Neuromodulation of Cardiac Ischemic Pain: Role of the Autonomic Nervous System and Vasopressin.

Cardiac pain is an index of cardiac ischemia that helps the detection of cardiac hypoxia and adjustment of activity in the sufferer. Drivers and thresholds of cardiac pain markedly differ in different subjects and can oscillate in the same individual, showing a distinct circadian rhythmicity and clinical picture. In patients with syndrome X or silent ischemia, cardiac pain intensity may cause neurogenic stress that potentiates the cardiac work and intensifies the cardiac hypoxia and discomfort of the patient. The reasons for individual differences in cardiac pain sensation are not fully understood. Thus far, most attention has been focused on inappropriate regulation of the heart by the autonomic nervous system, autacoids, and cardiovascular hormones. Herein, we summarize evidence showing that the autonomic nervous system regulates cardiac pain sensation in cooperation with vasopressin (AVP). AVP is an essential analgesic compound and it exerts its antinociceptive function through actions in the brain (the periaqueductal gray, caudate nucleus, nucleus raphe magnus), spinal cord, and heart and coronary vessels. Vasopressin acts directly by means of V1 and V2 receptors as well as through multiple interactions with the autonomic nervous system and cardiovascular hormones, in particular, angiotensin II and endothelin. The pain regulatory effects of the autonomic nervous system and vasopressin are significantly impaired in cardiovascular diseases.

Household food insecurity is associated with greater autonomic dysfunction testing score in Latinos with type 2 diabetes.

AIM: We examined household food insecurity (HFI) and autonomic nervous system (ANS) function in a subset of low-income Latinos with type 2 diabetes with data from a stress management trial. METHODS: InclusionLatino or Hispanic, Spanish speaking, age less than 18 years, ambulatory status, type 2 diabetes more than 6 months, A1c less than 7.0%. ExclusionPain or dysfunction in hands (e.g., arthritis) precluding handgrip testing; medical or psychiatric instability. HFI was assessed with the 6-item U.S. household food security survey module; with responses to > = 1 question considered HFI. An ANS dysfunction index was calculated from xix autonomic function tests which were scored 0 = normal or 1 = abnormal based on normative cutoffs and then summed. Autonomic function tests were: 1) 24-hour heart rate variability as reflected in standard deviation of the normal-to-normal (SDNN) heart rate acquired with 3-channel, 7-lead ambulatory electrocardiogram (Holter) monitors; 2) difference between the highest diastolic blood pressure (DBP) during sustained handgrip and the average DBP at rest; 3) difference between baseline supine and the minimal BP after standing up; and, from 24-hour urine specimens 4) cortisol, 5) normetanephrine, and, 6) metanephrine. RESULTS: Thirty-five individuals participated, 23 (65.7%) of them were women, age mean = 61.6 (standard deviation = 11.2) years, HbA1c mean = 8.5% (standard deviation = 1.6) and 20 participants (57.1%) used insulin. Twenty-two participants (62.9%) reported HFI and 25 (71.4%) had one or more abnormal ANS measure. Independent t-tests showed that participants with HFI had a higher ANS dysfunction index (mean = 1.5, standard deviation = 0.9) than patients who were food secure (mean = 0.7, standard deviation = 0.8), p = 0.02. Controlling for financial strain did not change significance. Total ANS index was not related to glycemia, insulin use or other socioeconomic indicators. In this sample, HFI was associated with ANS dysfunction. Policies to improve food access and affordability may benefit health outcomes for Latinos with diabetes.

Cardiovascular autonomic modulation during passive heating protocols: a systematic review.

