Cardiac Autonomic Tone Research Articles

Slow breathing exercise improves cardiac autonomic tone in hypothyroid patients: a frequency domain analysis of HRV

Background: Hypothyroidism is associated with autonomic dysfunction and oxidative stress. Slow breathing exercise (SBE), a yoga-based relaxation technique, improves cardiac autonomic nerve function by changing sympathetic or parasympathetic activity. Objective: To assess the effect of SBEon cardiac autonomic tone and in hypothyroid patients. Methods: This non randomized controlled trial was conducted on 50 newly diagnosed drug naive female hypothyroid patients (18-45 years of age)recruited from the outpatient department of the Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University,(BSMMU), Shahbag, Dhaka. Twenty five apparently healthy female subjects formed control group. . Among the 50 hypothyroid patients, 25 were consecutively assigned with SBE for 90 days (Group SBE) and the remaining 25 patients were without SBE and followed up after 90 days (Group NSBE). Both groups of patients received treatment with thyroid hormone replacement during their follow up period. Control group did not perform SBE or any other exercise. Data were recorded at baseline(Day 0) and after 90 days in all the subjects. Based on data recording period SBE group was designated as SBE0(at day 0 or pre intervention)and SBE90(at day 90 or post intervention). Similarly, NSBE0(day 0) and NSBE90 (day 90) and control group was also designated as control0 (day 0) and control90 (day 90).Resting cardic autonomic tonic activity was assessed by frequency domain analysis of Heart Rate Variability(HRV). HRV data were recorded by a digital data acquisition device Power Lab, AD Instrument Australia. Data were expressed as mean±SD. For statistical analysis, ANOVA followed by post hoc Bonferroni test and paired sample “t” test were done. Results: At baseline i.e. at day 0 before follow up, diastolic blood pressure (DBP) (p<0.05), low frequency in normalized unit (LF norm) (p<0.001), low frequency/high frequency ratio (LF/HF) (p<0.001) were significantly higher and total power (TP) (p<0.001), low frequency power (LF power) (p<0.01), high frequency power (HF power) (p<0.001), high frequency power in normalized unit (HF norm) (p<0.001) were significantly lower in hypothyroid patients (group SBE0and NSBE0 ) compared to healthy control (group control0). After 90 days of intervention with SBE, SBP, DBP, LF norm, LF/HF ratio decreased significantly and TP, HF power, HF norm increased significantly in group SBE90 compared to SBE0. Whereas, in group NSBE90, after 90 days of follow up, LF norm, LF/HF ratio decreased significantly and HF power, HF norm increased significantly compared to NSBE0. Again, after 90 days of follow up/SBEHF norm were significantly higher and LF norm, LF/HF ratio were significantly lower in SBE90 compared to NSBE90. In addition, significant difference was present in all these parameters between NSBE90 and control90. Also, after 90 days of SBELF norm, HF norm and LF/HF ratio was not significantly different from control. Conclusions: Based on these results, it can be concluded that autonomic dysfunction characterized by reduced vagal tone and sympathetic hyperactivity occurred in drug naïve hypothyroid patients. In addition, thyroid hormone replacement therapy improved autonomic dysfunction by increasing parasympathetic and decreasing sympathetic tonic activity. Moreover, SBE caused further improvement of autonomic dysfunction and could restore sympathovagal balance to its normal state in these patients. J Bangladesh Soc Physiol 2023;18(1): 9-18

Chronic acetylcholinesterase inhibition reduces the effects of physical training on ventricular contractility and coronary bed reactivity in hypertensive rats

Systemic arterial hypertension is accompanied by autonomic impairments that, if not contained, promotes cardiac functional and morphological damages. Pyridostigmine bromide (PYR) treatment results in positive effects on autonomic control and beneficial cardiac remodeling. These findings were also observed after aerobic physical training (APT). However, little is known about PYR effects on left ventricular contractility, mainly when it is combined with APT. We aimed to investigate the effects of chronic acetylcholinesterase inhibition on cardiac autonomic tone balance, coronary bed reactivity, and left ventricular contractility in spontaneously hypertensive rats (SHR) submitted to APT. Male SHR (18 weeks) were divided into two groups (N = 16): untrained and submitted to APT for 14 weeks (18th to 32nd week). Half of each group was treated with PYR (15 mg/kg/day) for two weeks (31st to 32nd week). The experimental protocol consisted of recording hemodynamic parameters, double autonomic blockade with atropine and propranolol, and assessment of coronary bed reactivity and ventricular contractility in isolated hearts using the Langendorff technique. PYR and APT reduced blood pressure, heart rate, and sympathetic influence on the heart. The Langendorff technique showed that APT increased coronary perfusion pressure and left ventricle contractility in response to coronary flow and β-agonist administration. However, treatment with PYR annulled the effects of APT. In conclusion, although chronic treatment with PYR reduces cardiac sympathetic tonic influence, it does not favor coronary bed reactivity and cardiac contractility gains. PYR treatment in the trained SHR group nullified the coronary vascular reactivity and cardiac contractility gains.

