Parasympathetic Cardiac Control Research Articles

Autonomic contributions to attentional modulation of the cardiac defense response.

The cardiac defense response to aversive auditory stimulation is characterized by two acceleration/deceleration heart rate components. The first component is ascribed to attentional processes that facilitate detection and processing of potential threat, and the second one to protective actions. This study investigated attentional modulation of the cardiac defense response and the role of autonomic cardiac control therein. In 60 healthy subjects, the cardiac defense response was elicited, while electrocardiography, impedance cardiography and continuous blood pressure recordings were accomplished. Pre-ejection period represented sympathetic, heart rate variability parasympathetic, and systolic blood pressure sympathetic and parasympathetic, control. Half of the subjects performed a visual search task following the noise stimulus; the other half was exposed to the stimulus without any subsequent task. Task execution was associated with potentiation of the second heart rate acceleration/deceleration component of the defense response. Moreover, there was a greater systolic blood pressure decline during the second component. While pre-ejection period was unaffected by the task, the heart rate variability response was smaller overall in subjects performing the task. The findings suggest mediation of the first acceleration/deceleration component of the cardiac defense response by parasympathetic cardiac control; sympathetic and parasympathetic mechanisms contribute to the second component. While sympathetic control was unaffected by attentional demands, the potentiation of the cardiac defense response due to demands on external attention may relate to increased parasympathetic withdrawal.

The Influence of Perceived Discrimination on Heart Rate Variability in Young Black Adults

Introduction: Cardiovascular disease (CVD) is the leading cause of death in the United States, with a disproportional precedence in Black adults. Heart rate variability (HRV) is used to help predict future CVD, with lower HRV indicative of a compromised cardiovascular system. Prior evidence has suggested that experienced racial discrimination is associated with CVD risk. However, there is limited information regarding experienced racial discrimination on HRV in young Black adults. Purpose/hypothesis: The purpose of this study was to determine whether personal-level and group-level racial discrimination was associated with worse HRV in young Black adults. Methods: Black adults aged 18-25 (n=18, 44.45% female) volunteered to participate in this study, arriving at the lab at 7am in a fasted state. Following 30 minutes of rest, HRV measures were assessed using a SphygmoCor 3-lead ECG in a supine position. The HRV measure included the standard deviation of all R-R intervals (SDNN), the mean number of times an hour successive NN intervals exceeds 50ms (pNN50), the root mean square of successive differences (RMSSD), the low-frequency (LF) power domain, high-frequency (HF) power domain, and their ratio (LF:HF). Participants were given a perceived racial discrimination questionnaire that assessed personal-level and group-level discrimination. Pearson correlations were used to analyze the association between perceived racial discrimination measures and HRV measures. Results: In Black males, perceived personal-level racial discrimination was negatively associated with sympathetic activity (LF, R2 = -0.704, p = 0.023) and sympathovagal balance (LF:HF, R2 = -0.749, p = 0.013), and positively associated with parasympathetic activity (HF, R2 = 0.704, p = 0.023). Perceived group-level racial discrimination was not associated with HRV measures. Furthermore, perceived racial discrimination was not associated with HRV in Black females. Conclusion: Although decreased HRV has been associated with increased risk for CVD, higher HRV has been shown to be associated with left ventricular mass in Black adults. Therefore, HRV implications may be dependent on social determinants of health and other covariates that are associated with race/ethnicity. In the current study, higher HRV was observed in Black males who reported higher personal-level discrimination, which may be an important factor in sympathetic and parasympathetic cardiac control and CVD risk. Given our preliminary findings, more research is warranted that investigates the impact of racial identity, resiliency, coping, and healthy lifestyle behaviors on mitigating the detrimental impact of perceived racial discrimination on the cardiovascular health of young Black adults. Summer Undergraduate Research Fellowship Recipient from the American Physiological Society. This is the full abstract presented at the American Physiology Summit 2024 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.

