adolescence. Continuous 12-lead electrocardiograms were recorded in 1045 healthy children and adolescents (550 females) aged 4 to 19 years during postural manoeuvres involving repeated 10-min supine, unsupported sitting, and unsupported standing positions. In each position, heart rate was measured, and heart rate variability indices were evaluated (SDNN, RMSSD, and high (HF) and low (LF) frequency components were obtained). Quasi-normalized HF frequency components were defined as qnHF = HF/(HF + LF). These measurements were, among others, related to age using linear regressions. In supine position, heart rate decreases per year of age were significant in both sexes but lower in females than in males. In standing position, these decreases per year of age were substantially lowered. RMSSD and qnHF indices were independent of age in supine position but significantly decreased with age in sitting and standing positions. Correspondingly, LF/HF proportions showed steep increases with age in sitting and standing positions but not in the supine position. The study suggests that baseline supine parasympathetic influence shows little developmental changes during childhood and adolescence but that in young children, sympathetic branch is less responsive to vagal influence. While vagal influences modulate cardiac periods in young and older children equally, they are less able to suppress the sympathetic influence in younger children.

Early detection of cardiac autonomic dysfunction using the respiratory sinus arrhythmia accentuation maneuver in patients with stage B1 of Chagas Disease

Introduction: The maneuver to accentuate respiratory sinus arrhythmia (RSA) demonstrates to be a convenient instrument to evaluate the autonomic modulation of individuals with chronic Chagas disease cardiomyopathy (CCC), even with medication influence, as T-cruzi causes an inflammatory process creating lesions in the cardiac nerve endings of patients affected by Chagas disease. Objective: To evaluate the autonomic modulation of heart rate (HR) at rest and during the respiratory sinus arrhythmia accentuation maneuver (RSA-M) in patients with CCC in stage B1. Methods: thirty-six individuals were evaluated, divided into the CCC group, composed of 18 patients with Chagas heart disease, and the control group, formed by 18 healthy individuals. Heart rate variability (HRV) was collected beat by beat using the electrocardiography system Wincardio USB, supine for 10 minutes, and during the RSA-M for 6 minutes. Results: We observed higher values of statistical significance in Control group for mean HR (p = 0.005), IRR (p = 0.007), and worse autonomic adjustments related to SD2 / SD1 (p = 0.001) concerning CCC group in a supine position. However, evaluating the RSA-M, we observed a statistical difference in the delta I-E (p = 0,039) and the E / I rate (p = 0.045) of the Control group in relation to the CCC group. Conclusion: Patients with CCC showed better cardiovascular condition and HR control compared to the group of healthy individuals at rest. However, when subjected to RSA-M, the results showed a reduction in vagal balance in the autonomic control of individuals with CCC. Keywords: respiration; heart rate; chagas cardiomyopathy; autonomic nervous system diseases.

Enhancing Vagal Tone, Modulating Heart Rate Variability with Auricular Acupressure at Point Zero: A Randomized Controlled Trial.

Point Zero located within the vagus nerve's auricular branch shows promise in addressing imbalances. This study aims to explore its effects on vagal activity using auricular acupressure (AA), measured through heart rate variability (HRV). This single-blinded randomized controlled trial involved 114 healthy volunteers randomly assigned to receive AA (AA group, n = 57) or sham-AA (SA group, n = 57) at Point Zero. The 30-minute procedure comprised six stages: T1 and T2 (pre-intervention), T3 to T5 (intervention), and T6 (post-intervention). Interventions involving 30-s acupoint pressure stimulations at T3 and T5. The HRV-measured outcomes included heart rate (HR), standard deviation of R-R intervals (SDNN), root mean square of successive RR interval differences (RMSSD), natural logarithm of low-frequency power (LnLF), and natural logarithm of high-frequency power (LnHF). In addition, respiratory rate (RR) was monitored for its stability. The AA group demonstrated a significant decrease in HR and increases in SDNN, RMSSD, and LnHF from stages T3 to T6 compared with T1 (baseline), notably prominent at T3 (median changes [25th; 75th percentiles]: -2 [-5; -1], 17.85 [9.65; 31.72], 4.9 [1.08; 10.65], 0.26 [0.00; 0.62], respectively) and T5 (-3 [-6; -1], 19.45 [10.6; 32.89], 6.17 [-0.17; 16.34], 0.40 [-0.14; 0.83], respectively), while the SA group did not. LnLF showed nonsignificant alterations, and RR remained stable in both groups. Despite minor HRV fluctuations, the AA group consistently displayed significantly higher changes in SDNN and RMSSD compared with the SA group from T3 onwards. HR remained unchanged at T6, and LnHF significantly differed only at T5. AA at Point Zero may promptly enhance vagal activity, evident in the modulation of HRV, notably pronounced with pressure stimulation, and can be sustained for at least 5 min. Further studies are needed to assess its long-term effectiveness and efficacy in preventing or treating patients.(Clinical Trial Registration: NCT05586698).