Association of sex with heart rate variability in atrial fibrillation patients

Abstract Background Sex-specific differences in cardiac autonomic tone have not been thoroughly investigated in patients with atrial fibrillation (AF) but may play a relevant role. Purpose We aimed to investigate cardiac autonomic function of female compared to male AF patients by means of short-term heart rate variability (HRV) analysis. Methods In this cross-sectional analysis, we enrolled 1150 patients from the Swiss-AF cohort study with 5-minute resting ECG recordings in sinus rhythm. We calculated the following HRV parameters: HRV triangular index (HRVI), standard deviation of NN intervals (SDNN), root mean square of successive differences, mean heart rate, power in the high frequency and low frequency range. We fitted linear regression models to analyze the association between gender and HRV variables adjusted for age, intake of betablockers, hypertension, diabetes and heart failure. Results 361 patients (29%) were female (mean age 72.9±7.8 years), 789 (68.6%) were male (mean age 69.8±8.5 years). In the multivariable adjusted models, female sex was associated with significantly lower values of HRVI (β = -0.74; 95% CI -1.44- -0 04, p=0.039) and SDNN (β = 8.95; 95% CI 0.162-17.7, p=0.046). This association persisted in all three age tertiles (<68 years, 68-75 years and ≥ 75 years of age). Conclusions In an elderly AF cohort, female sex is associated with reduced global autonomic activity. Whether this is associated with an adverse prognosis has to be investigated.

Cardiovascular Autonomic Deficits in Different Types of Achalasia.

Background and objective Achalasia cardia is a primary esophageal motility disorder, and the etiopathology of this disease's progression is not known. Moreover, autonomic dysfunction has not been studied in different types of achalasia. In light of this, we aimed to address this lack of data in this study. Methods The diagnosis of achalasia was done using high-resolution esophageal manometry (HRM)-based Chicago classification v4.0. Autonomic function tests (AFT) such as the head-up tilt test, deep breathing test (DBT), Valsalva maneuver (VM), handgrip test (HGT), and cold pressor test (CPT),as well as the heart rate variability (HRV) test, were performed among the cohort and the results were compared with those of 39 age- and sex-matched healthy controls. Results AFT and HRV tests were done on 62 patients (30 achalasia type I, 28 type II, and 4 type III) and compared with 39 age- and sex-matched healthy controls. The mean duration of symptoms, high Eckardt score, and dysphagia were most common in type I achalasia, followed by type II and III. The results of AFT showed a generalized loss of parasympathetic and baroreflex-independent sympathetic reactivity in all types of achalasia. However, baroreflex-dependent cardiovascular adrenergic reactivity was normal. Regarding cardiac autonomic tone, there was a loss of parasympathetic and sympathetic influence, but sympathovagal balance was maintained. The severity of the loss of autonomic functions was higher in type I, followed by type II. Conclusions In all types of achalasia, parasympathetic reactivity, baroreflex-independent sympathetic reactivity, and cardiac autonomic tone were lower compared to healthy controls, and the severity of dysfunction increased during the progression of the disease from type II to type I.

Abstract P299: Alteration of Cardiac Autonomic Function Through Inhalation of Biogenic Volatile Organic Compounds