Electric Burn Injury and Cardiac Autonomic Function

Electrical injuries are a common form of mechanical trauma that can cause significant damage to the skin and underlying tissues, as well as potentially affect other systems of the body, including the cardiovascular system. Electric burn injury can affect cardiac autonomic function, potentially leading to arrhythmias and heart failure. The autonomic nervous system plays a critical role in regulating cardiac function, acting as the primary regulator of heart rate and contractility. The balance between the two systems, sympathetic and parasympathetic, is essential for optimal cardiovascular function and can be assessed through measures of cardiac autonomic function. The most commonly utilized method is using the electrocardiogram (ECG) in combination with the impedance cardiogram (ICG). The pre-ejection period (PEP) can be extracted from ECG during the left ventricular ejection as a measure of cardiac sympathetic control, and the respiratory sinus arrhythmia can be extracted from ECG during respiration as a measure of cardiac parasympathetic control. This literature review explores the current understanding of how electric burn injury affects cardiac autonomic function and its potential influence on cardiac function. It also emphasize the need of further research to understand the precise mechanisms involved in the effects of electric burn injury on cardiac autonomic function and to develop effective treatment strategies to prevent adverse cardiovascular outcomes.

High-trait anxious individuals show positive relationship between HRV and threat vigilance.

Selectively attending to threat-related stimuli in the environment, known as threat bias (TB), is a prominent feature of anxiety. Individuals with high anxiety also tend to show lower heart rate variability (HRV), a reflection of reduced parasympathetic cardiac control. Previous investigations have established associations between low HRV and various attentional processes that facilitate attention to threat, though these have primarily been conducted among non-anxious individuals. The current analysis, derived from a larger TB modification study, examined the relationship between TB and HRV among a young, nonclinical sample of individuals with either high or low trait anxiety (HTA, LTA, respectively; Mage =25.8, SD=13.2, 61.3% female). Consistent with expectations, HTA (β=-.18, p=.087) trended toward an association with higher threat vigilance. A significant moderation effect showed the relationship between HRV and threat vigilance was influenced by TA (β=.42, p=.004). Simple slopes analysis revealed that for the LTA group, lower HRV trended toward higher threat vigilance (p=.123), consistent with expectations. However, this relationship was unexpectedly reversed for the HTA group, for whom higher HRV was a significant predictor of higher threat vigilance (p=.015). These results are interpreted within a cognitive control framework, in which regulatory ability, as assessed via HRV, may influence which cognitive strategy is employed when encountering threatening stimuli. Results suggest that HTA individuals with greater regulatory ability may employ a contrast avoidance mechanism, while those with reduced regulatory ability engage in cognitive avoidance.

Effect of Cognitive-Behavioral Therapy on Nocturnal Autonomic Activity in Patients with Fibromyalgia: A Preliminary Study.

Objective: fibromyalgia is a complex chronic pain syndrome characterized by widespread musculoskeletal pain, insomnia and autonomic alterations. Cognitive-behavioral therapy (CBT) is regarded as a promising treatment in fibromyalgia, but its impact on autonomic function remains uncertain. In this research, we studied the effect of CBT on autonomic functions in fibromyalgia. Methods: Twenty-five participants underwent overnight polysomnographic recordings before and after CBT programs focused on pain (CBT-P) or a hybrid modality focused on pain and insomnia (CBT-C). Sleep quality, daily pain, depression and anxiety were assessed by self-reported questionnaires. We analyzed heart rate variability (HRV) using high-frequency power (HF) as a marker for parasympathetic activity, and low-frequency power (LF) and the LF/HF ratio as relative sympathetic markers during wakefulness and at each sleep stage. Results: After treatment, 14 patients (/25, 58.0%) reported improvement in their sleep: 6 in the CBT-P condition (/12, 50%), and 8 in the CBT-C condition (/13, 61.5%). We found that, regardless of the type of CBT, patients who reported improvement in sleep quality (n = 14, 58%) had an increase in HF during stages N2 (p < 0.05) and N3 (p < 0.05). These changes were related to improvement in sleep quality (N2, r = −0.43, p = 0.033) but not to pain, depression or anxiety. Conclusions: This study showed an improvement in parasympathetic cardiac control during non-rapid-eye-movement sleep following CBT in fibromyalgia participants who reported better sleep after this therapy. CBT may have a cardio-protective effect and HRV could be used as a sleep monitoring tool in fibromyalgia.

Molecularly defined circuits for cardiovascular and cardiopulmonary control.