Neuro-cardiac-guided transcranial magnetic stimulation: Unveiling the modulatory effects of low-frequency and high-frequency stimulation on heart rate.

Transcranial magnetic stimulation (TMS) is pivotal in the field of major depressive disorder treatment. Due to its unsatisfied response rate, an increasing number of researchers have turned their attention towards optimizing TMS site localization. Since the influence of TMS in reducing heart rate (HR) offers insights into its regulatory impact on the autonomic nervous system, a novel approach, called neurocardiac-guided TMS (NCG-TMS), has been proposed to pinpoint the brain region eliciting the maximal individual reduction in HR as a personalized optimal stimulation target. The present study intends to systematically explore the effects of stimulation frequency, left and right hemispheres, stimulation positions, and individual differences on HR modulation using the NCG-TMS method. In experiment 1, low-frequency TMS was administered to 30 subjects, and it was found that low-frequency NCG-TMS significantly downregulated HR, with more significant effects in the right hemisphere than in the left hemisphere and the prefrontal cortex than in other brain areas. In experiment 2, high-frequency NCG-TMS stimulation was administered to 30 subjects, showing that high-frequency NCG-TMS also downregulated HR and had the greatest modulatory effect in the right prefrontal region. Simultaneously, both experiments revealed sizeable individual variability in the optimal stimulation site, which in turn validated the feasibility of the NCG-TMS method. In conclusion, the present experiments independently replicated the effect of NCG-TMS, provided an effect of high-/low-frequency TMS stimulation to downregulate HR, and identified a right lateralization of the HR modulation effect.

Importance of cardiac-synchronized vagus nerve stimulation parameters on the provoked chronotropic response for different levels of cardiac innervation.

The influence of vagus nerve stimulation (VNS) parameters on provoked cardiac effects in different levels of cardiac innervation is not well understood yet. This study examines the effects of VNS on heart rate (HR) modulation across a spectrum of cardiac innervation states, providing data for the potential optimization of VNS in cardiac therapies. Utilizing previously published data from VNS experiments on six sheep with intact innervation, and data of additional experiments in five rabbits post bilateral rostral vagotomy, and four isolated rabbit hearts with additionally removed sympathetic influences, the study explored the impact of diverse VNS parameters on HR. Significant differences in physiological threshold charges were identified across groups: 0.09 ± 0.06μC for intact, 0.20 ± 0.04μC for vagotomized, and 9.00 ± 0.75μC for isolated hearts. Charge was a key determinant of HR reduction across all innervation states, with diminishing correlations from intact (r = 0.7) to isolated hearts (r = 0.44). An inverse relationship was observed for the number of pulses, with its influence growing in conditions of reduced innervation (intact r = 0.11, isolated r = 0.37). Frequency and stimulation delay showed minimal correlations (r < 0.17) in all conditions. Our study highlights for the first time that VNS parameters, including stimulation intensity, pulse width, and pulse number, crucially modulate heart rate across different cardiac innervation states. Intensity and pulse width significantly influence heart rate in innervated states, while pulse number is key in denervated states. Frequency and delay have less impact impact across all innervation states. These findings suggest the importance of customizing VNS therapy based on innervation status, offering insights for optimizing cardiac neuromodulation.

Characterization of heart rate variability in end-stage renal disease patients after kidney transplantation with recurrence quantification analysis.

Heart rate variability (HRV) is a noninvasive approach to studying the autonomic modulation of heart rate in experimental settings, such as active standing sympathetic stimulation. It is known that patients with end-stage renal disease during active standing have few changes in HRV dynamics, which are improved after hemodialysis. However, it is unknown whether the response to active standing is recovered after definitive treatment with kidney transplantation. This work aims to assess the change in HRV dynamics in the supine position and active standing through time and frequency-based metrics, as well as recurrence plot quantitative analysis (RQA). We studied HRV dynamics by obtaining 5-minute electrocardiographic recordings from kidney transplant recipients who underwent an active standing test. The mean duration of heartbeats and their standard deviation diminished in active standing, compared with the supine position. Also, the low-frequency component of HRV and the presence of diagonal and vertical structures in RQA were predominant. A larger estimated glomerular filtration rate was significantly correlated with broader HRV in the supine position and during active standing. The narrower HRV during active standing may indicate a sympathetic response to external stimuli, which is expected in a functional cardiovascular system, and may be influenced by renal function.