Objective.To conduct a systematic review of the possible effects of passive heating protocols on cardiovascular autonomic control in healthy individuals.Approach.The studies were obtained from MEDLINE (PubMed), LILACS (BVS), EUROPE PMC (PMC), and SCOPUS databases, simultaneously. Studies were considered eligible if they employed passive heating protocols and investigated cardiovascular autonomic control by spontaneous methods, such as heart rate variability (HRV), systolic blood pressure variability (SBPV), and baroreflex sensitivity (BRS), in healthy adults. The revised Cochrane risk-of-bias tool (RoB-2) was used to assess the risk of bias in each study.Main results.Twenty-seven studies were included in the qualitative synthesis. Whole-body heating protocols caused a reduction in cardiac vagal modulation in 14 studies, and two studies reported both increased sympathetic modulation and vagal withdrawal. Contrariwise, local-heating protocols and sauna bathing seem to increase cardiac vagal modulation. A reduction of BRS was reported in most of the studies that used whole-body heating protocols. However, heating effects on BRS remain controversial due to methodological differences among baroreflex analysis and heating protocols.Significance.Whole-body heat stress may increase sympathetic and reduce vagal modulation to the heart in healthy adults. On the other hand, local-heating therapy and sauna bathing seem to increase cardiac vagal modulation, opposing sympathetic modulation. Nonetheless, further studies should investigate acute and chronic effects of thermal therapy on cardiovascular autonomic control.

Acute high-intensity interval exercise versus moderate-intensity continuous exercise in heated water-based on hemodynamic, cardiac autonomic, and vascular responses in older individuals with hypertension.

OBJECTIVES: This crossover study design aimed to assess hemodynamic, cardiac autonomic, and vascular responses to high-intensity interval (HIIE) vs moderate-intensity continuous exercise (MICE) in older individuals with hypertension. METHODS: Twenty (67 ± 7 y) older individuals with hypertension were randomly assigned to perform HIIE, MICE, or control (CON) sessions in the heated swimming pool (30-32°C). Blood pressure (BP), arterial stiffness, endothelial reactivity, and heart rate variability (HRV) were measured pre, post, and 45 min (recovery) after each intervention followed by 24-h ambulatory BP and HRV. RESULTS: One single aerobic exercise session was not effective to provoke post-exercise hypotension and vascular improvements. HIIE was superior to MICE and CON to increasing parasympathetic modulation at post and recovery. Exercise sessions showed to disturb the autonomic system at nighttime compared to CON. CONCLUSIONS: These results may have important implications in water-based therapy and the elderly with hypertension.

Postoperative Curative Effect of Cardiac Surgery Diagnosed by Compressed Sensing Algorithm-Based E-Health CT Image Information and Effect of Baduanjin Exercise on Cardiac Autonomic Nerve Function of Patients.

This research was aimed at exploring the effect of CT images reconstructed by optimized compressed sensing algorithm on postoperative diagnosis of patients with hypertensive heart disease and the influence of Baduanjin on cardiac autonomic nerve function. Based on the compressed sensing algorithm, the maximum likelihood expectation maximization algorithm was introduced to optimize it, and the optimization algorithm was established. The optimized algorithm and filtered back projection algorithm (FBP) were compared regarding the root mean squared error (RMSE), peak signal-to-noise ratio (PSNR), and structural similar image metric (SSIM). A total of 126 patients with hypertensive heart disease who underwent CT examination in the hospital were selected as study subjects. According to whether Baduanjin intervention was adopted, patients were divided into observation group (conventional treatment +Baduanjin) and control group (conventional treatment), with 63 patients in each group. The effect of CT examination on postoperative diagnosis was analyzed. Systolic blood pressure (SBP), diastolic blood pressure (DBP), differential pressure (DP), respiratory rate and heart rate (HR), very low-frequency (VLF) power, low-frequency (LF) power, high-frequency (HF) power, total power (TP) of HR variability, and changes in LF/HF of patients before and after treatment were compared. The RMSE of the compressed sensing optimization algorithm (3.28 ± 0.36) was significantly lower than that of the FBP algorithm (9.25 ± 1.03) (P < 0.05). The SSIM and PNSR of the compressed sensing optimization algorithm were (0.87 ± 0.10) and (21.22 ± 1.60) dB, respectively. The SSIM was significantly higher than the FBP algorithm (P < 0.01), and the PNSR was also higher than the FBP algorithm (P < 0.05). The detection rate of CT for pleural effusion was 16 cases (25.40%) higher than 5 cases (7.94%) with TTE (P < 0.01). After treatment, SBP, DBP, HR, LF, VLF, LF/HF, and DP values in the observation group were lower than those in the control group (P < 0.05), and TP and HF were higher than those in the control group (P < 0.05). It suggested that a novel algorithm was established based on compressed sensing algorithm to improve image quality. CT image had important guiding significance for postoperative diagnosis of heart. Baduanjin intervention could improve the integrated function of patient's autonomic nervous system and the regulation ability of the vagus nerve.