Background: There is an inverse relationship between exposure to greenspaces and prevalence of cardiovascular disease and cardiovascular disease risk factors. More specifically, green exposure is associated with electrocardiogram (ECG) changes, suggesting a potential alteration of cardiac autonomic balance. One proposed mechanism by which cardiac autonomic balance may be altered is a direct physiologic effect of inhalable plant derived compounds, or biogenic volatile organic compounds (bVOCs), including limonene, α- and β-pinene which are commonly released from vegetation. Therefore, we examined the relationship between acute exposure of isolated bVOCs and cardiac autonomic tone. Hypothesis: We hypothesize that controlled exposure to isolated individual bVOCs will decrease cardiac sympathetic tone. Methods: Under controlled conditions after a bVOC washout period, healthy adults ages 18-70 were exposed to limonene (n=32), α-pinene (n=24), β-pinene (n=17), and a control (room air, n=9). Exposure consisted of one inhalation every 30 seconds for a total of 5 minutes (10 inhalations total). Pre- and post-exposure measurements of supine heart rate variability (HRV) were conducted following a 10-minute rest period. HRV was analyzed using a clean, 5-minute epoch with >95% effective data length. Statistical analysis was performed using paired t-tests to determine changes in HR and HRV. Significance level was set at p<0.05, a priori . Results: Our population was primarily female (56%, 18 of 32), white (53%, 17 of 32), high income (47%, 15 of 32), and had an education higher than a 4-year degree (62.5%, 20 of 32). There were significant decreases in HR when exposed to limonene (pre: 64.87±9.86bpm vs. post: 63.26±9.10bpm, p<.001) and α-pinene (pre: 63.98±9.32bpm vs. post: 61.64±9.72bpm, p=.008), along with trends seen in β-pinene (pre: 65.78±10.60bpm vs. post: 63.74±9.65bpm, p=.066). Control exposure showed no difference (pre: 65.40±8.38bpm vs. post: 64.14±9.35bpm, p=.301). Normalized low- (LF) and high-frequency (HF) HRV parameters showed no change across isolated bVOCs, however the LF/HF ratio scores decreased significantly following β-pinene exposure (pre: 1.62±1.69 vs. post: 0.96±0.96, p=.039). HRV time-domain parameters RMSSD and SDNN did not change following isolate exposure. Conclusions: Post-exposure decreases in HR and LFHF ratios indicate the potential for cardiovascular disease risk reduction from bVOC exposure leading to decreased sympathetic tone. Additional work is required to determine the mechanism of exposure-related changes.

Long Sudarshan Kriya Yoga enhances cardiovascular and respiratory synchronization: An observational study

BackgroundSudarshan Kriya Yoga (SKY – a rhythmic cyclic breathing) is known to produce several physiological changes in human body. Earlier it has been reported that SKY improves cardiovascular modulations, namely increase in heart rate variability. ObjectiveTo observe the synchronization in oscillatory modulations in cardiac autonomic tone and ventilatory exchange during Long Sudarshan Kriya Yoga (LSKY). LSKY is a sequential combination of pranayama in ujjayi breath, bhastrika, and cyclic rhythmic breathing followed by yog-nidra. MethodsRegular LSKY practitioners from the Art of Living community with more than two years of experience participated in the study (n = 22; age 40.09 ± 12.68). The Electrocardiogram (ECG), respiration, oxygen saturation, and concentrations of oxygen and carbon-di-oxide from exhaled air were recorded before and during LSKY. The time domain parameters of heart rate variability (HRV) were calculated from ECG. All parameters were compared and correlated at each stage of LSKY. ResultsHighly significant reciprocal correlation was found between HRV parameters and respiration rate during LSKY. Both O2 consumption and CO2 production increased significantly during three stages of pranayama and decreased towards the end of cyclic breathing. We also saw increased SPO2 simultaneously. ConclusionThe autonomic parameters exhibited reciprocal response to respiratory rate and correlated well to the ventilatory parameters. Further during LSKY we observed enhanced synchronization. In conclusion the LSKY has a potential to influence cardiorespiratory parameters for improving the performance of both systems. LSKY - enhances oscillations in HRV that resets the autonomic system, indicative of better cardiac health and prepares body for better metabolic response. Such changes are capable of inducing resilience along with physiological, psychological relaxation and emotional well-being.

Assessment of the relationship of systemic vascular dysfunction and cardiac autonomic neuropathy (CAN) with diabetic retinopathy.

Diabetic retinopathy, a form of microvasculopathy, is the leading cause of the visual abnormality. However, there is no conclusive evidence of the relationship of systemic vascular dysfunction with retinal microvasculopathy. In addition, diabetes-associated cardiac autonomic neuropathy may also compromise vascular function. The present study intends to correlate arterial stiffness, endothelial function, and heart rate variability (HRV) as a standardized measure of cardiac autonomic neuropathy with diabetic retinopathy. The present cross-sectional, observational study was conducted in the Department of Physiology. Twenty subjects were recruited in group 1 (T2DM, type 2 diabetes mellitus patients, without retinopathy) and group 2 (T2DM with retinopathy). The vascular parameters such as heart rate, peripheral and central blood pressure, augmentation index [AIx (%)], brachial -ankle pulse wave velocity (baPWV), and reactive hyperaemia index (RHI) were recorded. Independent sample t-test (for parametric data) and Mann-Whitney U test (for non-parametric data) were employed to compare the variables of two groups. Spearman correlation was used to examine the relationship among the parameters. Linear regression analysis was performed to examine the important vascular predictor for diabetic retinopathy. baPWV was significantly higher in group 2 than in group 1 and positively associated with group 2. RHI was significantly less in group 2 than group 1 and negatively associated with group 2. Among HRV metrics, standard deviation of successive differences (SDSD), root mean square of successive differences between normal heartbeats (RMSSD), and high frequency (HF) power were significantly decreased in group 2 than in group 1. SDSD, RMSSD, and HF power were negatively associated with group 2. RHI emerged as a significant predictor of diabetic retinopathy following linear regression. Overall, the result of the present study indicates that metabolic dysregulation of glucose may affect the normal functioning of the autonomic nervous system and vascular function. Therefore, screening of vascular function and cardiac autonomic tone may be advocated in diabetic patients in routine clinics to examine the existence of any comorbid condition, such as diabetic retinopathy, as systemic vascular changes may also affect ophthalmic vasculature.