Accelerated physiologic pacing in patients with heart failure with preserved ejection fraction: An argument in support of therapeutic heart rate modulation

Accelerated physiologic pacing in patients with heart failure with preserved ejection fraction: An argument in support of therapeutic heart rate modulation

Impact of anesthesia on micromagnetic stimulation (μMS) of the vagus nerve

To treat diseases associated with vagal nerve control of peripheral organs, it is necessary to selectively activate efferent and afferent fibers in the vagus. As a result of the nerve’s complex anatomy, fiber-specific activation proves challenging. Spatially selective neuromodulation using micromagnetic stimulation(μMS) is showing incredible promise. This neuromodulation technique uses microcoils(μcoils) to generate magnetic fields by powering them with a time-varying current. Following the principles of Faraday’s law of induction, a highly directional electric field is induced in the nerve from the magnetic field. In this study on rodent cervical vagus, a solenoidal μcoil was oriented at an angle to left and right branches of the nerve. The aim of this study was to measure changes in the mean arterial pressure (MAP) and heart rate (HR) following μMS of the vagus. The μcoils were powered by a single-cycle sinusoidal current varying in pulse widths(PW = 100, 500, and 1000 μsec) at a frequency of 20 Hz. Under the influence of isoflurane, μMS of the left vagus at 1000 μsec PW led to an average drop in MAP of 16.75 mmHg(n = 7). In contrast, μMS of the right vagus under isoflurane resulted in an average drop of 11.93 mmHg in the MAP(n = 7). Surprisingly, there were no changes in HR to either right or left vagal μMS suggesting the drop in MAP associated with vagus μMS was the result of stimulation of afferent, but not efferent fibers. In urethane anesthetized rats, no changes in either MAP or HR were observed upon μMS of the right or left vagus(n = 3). These findings suggest the choice of anesthesia plays a key role in determining the efficacy of μMS on the vagal nerve. Absence of HR modulation upon μMS could offer alternative treatment options using VNS with fewer heart-related side-effects.

Effects of Yoga and Mindfulness Meditation on Stress-Related Variables: A Randomized Controlled Trial.

Stressful situations lead to change in or damage to the central nervous system, the hypothalamic-pituitary-adrenal axis, and autonomic function. Techniques for reducing stress such as yoga and mindfulness meditation have been reported to improve emotional regulation and mindfulness skill, as well as stress response. Mindfulness skill relies on intense focus to quiet the mind and bring concentration to the present moment. The present study was a randomized control trial to investigate the effects of an 8-week training program (three 45-minute sessions/week, one session with an instructor and two sessions as home practice) in mindfulness meditation or in yoga on stress and related variables in healthy people. Forty-four healthy participants were randomly allocated to one of three groups: a mindfulness group (n = 16), a yoga group (n = 13), and a control group (n = 15). The yoga training significantly modified heart rate variability, contributing to decreased relative power of the low-frequency band; the relative power of the high-frequency band increased after training. The mindfulness meditation training significantly improved mindfulness skill and concentration performance. In the present study, yoga was associated with increased heart rate variability and mindfulness meditation was associated with an increase in mindfulness skill and concentration performance.

Respiratory modulation of the heart rate: A potential biomarker of cardiorespiratory function in human

In recent decade, wearable digital devices have shown potentials for the discovery of novel biomarkers of humans’ physiology and behavior. Heart rate (HR) and respiration rate (RR) are most crucial bio-signals in humans’ digital phenotyping research. HR is a continuous and non-invasive proxy to autonomic nervous system and ample evidence pinpoints the critical role of respiratory modulation of cardiac function. In the present study, we recorded longitudinal (7 days, 4.63 ± 1.52) HR and RR of 89 freely behaving human subjects (Female: 39, age 57.28 ± 5.67, Male: 50, age 58.48 ± 6.32) and analyzed their dynamics using linear models and information theoretic measures. While HR’s linear and nonlinear characteristics were expressed within the plane of the HR–RR directed flow of information (HR→RR – RR→HR), their dynamics were determined by its RR→HR axis. More importantly, RR→HR quantified the effect of alcohol consumption on individuals’ cardiorespiratory function independent of their consumed amount of alcohol, thereby signifying the presence of this habit in their daily life activities. The present findings provided evidence for the critical role of the respiratory modulation of HR, which was previously only studied in non-human animals. These results can contribute to humans’ phenotyping research by presenting RR→HR as a digital diagnosis/prognosis marker of humans’ cardiorespiratory pathology.