Autonomic Neuromodulation for Atrial Fibrillation Following Cardiac Surgery: JACC Review Topic of the Week.

Autonomic neuromodulation therapies (ANMTs) (ie, ganglionated plexus ablation, epicardial injections for temporary neurotoxicity, low-level vagus nerve stimulation [LL-VNS], stellate ganglion block, baroreceptor stimulation, spinal cord stimulation, and renal nerve denervation) constitute an emerging therapeutic approach for arrhythmias. Very little is known about ANMTs' preventive potential for postoperative atrial fibrillation (POAF) after cardiac surgery. The purpose of this review is to summarize and critically appraise the currently available evidence. Herein, the authors conducted a systematic review of 922 articles that yielded 7 randomized controlled trials. In the meta-analysis, ANMTs reduced POAF incidence (OR: 0.37; 95% CI: 0.25 to 0.55) and burden (mean difference [MD]: -3.51 hours; 95% CI: -6.64 to -0.38 hours), length of stay (MD: -0.82 days; 95% CI: -1.59 to -0.04 days), and interleukin-6 (MD: -79.92 pg/mL; 95% CI: -151.12 to -8.33 pg/mL), mainly attributed to LL-VNS and epicardial injections. Moving forward, these findings establish a base for future larger and comparative trials with ANMTs, to optimize and expand their use.

Antioxidant therapy reverses sympathetic dysfunction, oxidative stress, and hypertension in male hyperadipose rats.

AIMS: The rostral ventrolateral medulla (RVLM) is the main sympathetic output of the central nervous system to control blood pressure. Reportedly, reactive oxygen species (ROS) can increase arterial pressure, leading to hypertension. As ROS increase the sympathetic tone in RVLM and obese animals present grater oxidative stress, it would be important to note this relationship. MAIN METHODS: Therefore, we evaluated the systemic and central effects (in the RVLM) of vitamin C (vit C, an antioxidant) on the redox balance and cardiovascular and autonomic profiles in hyperadipose male rats. We also evaluated the neurotransmission by L-glutamate (L-glu) and vit C in the RVLM of awake hyperadipose rats. KEY FINDINGS: Our study confirmed that hyperadipose rats were hypertensive and tachycardic, presented increased sympathetic and decreased parasympathetic modulation of the heart, and had increased plasma lipoperoxidation compared with the control rats (CTR). Oral vitamin C treatment reverted cardiovascular, autonomic, and plasma redox dysfunction. Hyperadipose rats presented a higher blood pressure increase after L-glu microinjection and a lower response to vit C in the RVLM compared with the CTR group. Biochemical analysis of redox balance in RVLM punches showed that hyperadipose rats have increased NBT and T-BARS, and after treatment with vit C, the oxidative profile decreased. The antioxidative activity of vit C reduced the amount of ROS in the RVLM area that might have resulted in lowered blood pressure and sympathetic modulation. SIGNIFICANCE: Our data suggest central and peripheral benefits of vit C treatment on cardiovascular, autonomic, and oxidative dysfunctions in hyperadipose animals.

Cardiac Autonomic Modulation in Subjects with Amyotrophic Lateral Sclerosis (ALS) during an Upper Limb Virtual Reality Task: A Prospective Control Trial.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. As a result of the rapid progression and severity of the disease, people with ALS experience loss of functionality and independence. Furthermore, it has already been described presence of autonomic dysfunction. Despite the increasing use of virtual reality (VR) in the treatment of different diseases, the use of virtual reality environment as an intervention program for ALS patients is innovative. The benefits and limitations have not yet been proven. Our objective was to evaluate the autonomic function of individuals with amyotrophic lateral sclerosis throughout the virtual reality task. The analysis of autonomic function was completed before, during, and after the virtual reality task using the upper limbs; also, all steps lasted ten minutes in a sitting position. Heart rate variability (HRV) was taken via the Polar® RS800CX cardiofrequencymeter. The following questionnaire was enforced: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS) and Fatigue Severity Scale (FSS). Different types of HRV were revealed for the groups, indicating that the ALS group has reduced HRV, with most of the representative indices of the sympathetic nervous system. Besides, the physiological process of reducing parasympathetic activity from rest to VR activity (vagal withdrawal), with reduction in HF (ms2) and an increase in HR from rest to activity, and a further increase throughout recovery, with withdrawal of sympathetic nervous system, occurs just for the control group (CG), with no alterations between rest, activity, and recovery in individuals with ALS. We could conclude that patients with ALS have the reduction of HRV with the sympathetic predominance when equated to the healthy CG. Besides that, the ALS individuals have no capability to adapt the autonomic nervous system when likened to the CG during therapy based on VR and their recovery.