Acute poisoning by chlorpyrifos differentially impacts survival and cardiorespiratory function in normotensive and hypertensive rats

Hypertension is the most important and well-known risk factor for cardiovascular disease (CVD). Recently, acute organophosphate (OP) poisoning has also been pointed as a CVD risk factor. Despite this evidence, no studies have contrasted the acute toxicosis and cardiovascular (CV) effects of OP poisoning under conditions of normotension and hypertension. In this work, adult male normotensive Wistar and Spontaneously Hypertensive rats (SHR) were intraperitoneally injected with saline or chlorpyrifos (CPF), an OP compound, monitored for acute toxicosis signs and 24-h survival. After poisoning, blood pressure, heart rate and ventilation were recorded, the Bezold-Jarisch Reflex (BJR), the Chemoreflex (CR) were chemically activated, as well as the cardiac autonomic tone (AUT) was assessed. Erythrocyte and brainstem acetylcholinesterase and plasmatic butyrylcholinesterase (BuChE) activities were measured as well as lipid peroxidation, advanced oxidation protein products (AOPP), nitrite/nitrate levels, expression of catalase, TNFα and angiotensin-I converting enzyme (ACE-1) within the brainstem. CPF induced a much more pronounced acute toxicosis and 33 % lethality in SHR. CPF poisoning impaired ventilation in SHR, the BJR reflex responses in Wistar rats, and the chemoreflex tachypneic response in both strains. CPF inhibited activity of cholinesterases in both strains, increased AOPP and nitrite/nitrate levels and expression of TNFα and ACE-1 in the brainstem of Wistar rats. Interestingly, SHR presented a reduced intrinsic BuChE activity, an important bioscavenger. Our findings show that, CPF at sublethal doses in normotensive rats lead to lethality and much more pronounced acute toxicity signs in the SHR. We also showed that cardiorespiratory reflexes were differentially impacted after CPF poisoning in both strains and that the cardiorespiratory disfunction seems to be associated with interference in cholinergic transmission, oxidative stress and inflammation. These results points to an increased susceptibility to acute toxicosis in hypertension, which may impose a significant risk to vulnerable populations.

Comparative Study of Heart Rate Variability in Patients with Major Depressive Disorder and Normal Subjects

Introduction: Major Depressive Disorder is a mood disorder diagnosed on the basis of DSM-5 criteria. Cardiovascular disorders are among the most common causes of deaths worldwide, accounting for about one-third of the mortality in both genders. Cardiac illnesses seem to have a bidirectional relationship with depression. Altered cardiac autonomic tone remains one of the most plausible explanations, which also appears to be a central biological substrate linking depression to a number of concurrent physical (e.g., cardiovascular) dysfunctions. Heart Rate Variability has become the conventionally accepted term to describe variations of both instantaneous heart rate and RR intervals (measured in ms) obtained from ECG or plethysmogram. Material and Method: This study was a prospective observational study involved 150 individuals divided into two groups. Group A – Patients having first episode major depression or new recurrent depressive episode recruited from psychiatric OPD (n=75), Group B– Age, Sex, Height and Weight matched healthy controls (n=75). Results: In our study, among the time domain indices, Mean heart rate was increased in MDD patients in comparison to healthy controls and the difference was statistically significant. Root mean square of successive differences was reduced in MDD patients in comparison to healthy controls and the difference was statistically significant. Standard deviation of NN intervals and percentage of NN intervals differing by >50 ms also showed reduction in depressed patients than controls, but the difference was not statistically significant. The frequency domain indices Total power, very low frequency, High frequency were reduced in MDD patients in comparison to healthy controls and the difference was statistically significant. Low Frequency and Low Frequency / High Frequency ratio were increased in patients of MDD in comparison to healthy controls and the difference was statistically significant. Conclusion: From our study we can conclude that HRV is reduced in MDD patients. We suggest that HRV parameters can be used as diagnostic or predictive biomarkers of depression. Keywords: Major Depressive Disorder (MDD), cardiovascular disease (CVD), Heart Rate Variability (HRV), Time Domain Indices, Frequency Domain Indices.

Wildfire-related smoke inhalation worsens cardiovascular risk in sleep disrupted rats.