The incubation environment does not explain significant variation in heart rate plasticity among avian embryos.

The conditions an organism experiences during development can modify how they plastically respond to short-term changes in their environment later in life. This can be adaptive because the optimal average trait value and the optimal plastic change in trait value in response to the environment may differ across different environments. For example, early developmental temperatures can adaptively modify how reptiles, fish and invertebrates metabolically respond to temperature. However, whether individuals within populations respond differently (a prerequisite to adaptive evolution), and whether this occurs in birds, which are only ectothermic for part of their life cycle, is not known. We experimentally tested these possibilities by artificially incubating the embryos of Pekin ducks (Anas platyrhynchos domesticus) at constant or variable temperatures. We measured their consequent heart rate reaction norms to short-term changes in egg temperature and tracked their growth. Contrary to expectations, the early thermal environment did not modify heart rate reaction norms, but regardless, these reaction norms differed among individuals. Embryos with higher average heart rates were smaller upon hatching, but heart rate reaction norms did not predict subsequent growth. Our data also suggests that the thermal environment may affect both the variance in heart rate reaction norms and their covariance with growth. Thus, individual avian embryos can vary in their plasticity to temperature, and in contrast to fully ectothermic taxa, the early thermal environment does not explain this variance. Because among-individual variation is one precondition to adaptive evolution, the factors that do contribute to such variability may be important.

Clinical Implications of Ivabradine in the Contemporary Era.

Ivabradine is a recently introduced inhibitor of the If ion channel, which exhibits the capacity to reduce heart rate while preserving hemodynamic stability. At present, ivabradine finds its clinical indication in patients suffering from heart failure with reduced ejection fraction and maintaining a relative sinus rhythm refractory to beta-blockers. To optimize heart rate control, it is recommended to pursue an aggressive up-titration of ivabradine. This approach may ameliorate tachycardia-induced hypotension by incrementally enhancing cardiac output and allow further up-titration of agents aimed at ameliorating heart failure, such as beta-blockers. Both the modulation of heart rate itself and the up-titration of agents targeting heart failure lead to cardiac reverse remodeling, consequently culminating in a subsequent reduction in mortality and morbidity. A novel overlap theory that our team proposed recently has emerged in recent times. Under trans-mitral Doppler echocardiography, the E-wave and A-wave closely juxtapose one another without any overlapping at the optimal heart rate. Employing echocardiography-guided ivabradine for heart-rate modulation to minimize the overlap between the E-wave and A-wave appears to confer substantial benefits to patients with heart failure. This approach facilitates superior cardiac reverse remodeling and yields more favorable clinical outcomes when compared to those patients who do not receive echocardiography-guided care. The next pertinent issue revolves around the potential expansion of ivabradine's clinical indications to encompass a broader spectrum of diseases. It is imperative to acknowledge that ivabradine may not yield clinically significant benefits in patients afflicted by heart failure with preserved ejection fraction, acute heart failure, sepsis, or stable angina. An important fact yet to be explored is the clinical applicability of ivabradine in patients with atrial fibrillation, a concern that beckons future investigation. In this review, the concept of overlap theory it introduced, along with its application to expand the indication of ivabradine and the overlap theory-guided optimal ivabradine therapy.

Osteopathic Cranial Manipulation and its Possible Application in Managing Hypertension for the Optimization of Care