Low heart rate variability from 10-s electrocardiograms is associated with development of non-alcoholic fatty liver disease.

Reduced heart rate variability (HRV) is reflective of autonomic imbalance. However, its impact on non-alcoholic fatty liver disease (NAFLD) is unknown. We investigated the association between 10-s HRV and incident NAFLD. A cohort of 154,286 Korean adults with no NAFLD at baseline were followed up. 10-s electrocardiograms were used to estimate two time-domain HRV, the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences in RR intervals (RMSSD). Hepatic steatosis (HS) and liver fibrosis were assessed using ultrasonography and the fibrosis-4 index (FIB-4). A total of 27,279 incident HS (median follow up of 4.2 years) and 1250 incident HS plus high FIB-4 (median follow up of 4.2 years) cases were identified at follow-up. The multivariable adjusted hazard ratios (aHRs) (95% confidence intervals [CIs]) in a model with time-dependent variables for incident HS, comparing the lowest quintile to the highest and reference quintile of the RMSSD, was 1.43 (1.37-1.49), and the corresponding HR for incident HS plus intermediate/high FIB-4 was 1.70 (1.35-2.15). Similarly, SDNN was inversely associated with incident HS and HS plus intermediate/high FIB-4. The results were similar using the NAFLD fibrosis score. Autonomic imbalance assessed by HRV may help to identify individuals at a high risk of HS and its progression and warrant further studies.

Heart rate complexity: An early prognostic marker of patient outcome after cardiac arrest.

OBJECTIVE: Early prognostication in comatose patients after cardiac arrest (CA) is difficult but essential to inform relatives and optimize treatment. Here we investigate the predictive value of heart-rate variability captured by multiscale entropy (MSE) for long-term outcomes in comatose patients during the first 24 hours after CA. METHODS: In this retrospective analysis of prospective multi-centric cohort, we analyzed MSE of the heart rate in 79 comatose patients after CA while undergoing targeted temperature management and sedation during the first day of coma. From the MSE, two complexity indices were derived by summing values over short and long time scales (CIs and CIl). We splitted the data in training and test datasets for analysing the predictive value for patient outcomes (defined as best cerebral performance category within 3 months) of CIs and CIl. RESULTS: Across the whole dataset, CIl provided the best sensitivity, specificity, and accuracy (88%, 75%, and 82%, respectively). Positive and negative predictive power were 81% and 84%. CONCLUSIONS: Characterizing the complexity of the ECG in patients after CA provides an accurate prediction of both favorable and unfavorable outcomes. SIGNIFICANCE: The analysis of heartrate variability by means of MSE provides accurate outcome prediction on the first day of coma.

Cluster headache: a single tertiary center study.

OBJECT: The characteristics of cluster headache (CH) patients in many countries and the diagnostic and therapeutic approach have been described in several publications, but so far no clinical data have been published from Turkey. MATERIAL METHODS: This is a cross-sectional retrospective study that includes all patients who were diagnosed with CH and referred to our headache clinic, Dokuz Eylül University Faculty of Medicine, Neurology Department from 1991 to January 2018. RESULTS: We included 114 patients (24 females and 90 males) in our study. The mean age at onset was 31.68 ± 12.72 (range 13-68). Eighty-six (78.18%) patients had episodic cluster headache (ECH) and 24 (21.82%) patients had chronic cluster headache (CCH). The age at onset was significantly higher in the patients with CCH than with ECH (p = 0.002). The most common location was orbitotemporal for both genders. The most common accompanying symptoms were lacrimation (80.73%). The male:female ratio in all patients was 3:7, 3.8:1 in those with CCH and 4:1 in those with ECH. Eighty-nine (87.25%) patients had prophylactic treatment and 60 of them received verapamil. CONCLUSION: In our study, some clinical features of our patients were similar to those of Europe and America or the Asian countries and some of them not. There are regional differences in cluster headache patients. With more awareness of cluster headache and research from many countries, clinical differences can be revealed more objectively in the future.