As a lifestyle factor, poor sleep status is associated with increased cardiovascular morbidity and mortality and may be influenced by environmental stressors, including air pollution. To determine whether exposure to air pollution modified cardiovascular effects of sleep disruption, we evaluated the effects of single or repeated (twice/wk for 4 wks) inhalation exposure to eucalyptus wood smoke (ES; 964 μg/m3 for 1 h), a key wildland fire air pollution source, on mild sleep loss in the form of gentle handling in rats. Blood pressure (BP) radiotelemetry and echocardiography were evaluated along with assessments of lung and systemic inflammation, cardiac and hypothalamic gene expression, and heart rate variability (HRV), a measure of cardiac autonomic tone. GH alone disrupted sleep, as evidenced by active period-like locomotor activity, and increases in BP, heart rate (HR), and hypothalamic expression of the circadian gene Per2. A single bout of sleep disruption and ES, but neither alone, increased HR and BP as rats transitioned into their active period, a period aligned with a critical early morning window for stroke risk in humans. These responses were immediately preceded by reduced HRV, indicating increased cardiac sympathetic tone. In addition, only sleep disrupted rats exposed to ES had increased HR and BP during the final sleep disruption period. These rats also had increased cardiac output and cardiac expression of genes related to adrenergic function, and regulation of vasoconstriction and systemic blood pressure one day after final ES exposure. There was little evidence of lung or systemic inflammation, except for increases in serum LDL cholesterol and alanine aminotransferase. These results suggest that inhaled air pollution increases sleep perturbation-related cardiovascular risk, potentially in part by increased sympathetic activity.

Acute exposure to chlorpyrifos differentially impacts survival and cardiovascular function of normotensive and hypertensive rats

Hypertension is the most important and well-known risk factor for cardiovascular disease (CVD). Recently, acute organophosphate (OP) poisoning has also been pointed as a CVD risk factor. Despite these evidence, no studies have contrasted the cardiovascular (CV) effects of OP poisoning under conditions of normotension and hypertension. We hypothesized that hypertensive rats would have a greater impairment of CV function after acute exposure to chlorpyrifos (CPF), an OP compound. 12-14 week-old male normotensive Wistar and Spontaneously Hypertensive rats (SHRs) were intraperitoneally (i.p.) injected with saline (NaCl 0.9%) or 20 mg.kg-1 of CPF, a previously shown sublethal dose in normotensive rats. 24-hour survival was recorded and through cannulation of the femoral artery and vein, we assessed blood pressure (BP) and heart rate (HR) recordings and chemically activated the Bezold-Jarisch Reflex (BJR), the Chemoreflex (CR), as well as assessed the cardiac autonomic tone (AUT). BJR was activated by phenylbiguanide (PBG; 1.5; 3; 6; 12; 24 μg/kg; i.v.) and the CR by potassium cyanide (KCN, 10, 20, 40 and 80 μg/ rat; i.v.) injections, while the AUT was assessed by pharmacological blockade with atenolol (4mg.kg-1, i.v) and atropine (2mg.kg-1, i.v). CPF acute exposure induced 33% mortality in SHR without leading to lethality in Wistar rats. CPF poisoning impaired the BJR hypotensive response in Wistar rats for all PBG doses tested (ΔDBP: - 33.83±4.88 vs. -14.16±2.68; -44.58±3.48 vs. -30.58±2.16; -66.16±2.50 vs. -36.16±2.54; -72.66±2.66 vs. -47.91±2.50; -78.66±2.35 vs.-61.58±2.40; p<0.05 Wistar saline vs Wistar CPF) and the bradycardic response at the dose of 6 and 12μg/kg, respectively (ΔHR: -268.66±14.77 vs. -216.66±11.11; -304.58±13.42 vs. -241.66±11.01; p<0.05 Wistar saline vs Wistar CPF), without affecting the SHR strain. No CPF-induced changes were observed for the CR and AUT between strains. Our findings show that, despite being sublethal in normotensive rats, CPF lead to mortality in hypertensive rats. However, contrary to our hypothesis, CPF poisoning did not further impaired CV function in SHR, but significantly worsen BJR function in Wistar rats. Despite not producing greater impairment in CV function, CPF poisoning leads to greater mortality under hypertension, which may impose a significant risk in individuals with this comorbidity. Aitken AV, was recipeint of Fapes Foundation scholarship. Minassa VS, Batista TJ were recipients of Capes Foundation scholarship. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of sleep fragmentation and partial sleep restriction on heart rate variability during night