Context: Approximately 50% of US adults suffer from hypertension, with over 75% inadequately controlled. The baroreceptor reflex elicits vagal stimulation, reducing heart rate and blood pressure. Non-invasive osteopathic cranial manipulation (OCM), including occipito-atlantal (OA) release, may enhance vagal tone. This literature review examines the potential efficacy of OCM in optimizing hypertension management by augmenting vagal tone and subsequently reducing blood pressure. Objective: To determine whether osteopathic cranial manipulation (OCM) may be utilized for blood pressure reduction and hypertension management via vagal nerve stimulation affecting the baroreceptor reflex. Specifically, we aim to investigate the effects occipito-atlantal (OA) release has on vagal tone and determine whether it has reasonable applications within hypertensive conditions. Methods: Our group searched for credible literature sources on Still OneSearch, DynaMed, Google Scholar, PubMed, MEDLINE, and National Institutes of Health (NIH) online databases as well as the following journals: Frontiers in Neuroscience, Journal of Alternative and Complementary Medicine, and Medicines. The search strategy included keywords or a combination of keywords such as “hypertension or high blood pressure”, “baroreceptor reflex”, “vagal nerve stimulation”, and “osteopathy or osteopathic manual therapy or OMT or manual therapy or osteopathic medicine or osteopathic treatment” to discover related articles. Filters for peer reviewed sources with access to full text and publication dates between 2010 - 2023 were applied to our search, narrowing the results to only the most up-to-date information. Once studies of interest were selected, the articles were read and analyzed with pertinent components referenced throughout our literature review in accordance with AMA citation format. Altogether, this project demonstrates osteopathic significance because it emphasizes the value of osteopathic cranial manipulation (OCM), spreads awareness of Sutherland’s philosophies, and underscores the possibility of OCM applications in the treatment of hypertension. Furthermore, it describes how OCM can be used in combination with or as a safer alternative to managing hypertensive conditions, thus creating more options for providing quality healthcare. Results: This literature review sought to examine the potential efficacy of HTN management through the utilization of osteopathic cranial manipulation. In the clinical and preclinical studies of vagus nerve stimulation (VNS) therapy, it was found that a 4-week-long VNS therapy significantly decreased mean arterial pressure and the number of arrhythmic episodes in rats with salt-induced hypertension, with a potential side effect being bradycardia due to asystole. In theory, by initiating manual biomechanical alignment in the OA joint would improve vagus nerve function and thus increase parasympathetic function to the heart to reduce atrial contraction, comparable to VNS. A study examining 19 healthy, young adults who underwent cervical OMT and had their heart rates measured pre- and post-electrocardiography, revealed moderate enhancement of parasympathetic HR control. In another study of 63 subjects with hypertension who were treated with OMT for 1 year, it was found that their systolic blood pressure improved significantly. In a randomized controlled study, a combination of kneading and stretching of soft tissues and suboccipital decompression, there is an increase of 15% of parasympathetic modulation of heart rate with p=0.02. Conclusion: Research agrees that the instigation of parasympathetic activity through vagal nerve stimulation adjusts heart rate in the response to baroreceptors that detect arterial pressure changes within the heart. Giles et al demonstrated a positive relationship between the effects of OMT and acute heart rate variability. However, the relationship between heart rate and vagal activity is not linear, and has been previously difficult to clearly denote. Overall, this literature review demonstrates the significant impact hypertension has on society and the need for alternative treatments. In research conducted by Giles et al, OMT was proven to have an effect on heart rate variability in health individuals and although the research was not conducted on patients with somatic dysfunction, the data suggests that the effect on heart rate via OMT is measurable and definitive. This lends to a promising advancement in the relationship between OMT and heart rate in a diseased population. Assessment of this change in the frequency domain of autonomic control suggests necessary evaluation of the shift in sympathetic to parasympathetic states within chronic HTN patients. In evaluation of current research, it is not possible to draw a definitive conclusion about the effectiveness of OCM on the management of HTN. Future research should be conducted in the evaluation of OCM and the specific types of techniques that offer the greatest effect on both heart rate and blood pressure. Ideally these projects would determine the effectiveness of OCM through a dedicated, well-designed, controlled and blinded outcome study for the evaluation of statistically significant results. The data that would be extracted from these future studies could have profound impacts on the integration of OMT into the scheme of hypertension management and inform policy changes to enable it as a viable tool for treatment.

Hyperpolarization-activated cyclic nucleotide-gated channel inhibitor in myocardial infarction: Potential benefits beyond heart rate modulation.

Myocardial infarction (MI) and its associated complications including ventricular arrhythmias and heart failure are responsible for a significant incidence of morbidity and mortality worldwide. The ensuing cardiomyocyte loss results in neurohormone-driven cardiac remodeling, which leads to chronic heart failure in MI survivors. Ivabradine is a heart rate modulation agent currently used in treatment of chronic heart failure with reduced ejection fraction. The canonical target of ivabradine is the hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in cardiac pacemaker cells. However, in post-MI hearts, HCN can also be expressed ectopically in non-pacemaker cardiomyocytes. There is an accumulation of intriguing evidence to suggest that ivabradine also possesses cardioprotective effects that are independent of heart rate reduction. This review aims to summarize and discuss the reported cardioprotective mechanisms of ivabradine beyond heart rate modulation in myocardial infarction through various molecular mechanisms including the prevention of reactive oxygen species-induced mitochondrial damage, improvement of autophagy system, modulation of intracellular calcium cycling, modification of ventricular electrophysiology, and regulation of matrix metalloproteinases.