Facing successfully high mental workload and stressors: An fMRI study.

The present fMRI study aimed at highlighting patterns of brain activations and autonomic activity when confronted with high mental workload and the threat of auditory stressors. Twenty participants performed a complex cognitive task in either safe or aversive conditions. Our results showed that increased mental workload induced recruitment of the lateral frontoparietal executive control network (ECN), along with disengagement of medial prefrontal and posterior cingulate regions of the default mode network (DMN). Mental workload also elicited an increase in heart rate and pupil diameter. Task performance did not decrease under the threat of stressors, most likely due to efficient inhibition of auditory regions, as reflected by a large decrement of activity in the superior temporal gyri. The threat of stressors was also accompanied with deactivations of limbic regions of the salience network (SN), possibly reflecting emotional regulation mechanisms through control from dorsal medial prefrontal and parietal regions, as indicated by functional connectivity analyses. Meanwhile, the threat of stressors induced enhanced ECN activity, likely for improved attentional and cognitive processes toward the task, as suggested by increased lateral prefrontal and parietal activations. These fMRI results suggest that measuring the balance between ECN, SN, and DMN recruitment could be used for objective mental state assessment. In this sense, an extra recruitment of task-related regions and a high ratio of lateral versus medial prefrontal activity may represent a relevant marker of increased but efficient mental effort, while the opposite may indicate a disengagement from the task due to mental overload and/or stressors.

Standardized Autonomic Testing in Patients With Probable Radiation-Induced Afferent Baroreflex Failure.

Injury of the afferent limb of the baroreflex from neck radiation causes radiation-induced afferent baroreflex failure (R-ABF). Identification and management of R-ABF is challenging. We aimed to investigate the pattern of autonomic dysfunction on standardized autonomic testing in patients with probable R-ABF. We retrospectively analyzed all autonomic reflex screens performed at Mayo Clinic in Rochester, MN, between 2000 and 2020 in patients with probable R-ABF. Additional tests reviewed included ambulatory blood pressure monitoring, plasma norepinephrine, and thermoregulatory sweat test. We identified 90 patients with probable R-ABF. Median total composite autonomic severity score (range, 0-10) was 7 (interquartile range, 6-7). Cardiovascular adrenergic impairment was seen in 85 patients (94.4%), increased blood pressure recovery time after Valsalva maneuver in 71 patients (78.9%; median 17.4 seconds), and orthostatic hypotension in 68 patients (75.6%). Cardiovagal impairment was demonstrated by abnormal heart rate responses to deep breathing (79.5%), Valsalva ratio (87.2%), and vagal baroreflex sensitivity (57.9%). Plasma norepinephrine was elevated and rose appropriately upon standing (722-1207 pg/mL). Ambulatory blood pressure monitoring revealed hypertension, postural hypotension, hypertensive surges, tachycardia, and absence of nocturnal dipping. Blood pressure lability correlated with impaired vagal baroreflex function. Postganglionic sympathetic sudomotor function was normal in most cases; the most frequent thermoregulatory sweat test finding was focal neck anhidrosis (78.9%). Standardized autonomic testing in R-ABF demonstrates cardiovascular adrenergic impairment with orthostatic hypotension, blood pressure lability, and elevated plasma norepinephrine. Cardiovagal impairment is common, while sudomotor deficits are limited to direct radiation effects.

Social affiliation moderates the link between depressive symptoms and heart rate variability in healthy middle-aged and older individuals: An intensive ecologic momentary assessment study.