We developed a cross-over study design with two interventions in randomized order to compare the effects of sleep fragmentation and partial sleep restriction on cardiac autonomic tone. Twenty male subjects (40.6 ± 7.5 years old) underwent overnight polysomnography during 2 weeks, each week containing one undisturbed baseline night, one intervention night (either sleep restriction with 5 h of sleep or sleep fragmentation with awakening every hour) and two undisturbed recovery nights. Parameters of heart rate variability (HRV) were used to assess cardiac autonomic modulation during the nights. Sleep restriction showed significant higher heart rate (p = 0.018) and lower HRV-pNN50 (p = 0.012) during sleep stage N1 and lower HRV-SDNN (p = 0.009) during wakefulness compared to the respective baseline. For HR and SDNN there were recovery effects. There was no significant difference comparing fragmentation night and its baseline. Comparing both intervention nights, sleep restriction had lower HRV high frequency (HF) components in stage N1 (p = 0.018) and stage N2 (p = 0.012), lower HRV low frequency (LF) (p = 0.007) regarding the entire night and lower SDNN (p = 0.033) during WASO during sleep. Sleep restriction increases sympathetic tone and decreases vagal tone during night causing increased autonomic stress, while fragmented sleep does not affect cardiac autonomic parameters in our sample.

Heart rate variability in patients presenting with anginal symptoms in absence of cardiac and other diseases

Objectives: Angina is a symptom of coronary artery disease (CAD). Modulation of cardiac autonomic tone as assessed by heart rate (HR) variability (HRV) is found reduced in patients with CAD; myocardial ischemia, myocardial infarction and some other cardiovascular diseases. Reduced HRV has been found associated with sudden cardiac death in these CAD patients. Several patients present with anginal symptoms clinically in absence of CAD or other diseases. The status of HRV is not much clear in these patients. Thus, we aimed to assess HRV in patients with angina with and without myocardial ischemia and compare it with HRV of healthy subjects of similar age groups and follow-up patients for 1 year for cardiac/health events. Materials and Methods: The study included 61 consecutive male patients clinically presenting with angina and 30 healthy subjects. Based on Thallium-201 myocardial perfusion Single-photon emission computerized tomography (SPECT) imaging, patients were divided into two groups; patients with myocardial perfusion defects (MPD), (n = 33, age 54.91 ± 7.43 years) and patients with no MPD (NMPD), NMPD (n = 28, age 53.04 ± 8.50 years). Short-term HRV was assessed in all patients and subjects in resting supine position following standard protocol. All MPD and 25 NMPD patients could be followed up for 1 year for cardiac/health events. Results: Surprisingly, the NMPD patients showed significantly reduced HRV, Standard deviation of the N-N intervals, The square root of the mean squared differences of successive N-N intervals, Percentage of the number of interval differences of successive N-N intervals greater than >50 ms divided by total number of R-R intervals, low frequency (LF) power, High Frequency (HF) power and total power as compared to both MPD patients and healthy subjects. (Total power [NMPD vs. MPD]: 610.1 [379.9–1072.8] vs. 1508.0 [748.4–2339.4] millisecond squares (ms2), P = 0.001), healthy subjects (Total power: 1414.6 [1104.6-2141.5] ms2, P = 0.001). The markers of sympathetic tone; LF (normalised unit) and LF/HF ratio were higher in NMPD patients as compared to MPD patients resulting in an altered sympathovagal balance. During a 1-year follow-up, sudden death was seen in one MPD patient (3.1%) and two NMPD patients (8%). Conclusion: The NMPD patients showed significantly reduced HRV as compared to both MPD patients and Healthy subjects with an altered sympathovagal balance. Sudden death was also seen in NMPD patients as MPD patients.

Medetomidine/midazolam/fentanyl narcosis alters cardiac autonomic tone leading to conduction disorders and arrhythmias in mice

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.

Could Heart Rate Variability Serve as a Prognostic Factor in Patients with Pulmonary Hypertension? A Single-center Pilot Study.

Heart rate variability (HRV), which is defined as cyclic changes in sinus rate with time, is used as a measure of cardiac autonomic tone. Our aim was to determine the impact of HRV on short-term prognosis in pulmonary hypertension (PH). We enrolled 64 PH patients and 69 healthy subjects (control group). Patients were evaluated by Holter-ECG, echocardiography, and laboratory tests. 24-h Holter-ECG monitoring was used for HRV. The development of adverse events (right heart failure, hospitalization, syncope, and death) during the 6-month follow-up was evaluated in PH group. PH group (39 ± 16 years, 37.5% males) comprised of 16 patients with idiopathic pulmonary arterial hypertension (PAH) (25%), 36 patients with PAH associated with congenital heart disease (56.3%), 3 PAH associated with connective tissue disease (4.7%), 1 with portopulmonary (1.6%), and 8 chronic thromboembolic PH (12.5%). The time-dependent (standard deviation of all NN intervals for a selected time period [SDNN], standard deviation of the 5-min mean R-R intervals tabulated over an entire day [SDANN], SDNN Index, and Triangular Index) and frequency-dependent HRV indices (low frequency, high-frequency power, and total power,) were significantly reduced in those with PH. Functional class was negatively associated with SDNN, SDANN, SDNN Index, and Triangular Index. Adverse events developed in 25% of the patients during the 6-month follow-up period (200 ± 92 days) (7 patients had right-heart failure, 5 syncope, 12 patients were hospitalized, and 9 had died). All the time and frequency-dependent indices significantly associated with adverse events. Mortality correlated with SDNN (rS = -0.354, P = 0.005), SDANN (rS = -0.368, P = 0.004), SDNN Index (rS = -0.257, P = 0.045), Triangular Index (rS = -0.310, P = 0.014), and VLF (rS = -0.265, P = 0.039). HRV is significantly depressed in patients with PH and is associated with the clinical status. HRV indices might predict clinical deterioration, adverse events, and mortality for 6 months. Non-invasive assessment of HRV through Holter-ECG may be a valuable and practical tool in risk stratification of patients with PH for short-term outcomes.