The sympathetic and parasympathetic nervous systems powerfully regulate internal organs1, but the molecular and functional diversity of their constituent neurons and circuits remains largely unknown. Here we use retrograde neuronal tracing, single-cell RNA sequencing, optogenetics, and physiological experiments to dissect the cardiac parasympathetic control circuit in mice. We show that cardiac-innervating neurons in the brainstem nucleus ambiguus (Amb) are comprised of two molecularly, anatomically, and functionally distinct subtypes. One we call ACV (ambiguus cardiovascular) neurons (~35 neurons per Amb), define the classical cardiac parasympathetic circuit. They selectively innervate a subset of cardiac parasympathetic ganglion neurons and mediate the baroreceptor reflex, slowing heart rate and atrioventricular node conduction in response to increased blood pressure. The other, ACP (ambiguus cardiopulmonary) neurons (~15 neurons per Amb) innervate cardiac ganglion neurons intermingled with and functionally indistinguishable from those innervated by ACV neurons, but surprisingly also innervate most or all lung parasympathetic ganglion neurons; clonal labeling shows individual ACP neurons innervate both organs. ACP neurons mediate the dive reflex, the simultaneous bradycardia and bronchoconstriction that follows water immersion. Thus, parasympathetic control of the heart is organized into two parallel circuits, one that selectively controls cardiac function (ACV circuit) and another that coordinates cardiac and pulmonary function (ACP circuit). This new understanding of cardiac control has implications for treating cardiac and pulmonary diseases and for elucidating the control and coordination circuits of other organs.

Parasympathetic cardiac control during attentional focus and worry in major depressive disorder

Worry, which refers to uncontrollable chains of thoughts and images with negative affective load, is a transdiagnostic symptom of various mental disorders including major depressive disorder (MDD). Current theories relate excessive worry to deficient top-down control of automatically occurring perseverative thinking. This study investigated parasympathetic cardiac control in MDD in the context of worry and cognitive control. Heart rate variability (HRV) was recorded, in the high frequency (HF) and low frequency (LF) bands, in 36 MDD patients and 36 healthy controls while they performed a breathing focus task. The task included two phases during which participants' ability to concentrate on their breathing was assessed before and after an instructed worry phase. In addition to higher self-reported worry, MDD patients exhibited lower HF and LF HRV at rest, and lower LF HRV during the task than controls. MDD was also associated with impaired breathing concentration ability, more negative and neutral thought intrusions, more negative mood during breathing focus and increased stress during instructed worry. In the total sample, LF HRV correlated negatively with self-reported worry and negative thought intrusions, and positively with mood ratings. The reduction of HRV confirms the notion of low parasympathetic cardiac control in MDD. Moreover, low HRV represents a correlate of blunted prefrontal activity and impaired cognitive control that characterize the disorder. Impaired cognitive control may exacerbate worry, which is in turn involved in the genesis of aversive emotional states and maintenance of MDD.

Acute effects of oral delta-9-tetrahydrocannabinol (THC) on autonomic cardiac activity and their relation to subjective and anxiogenic effects.

Cannabis is the most commonly used psychotropic drug in the United States, after alcohol. Despite its apparent sedative and calming effects, cannabis and its main psychoactive constituent, ∆9 -tetrahydrocannabinol (THC) can produce serious adverse effects including tachycardia and anxiety. These effects can be especially pronounced in women, who remain underrepresented in clinical cannabinoid research. The present study is one of the first to characterize the effects of single doses of oral THC on autonomic nervous system function in healthy adult women. Occasional female cannabis users participated in three laboratory sessions in which they received oral THC (7.5 and 15mg) and placebo. Autonomic measures included heart rate (HR), blood pressure (BP), pre-ejection period (PEP) a measure of cardiac sympathetic functioning, and high frequency heart rate variability (HF-HRV) a measure of parasympathetic cardiac control. Autonomic responses were examined in relation to subjective drug effects. THC dose-dependently increased HR, decreased HF-HRV, and increased ratings of feeling a drug effect, cannabis-like intoxication, and anxiety. Although the drug did not significantly affect BP or PEP, HR was negatively related to both PEP and HF-HRV. HF-HRV, the measure of parasympathetic activity, was significantly negatively related to subjective measures of cannabis intoxication (but not anxiety) at the 15mg dose only. PEP was not significantly related to any subjective measure. These results extend our knowledge of the autonomic effects of THC in relation to subjective drug experience. This and future studies will help us to understand risk factors related to cannabis use.