Depressive symptoms have been associated with lower cardiac autonomic control, thus contributing to cardiovascular diseases, especially among older adults. Interpersonal factors have been found to attenuate physiologic stress responses, but little is known about whether these factors (e.g., perceived affiliation) would moderate the relation of depressive symptoms and cardiovascular activation. The present research aimed to investigate the interplay of depressive symptoms and momentary-assessed interpersonal perceptions on cardiac vagal tone as indexed by heart rate variability (HRV). The sample consisted of 78 late middle-aged and older community-dwelling participants (48.7% male, mean age = 59.15 years). Participants reported on depressive symptoms and other personal characteristics by questionnaire. Perceptions of interpersonal affiliation, ambulatory HRV, and contextual variables were recorded using ecologic momentary assessment and portable electrocardiogram (ECG) monitoring device throughout 1 week (with a maximum of seven times daily). Multilevel analyses found that depressive symptoms were correlated with lower HRV, whereas momentary interpersonal perceptions of higher affiliation were associated with elevated HRV. A significant association was revealed between depressive symptoms and momentary affiliation perceptions on HRV. When individuals were involved in social interactions with higher affiliation, the effect of depressive symptoms on reducing HRV was attenuated. These findings suggested that the effects of subthreshold depressive symptoms on vagal control of the heart could be altered by the quality of interpersonal experiences.

Duration at high altitude influences the onset of arrhythmogenesis during apnea.

PURPOSE: Autonomic control of the heart is balanced by sympathetic and parasympathetic inputs. Excitation of both sympathetic and parasympathetic systems occurs concurrently during certain perturbations such as hypoxia, which stimulate carotid chemoreflex to drive ventilation. It is well established that the chemoreflex becomes sensitized throughout hypoxic exposure; however, whether progressive sensitization alters cardiac autonomic activity remains unknown. We sought to determine the duration of hypoxic exposure at high altitude necessary to unmask cardiac arrhythmias during instances of voluntary apnea. METHODS: Measurements of steady-state chemoreflex drive (SS-CD), continuous electrocardiogram (ECG) and SpO2 (pulse oximetry) were collected in 22 participants on 1 day at low altitude (1045 m) and over eight consecutive days at high-altitude (3800 m). SS-CD was quantified as ventilation (L/min) over stimulus index (PETCO2/SpO2). RESULTS: Bradycardia during apnea was greater at high altitude compared to low altitude for all days (p < 0.001). Cardiac arrhythmias occurred during apnea each day but became most prevalent (> 50%) following Day 5 at high altitude. Changes in saturation during apnea and apnea duration did not affect the magnitude of bradycardia during apnea (ANCOVA; saturation, p = 0.15 and apnea duration, p = 0.988). Interestingly, the magnitude of bradycardia was correlated with the incidence of arrhythmia per day (r = 0.8; p = 0.004). CONCLUSION: Our findings suggest that persistent hypoxia gradually increases vagal tone with time, indicated by augmented bradycardia during apnea and progressively increased the incidence of arrhythmia at high altitude.

Susceptibility of patients with chronic obstructive pulmonary disease to heart rate difference associated with the short-term exposure to metals in ambient fine particles: A panel study in Beijing, China.

Susceptibility of patients with chronic obstructive pulmonary disease (COPD) to cardiovascular autonomic dysfunction associated with exposure to metals in ambient fine particles (PM2.5, particulate matter with aerodynamic diameter ≤2.5 µm) remains poorly evidenced. Based on the COPDB (COPD in Beijing) panel study, we aimed to compare the associations of heart rate (HR, an indicator of cardiovascular autonomic function) and exposure to metals in PM2.5 between 53 patients with COPD and 82 healthy controls by using linear mixed-effects models. In all participants, the HR levels were significantly associated with interquartile range increases in the average concentrations of Cr, Zn, and Pb, but the strength of the associations differed by exposure time (from 1.4% for an average 9 days (d) Cr exposure to 3.5% for an average 9 d Zn exposure). HR was positively associated with the average concentrations of PM2.5 and certain metals only in patients with COPD. Associations between HR and exposure to PM2.5, K, Cr, Mn, Ni, Cu, Zn, As, and Se in patients with COPD significantly differed from those in health controls. Furthermore, association between HR and Cr exposure was robust in COPD patients. In conclusion, our findings indicate that COPD could exacerbate difference in HR following exposure to metals in PM2.5.