Intermittent exposure to chlorpyrifos results in cardiac hypertrophy and oxidative stress in rats

Forbidden in some countries due to its proven toxicity to humans, chlorpyrifos (CPF) still stands as an organophosphate pesticide (OP) highly used worldwide. Cardiotoxicity assessment is an unmet need in pesticide regulation and should be deeply studied through different approaches to better inform and generate an appropriate regulatory response to OP use. In the present study, we used our 4-week intermittent OP exposure model in rats to address the CPF effects on cardiac morphology allied with cardiovascular functional and biomolecular evaluation. Rats were intermittently treated with CPF at doses of 7 mg/kg and 10 mg/kg or saline (i.p.) and assessed for cardiac morphology (cardiomyocyte diameter and collagen content), cardiopulmonary Bezold-Jarisch reflex (BJR) function, cardiac autonomic tone, left ventricle (LV) contractility, cardiac expression of NADPH oxidase (Nox2), catalase (CAT), superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2) and cardiac levels of advanced oxidation protein products (AOPP) and thiobarbituric acid reactive substances (TBARS). Plasma butyrylcholinesterase (BuChE) and brainstem acetylcholinesterase (AChE) were also measured. Intermittent exposure to CPF induced cardiac hypertrophy, increasing cardiomyocyte diameter and collagen content. An impairment of cardioinhibitory BJR responses and an increase in cardiac vagal tone were also observed in CPF-treated animals without changes in LV contractility. CPF exposure increased cardiac Nox-2, CAT, SOD1, and TBARS levels and inhibited plasma BuChE and brainstem AChE activities. Our data showed that intermittent exposure to CPF induces cardiac hypertrophy together with cardiovascular reflex impairment, imbalance of autonomic tone and oxidative stress, which may bring significant cardiovascular risk to individuals exposed to OP compounds seasonally.

Perinatal Exposure to Bisphenol A and Developmental Programming of the Cardiovascular Changes in the Offspring.

Bisphenol A (BPA) is an industrial ubiquitous compound, frequently used to produce synthetic polymers and epoxy resins. BPA is a well-recognized endocrine disruptor and xenoestrogen compound. Evidence from epidemiological and experimental studies suggests that perinatal BPA exposure (gestation and/or lactation) increases the risk of developing various diseases, including the cardiovascular system. Developmental programming refers to environmental insults during the critical window of development that affect the structure and physiology of body systems, causing permanent changes in later stages. BPA influences the developmental programming of non-communicable diseases in the offspring. In the present review, we discuss the developmental programming of cardiovascular diseases related to perinatal exposure to BPA, supported by epidemiological and experimental evidence from published literature. The majority of the reported studies found a positive association between perinatal BPA exposure and adverse cardiovascular repercussions in the fetal, neonatal, and adulthood stages. The possible underlying mechanisms include epigenetic modifications of genes involved in cardiac muscle development, autonomic tone, collagenous and non-collagenous extracellular matrix, cardiac remodeling and calcium homeostasis, and mitochondrial energy metabolism. Epigenetics can modify the outcome of any disease. Hence, in the present review, we also discuss the role of epigenetics in preventing cardiovascular diseases following perinatal exposure to BPA. We also highlight how future treatment and drug delivery related to cardiovascular involvement could be based on epigenetic markers.

Open-chest Pulsed Electric Field Ablation of Cardiac Ganglionated Plexi in Acute Canine Models.