Transcytosis within PVN capillaries: a mechanism determining both hypertension-induced blood-brain barrier dysfunction and exercise-induced correction.

Although hypertension disrupts the blood-brain barrier (BBB) integrity within the paraventricular nucleus of hypothalamus (PVN) and increases the leakage into the brain parenchyma, exercise training (T) was shown to correct it. Since there is scarce and contradictory information on the mechanism(s) determining hypertension-induced BBB deficit and nothing is known about T-induced improvement, we sought to evaluate the paracellular and transcellular transport across the BBB within the PVN in both conditions. Spontaneously hypertensive rats (SHR) and WKY submitted to 4-wk aerobic T or sedentary (S) protocol were chronically catheterized for hemodynamic recordings at rest and intra-arterial administration of dyes (Rhodamine-dextran 70 kDa + FITC-dextran 10 kDa). Brains were harvesting for FITC leakage examination, qPCR evaluation of different BBB constituents and protein expression of caveolin-1 and claudin-5, the main markers of transcytosis and paracellular transport, respectively. Hypertension was characterized by increased arterial pressure and heart rate, augmented sympathetic modulation of heart and vessels, and reduced cardiac parasympathetic control, marked FITC extravasation into the PVN which was accompanied by increased caveolin-1 gene and protein expression, without changes in claudin-5 and others tight junctions' components. SHR-T vs. SHR-S showed a partial pressure reduction, resting bradycardia, improvement of autonomic control of the circulation simultaneously with correction of both FITC leakage and caveolin-1 expression; there was a significant increase in claudin-5 expression. Caveolin-1 content was strongly correlated with improved autonomic control after exercise. Data indicated that within the PVN the transcytosis is the main mechanism governing both hypertension-induced BBB leakage, as well as the exercise-induced correction.

Reduced Cell Excitability of Cardiac Postganglionic Parasympathetic Neurons Correlates With Myocardial Infarction-Induced Fatal Ventricular Arrhythmias in Type 2 Diabetes Mellitus

ObjectiveWithdrawal of cardiac vagal activity is considered as one of the important triggers for acute myocardial infarction (MI)-induced ventricular arrhythmias in type 2 diabetes mellitus (T2DM). Our previous study demonstrated that cell excitability of cardiac parasympathetic postganglionic (CPP) neurons was reduced in T2DM rats. This study investigated whether cell excitability of CPP neurons is associated with cardiac vagal activity and MI-induced ventricular arrhythmias in T2DM rats.MethodsRat T2DM was induced by a high-fat diet plus streptozotocin injection. MI-evoked ventricular arrhythmia was achieved by surgical ligation of the left anterior descending coronary artery. Twenty-four-hour, continuous ECG recording was used to quantify ventricular arrhythmic events and heart rate variability (HRV) in conscious rats. The power spectral analysis of HRV was used to evaluate autonomic function. Cell excitability of CPP neurons was measured by the whole-cell patch-clamp technique.ResultsTwenty-four-hour ECG data demonstrated that MI-evoked fatal ventricular arrhythmias are more severe in T2DM rats than that in sham rats. In addition, the Kaplan-Meier analysis demonstrated that the survival rate over 2 weeks after MI is significantly lower in T2DM rats (15% in T2DM+MI) compared to sham rats (75% in sham+MI). The susceptibility to ventricular tachyarrhythmia elicited by programmed electrical stimulation was higher in anesthetized T2DM+MI rats than that in rats with MI or T2DM alone (7.0 ± 0.58 in T2DM+MI group vs. 3.5 ± 0.76 in sham+MI). Moreover, as an index for vagal control of ventricular function, changes of left ventricular systolic pressure (LVSP) and the maximum rate of increase of left ventricular pressure (LV dP/dtmax) in response to vagal efferent nerve stimulation were blunted in T2DM rats. Furthermore, T2DM increased heterogeneity of ventricular electrical activities and reduced cardiac parasympathetic activity and cell excitability of CPP neurons (current threshold-inducing action potentials being 62 ± 3.3 pA in T2DM rats without MI vs. 27 ± 1.9 pA in sham rats without MI). However, MI did not alter vagal control of the ventricular function and CPP neuronal excitability, although it also induced cardiac autonomic dysfunction and enhanced heterogeneity of ventricular electrical activities.ConclusionThe reduction of CPP neuron excitability is involved in decreased cardiac vagal function, including cardiac parasympathetic activity and vagal control of ventricular function, which is associated with MI-induced high mortality and malignant ventricular arrhythmias in T2DM.

Control of Heart Rate by Nucleus Ambiguus Cardiovagal Neurons

Heart rate is a well-established indicator of overall health and well-being, yet little is known about the neurons that control it. Although the heart has its own pacemaker, heart rate is largely regulated by the interplay between sympathetic activities (via sympathoexcitatory neurons) and parasympathetic activities (via cardiac vagal preganglionic neurons (CVNs)). The nucleus ambiguus (nAmb), a region in the medullary reticular formation of the brainstem, is a major center of parasympathetic cardiac control and houses the majority of CVNs, along with other neurons that control respiratory functions (bronchoconstriction, bronchosecretion) and upper airway and esophageal muscles. Because of the diversity of neuron types in the nAmb, it is challenging to isolate CVNs for study, which greatly limits what we know about their gene expression, synaptic circuitry, and specific roles in cardiac function. To address these issues, we characterized cardiovagal neurons based on transcriptome-wide mRNA expression, synaptic circuitry, and sufficiency for heart rate control. Our single-cell transcriptomics analysis of 235 nAmb neurons pointed to three molecularly distinct neuron subtypes (marked by the genes Crhr2, Vipr2, and Tbx3) in the nAmb, which we validated and anatomically mapped by in situ detection of marker transcripts. We then used marker-driven genetic technology to fluorescently label the axon projections of Tbx3 nAmb neurons and imaged them in optically cleared heart samples. Our results show that these neurons innervate multiple sites in the atria and ventricles, consistent with multiple roles in cardiac function. Similar synaptic circuitry studies of the Crhr2 nAmb and Vipr2 nAmb neurons showed that they innervate the esophagus and larynx, respectively, but do not innervate the heart. Furthermore, using an intersectional optogenetics approach to specifically manipulate the activity of nAmb neuron subtypes in vivo, we have shown that activating the Tbx3 nAmb neurons in both freely behaving and anesthetized mice dramatically and immediately decreases heart rate (from 430 bpm to 160 bpm) as determined via EKG readings, whereas activating other subtypes of nAmb neurons did not affect heart rate. This effect on heart rate was abolished by administration of atropine, a muscarinic receptor antagonist. Together, these studies not only highlight the impact of Tbx3 nAmb neurons on heart rate, but also reveal a distinct molecular, anatomical, and functional organization within the nAmb.

Impact of acute partial-body cryostimulation on cognitive performance, cerebral oxygenation, and cardiac autonomic activity

We assessed the effects of a 3-min partial-body cryostimulation (PBC) exposure—where the whole body is exposed to extreme cold, except the head—on cognitive inhibition performance and the possible implications of parasympathetic cardiac control and cerebral oxygenation. In a randomized controlled counterbalanced cross-over design, eighteen healthy young adults (nine males and nine females) completed a cognitive Stroop task before and after one single session of PBC (3-min exposure at − 150 °C cold air) and a control condition (3 min at room temperature, 20 °C). During the cognitive task, heart rate variability (HRV) and cerebral oxygenation of the prefrontal cortex were measured using heart rate monitoring and near-infrared spectroscopy methods. We also recorded the cerebral oxygenation during the PBC session. Stroop performance after PBC exposure was enhanced (562.0 ± 40.2 ms) compared to pre-PBC (602.0 ± 56.4 ms; P < 0.042) in males only, accompanied by an increase (P < 0.05) in HRV indices of parasympathetic tone, in greater proportion in males compared to females. During PBC, cerebral oxygenation decreased in a similar proportion in males and females but the cerebral extraction (deoxyhemoglobin: ΔHHb) remained higher after exposure in males, only. These data demonstrate that a single PBC session enhances the cognitive inhibition performance on a Stroop task in males, partly mediated by a greater parasympathetic cardiac control and greater cerebral oxygenation. The effects of PBC on cognitive function seem different in females, possibly explained by a different sensitivity to cold stimulation.