This study aimed to evaluate the safety and acute effect on markers of cardiac autonomic tone following pulsed electric fields (PEFs) delivered to epicardial ganglionated plexi (GP) during a cardiac surgical procedure. Ablation of GP as a treatment for atrial fibrillation (AF) has shown promise, but thermal ablation energy sources are limited by the risk of inadvertent collateral tissue injury. In acute canine experiments, median sternotomy was performed to facilitate the identification of 5 epicardial GP regions using an anatomy-guided approach. Each site was targeted with saline-irrigated PEF (1000 V, 100 μs, 10 electrocardiogram [ECG]-synchronized pulse sequences). Atrial effective refractory period (AERP) and local electrogram (EGM) amplitude were measured before and after each treatment. Histology was performed on samples from treatment-adjacent structures. In 5 animals, 30 (n = 2) and 60 (n = 3) pulses were successfully delivered to each of the 5 target sites. There was no difference in local atrial EGM amplitude before and after PEF application at each site (1.83 ± 0.41 vs. 1.92 ± 0.53 mV, P = .72). The mean AERP increased from 97 ± 15 ms at baseline to 115 ± 7 ms following treatment at all sites (18.6% increase; 95% confidence interval, 1.9–35.2; P = .037). There were no sustained ventricular arrhythmias or acute evidence of ischemia following delivery. Histology showed complete preservation of adjacent atrial myocardium, phrenic nerves, pericardium, and esophagus. Use of PEF to target regions rich in cardiac GP in open-chest canine experiments was feasible and effective at acutely altering markers of cardiac autonomic tone.

Resting heart rate predicts cardiac autonomic modulation during passive head-up tilt in subjects without cardiovascular diseases

Background Resting heart rate (HR) and its variability (HRV) reflects the cardiac sympathovagal balance that is stimulated by head-up tilting. HRV is influenced by the level of HR, but how much HRV offers additional information about cardiac autonomic tone than HR alone remains unresolved. We examined the relation of resting HR with HRV during head-up tilt. Methods. Hemodynamics of 569 subjects without known cardiovascular diseases and medications with direct cardiovascular effects were recorded using whole-body impedance cardiography, radial pulse wave analysis, and electrocardiography-based HRV analysis during passive head-up tilt. Results. Higher low frequency to the high-frequency ratio (LF/HF) of HRV (reflecting sympathovagal balance) was associated with higher HR in supine (p < .05, both linear regression analysis and variance analysis comparing HR tertiles) and upright postures (p < .001, linear regression analysis). The association of HR with HRV during tilt-testing remained significant when the HR dependence of HRV was mathematically weakened by dividing the HRV power spectra with the fourth power of the average RR-interval. Conclusion. Higher resting HR is related to higher LF/HF both supine and upright, reflecting elevated sympathetic influence on cardiac autonomic modulation. Lower resting HR is associated with lower resting LF/HF, while the differences in LF/HF between the HR tertiles were minor during head-up tilt, suggesting a greater change in cardiac sympathovagal balance in response to upright posture in those with lowest resting HR. Altogether, resting HR well predicts HRV levels during head-up tilt. Trial registration: Clinicaltrialsregister.eu 2006-002065-39, first registered 5 May 2006. ClinicalTrials.gov NCT01742702, first registered 5 December 2012.

Heart rate variability as a function of menopausal status, menstrual cycle phase, and estradiol level.

Low estradiol status is associated with increased cardiovascular risk. We sought to determine the association between heart rate variability (HRV), a marker of cardiovascular risk, at baseline and in response to stressor as a function of menopausal status, menstrual cycle phase and estradiol level. Forty‐one healthy women (13 postmenopausal, 28 premenopausal) were studied. Eleven premenopausal women were additionally studied in the high and low estradiol phases of the menstrual cycle. HRV was calculated by spectral power analysis (low Frequency (LF), high frequency (HF) and LF:HF) at baseline and in response to graded Angiotensin II (AngII) infusion. The primary outcomes were differences in HRV at baseline and in response to AngII. Compared to premenopausal women in the low estradiol phase, postmenopausal women demonstrated lower baseline LF (p = 0.01) and HF (p < 0.001) measures, which were not significant after adjustment for age and BMI. In response to AngII, a decrease in cardioprotective HRV (ΔHF = −0.43 ± 0.46 ln ms2, p = 0.005 vs. baseline) was observed in postmenopausal women versus premenopausal women. Baseline HRV parameters did not differ by menstrual phase in premenopausal women. During the low estradiol phase, no differences were observed in the HRV response to AngII challenge. In contrast, women in the high estradiol phase were unable to maintain HRV (ΔLF = −0.07 ± 0.46 ln ms2, p = 0.048 response vs. baseline, ΔHF = −0.33 ± 0.74 ln ms2, p = 0.048 response vs. baseline). No association was observed between any measure of HRV and estradiol level. Menopausal status and the high estradiol phase in premenopausal women were associated with reduced HRV, a marker of cardiovascular risk. Understanding the role of estradiol in the modulation of cardiac autonomic tone may help guide risk reduction strategies in women.