Diurnal variation of heart rate variability as a physiological index of mood and emotion regulation processes in Major Depression and Borderline Personality Disorder

BackgroundHeart rate variability (HRV), a measure of autonomic nervous system activity, has been studied in a number of psychiatric disorders during the resting state but evidence on its circadian patterns in Major Depressive Disorder (MDD) and Borderline Personality Disorder (BPD) is scarce. We sought to identify and differentiate HRV circadian patterns in MDD, BPD and healthy controls (HC) while exploring potential physiological mechanisms associated with mood and emotion dysregulation. Methods24-Hour electrocardiographic recordings were obtained from fifty subjects (16 HC, 18 BPD, 16 MDD). HRV was calculated during sleep and wake periods. Associations with mood and affect measures, and with cognitive emotion regulation strategies and self-reported difficulties in emotion regulation (DERS) were examined. Participant’s resilience traits were explored in relation to mood and emotion regulation variables. ResultsLower diurnal measures of HRV (i.e, RMSSD and HF) were observed in MDD subjects compared to HCs. Decreased HF was observed during wake vs. sleep in MDD patients. HAM-D and negative affect scores negatively correlated with HRV in MDD and BPD respectively. MDD and BPD exhibited a positive relationship between the implementation of emotion regulation strategies and HRV compared to HC. Increased resilience was associated with lower HAM-D and DERS scores in BPD and HC. ConclusionHRV alterations characterized by low diurnal cardiac parasympathetic control constitute a potential trait biomarker of major depression and psychiatric vulnerability to depressive episodes in BPD. HRV anomalies in MDD may persist during clinical remission. Diurnal HRV may represent a psychophysiological index of mood and emotion regulation.

Parasympathetic cardiac control and attentional focus in trait worry

Trait worry refers to a tendency toward increased vigilance to threat and reduced tolerance of uncertainty. While it has been established as a risk factor of general morbidity, knowledge about autonomic regulation in trait worry remains scarce. This study investigated parasympathetic cardiac control in trait worry, in the context of attentional focus. Healthy groups with high and low worry were selected using the Penn State Worry Questionnaire (n = 40 per group). Heart rate variability (HRV) was recorded in the high frequency (HF) and low frequency (LF) bands while participants performed a breathing focus task. The task included a phase of instructed worry and two phases during which participants´ ability to concentrate on their breathing was assessed. As compared to the low worry group, the high worry group exhibited lower HRV in the LF band during both breathing focus phases and smaller reduction of LF HRV during instructed worry. HF HRV did not differ between groups. High worry was associated with impaired ability to concentrate on breathing and more intrusive thoughts. In the total sample, negative intrusions correlated negatively with LF HRV during the first breathing focus phase and LF HRV reactivity. Instructed worry led to greater perceived stress and deterioration of mood in high worry participants. Reduced LF HRV reflects blunted parasympathetic cardiac control in trait worry, associated with elevated risk of poor health outcomes. In addition, it might represent a psychophysiological correlate of reduced cognitive inhibition, which interferes with attentional focus and impedes control of threat processing and perseverative thinking.

Folic Acid Supplementation Increases Cardiac Parasympathetic Modulation of Heart Rate in Habitually Endurance Trained and Untrained Middle‐Aged Men

IntroductionAgeing is associated with decreased, and exercise training increased, parasympathetic modulation of heart rate (HR). Cardiac parasympathetic control has prognostic significance in cardiac disease, but the mechanisms remain unclear. Nitric oxide (NO) is thought to play an important role, both at the level of the sinoatrial node and through modulation of autonomic control of HR. Folic acid (FA) increases vascular NO levels. The modulatory effects of FA, ageing and exercise training on autonomic control of HR, are unknown. Thus, we tested the hypothesis that FA supplementation would increase cardiac parasympathetic modulation of HR in habitually trained and untrained middle‐aged men, with FA and exercise training eliciting greater increases than either exercise or FA alone.MethodsTwo groups of healthy, normotensive, age‐matched (55±3 years; overall mean±SEM), habitually endurance trained (n=14; VO2peak 49±1 ml/kg/min; MAtr;) and untrained (n=14; 37±1 ml/kg/min; MAun) men were studied. A comparator group of young (26±1 years) untrained (n=14; 50±1 ml/kg/min; YMun) men were also studied. Heart rate variability (HRV), an index of cardiac modulation of HR, was recorded during 7 minutes of supine rest using lead II of an ECG, both before and after 4 weeks of FA supplementation (5mg/day). Fast Fourier frequency domain measures were determined: high frequency (HF), low frequency (LF), and very LF (VLF). Due to skewness, HF, LF and VLF data were log transformed. LF:HF ratio and total (VLF+LF+HF) HRV were calculated. Circulating levels of folate, plasma nitrite, a stable metabolite of NO, were determined.ResultsAt baseline, HFlog, LFlog and Total HRV did not differ (p&gt;0.05) between MA groups, but were higher in YMun (p&lt;0.05). VLFlog, LF:HF, and folate levels did not differ (p&gt;0.05) between groups. Resting HR was lower (p&lt;0.05) in MAtr versus MAun, but did not differ (p&gt;0.05) between MAun and YMun. Nitrite levels were highest (p&lt;0.05) in MAtr.Post‐FAWithin‐groups, HFlog, LFlog, Total HRV and folate levels were increased (p&lt;0.05). LF:HF, VLFlog, HR and nitrite levels were unaltered (p&lt;0.05). Between‐groups, HFlog, LFlog, and Total HRV remained similar (0&gt;0.05) between MA groups, and higher (p&lt;0.05) in YMun. VLFlog, LF:HF, and folate levels did not differ (p&gt;0.05) between groups. Resting HR remained lower (p&lt;0.05) in MAtr versus MAun, and similar (p&gt;0.05) between MAun and YMun. Nitrite levels were higher (p&lt;0.05) in MAtr versus YMun.ConclusionWe report similar HF, LF and Total HRV, and lower resting HR, in trained versus untrained MA men. After four‐weeks of FA supplementation, HF, LF and Total HRV were increased, and HR unaltered, in both groups. These findings suggest cardiac parasympathetic control of HR does not differ between endurance trained and untrained MA men. In contrast, short‐term FA supplementation augments cardiac parasympathetic modulation in both groups. Further, exercise training and FA do not confer additive effects. Given the clinical significance of cardiac parasympathetic modulation of HR, FA may independently provide protective cardiac autonomic effects with healthy ageing in men.Support or Funding InformationThe research was supported by the National Institute for Health Research (NIHR) Leicester BRC.

Cardiovagal baroreflex gain relates to sensory loss after spinal cord injury.

Spinal cord injury (SCI) leads to autonomic nervous system damage, resulting in loss of sympathetic control to the vasculature and the heart proportional to injury level. Given maintained cardiac parasympathetic control, we hypothesized that SCI demonstrates a compensatory, higher baroreflex gain compared to able-bodied that relates to injury level (neurological and/or sensory). We compared baroreflex gain (average and across 10-20, 20-30, and 30-40mmHg input stimuli) derived from neck chamber technique in SCI (N=29; neurological level C1-T10, sensory zone of partial preservation C4-S4/5; ≤2yrs since injury) and able-bodied (N=14). Average gain tended to be higher in able-bodied compared to SCI (p=0.06), primarily due to higher gains at 10-20 and 20-30mmHg (p=0.03, p=0.06). In SCI, although gain was not related to neurological level, average gain and gain at 10-20mmHg was related to sensory zone of partial preservation and resting RR-interval (all p<0.02). Multiple regression showed that both sensory level and RR-interval were strongly predictive of average baroreflex gain (r2=0.41, p<0.01) and gain at 10-20mmHg (r2=0.51, p<0.01); gain decreased with higher sensory zone of partial preservation and lower resting RR-interval. Moreover, gain was significantly lower in those with high sensory level compared to both able-bodied (average gain and gain at 10-20 and 20-30mmHg p<0.01) and those with low level injury (all p<0.05). In SCI, sensory zone of partial preservation is more predictive of gain than neurological level. This might reflect that those with high level sensory injuries may have the lowest likelihood of intact cardiac sympathetic innervation and therefore lesser cardiac vagal responsiveness due to vagal-sympathetic interactions.

Heart rate variability analysis and cardiac dysautonomia in ischemic stroke patients

ObjectivesAutonomic nervous system dysfunction after ischemic stroke predisposes to cardiovascular complications. We aimed to investigate cardiac autonomic activity in ischemic stroke patients using heart rate variability analysis, illustrating the sympathovagal balance at different sympathetic and parasympathetic activation tests. Patients and methodsWe studied the dynamics of the linear and non-linear heart rate variability parameters in 31 left and 40 right middle cerebral artery ischemic stroke patients in rest condition and during autonomic activation tests (handgrip, standing, deep breathing and Valsalva maneuver). Data were compared with 30 age- and sex-matched healthy controls. ResultsWe found different responses after autonomic activation tests in stroke patients depending on the cortical lateralization of the ischemic lesion. In resting state, left hemisphere stroke patients presented enhanced parasympathetic modulation of the heart rate (higher values for RMSSD, pNN50, HF and SD1, p < 0.05), comparing to right hemisphere stroke patients. This second group displayed a reduced cardiac parasympathetic control in resting state and during autonomic activation tests (handgrip and standing tests) compared to the left hemisphere stroke group and controls. Non-linear parameters SD1 and DFA α1 showed a decrease of variability and complexity of the heart rate in right hemisphere stroke patients, ameliorated during vagal activation tests. ConclusionTo prevent possible complications with vital risk, assessment of cardiovascular autonomic activity becomes a necessary stage in stroke patient management, facilitating immediate implementation of preventive and therapeutic strategies. Heart rate variability analysis in resting state and during autonomic activation tests allows identifying patients prone to sympathetic hyperactivity. New therapeutic perspectives for stroke management may emerge founded on the modulation of the autonomic nervous system.

O-02 Study of the cortical control of the cardiac autonomic nervous system using intracerebral electrical stimulations

Background The activity of the cardiac autonomic nervous system is modulated by cortical regions. The function of the insula in the cardiac autonomic control has been widely described in humans, but the roles of the other regions of the central autonomic network (such as the ventromedial prefrontal cortex, the amygdala or the anterior cingulate cortex) remain unclear. In order to better understand the role of the central autonomic network in the cardiac autonomic control, we studied the impact of intracerebral electrical stimulation of the insular cortex, the anterior cingulate cortex, the orbito-frontal cortex and the amygdala on the heart rate variability. Methods We included 36 epileptic patients undergoing stereoencephalogram who were stimulated by trains (except for the amygala, which was stimulated by shocks). The vagal tone was quantified by computing the heart rate variability in high frequencies (HFV Index), before and after theelectrical stimulations. Results A decrease in HFVI was observed after the stimulation of the postero-superior region of the insula bilaterally, but not in the inferior and antero-superior parts of the insula, whereas an increase of HFVI was only observed after the stimulation of the left orbito-frontal cortex. Conclusions Our results emphasize the role of the left orbito frontal cortex in the cardiac parasympathetic control. In the insula, the postero-superior part seems to be the main insular area involved in cardiac autonomic control.

Cardiovagal baroreflex gain relates to sensory but not neurological level of spinal cord injury

The arterial baroreflex is a primary regulator of autonomic outflow to effectively regulate acute blood pressure changes. After a spinal cord injury (SCI), damage to the autonomic nervous system results in cardiovascular dysregulation. Higher level of injury results in greater loss of sympathetic control, while cardiac parasympathetic control remains intact regardless of injury level. Thus, it is possible that those with high level SCI, and hence extensive sympathetic disruption, will require greater cardiac parasympathetic compensation to control blood pressure. However, the effect of an SCI on cardiovagal baroreflex gain remains unclear. Baroreflex control of blood pressure in those with SCI has been reported to be greater, lesser, and no different compared to able‐bodied individuals. Moreover, the effect of injury level on baroreflex gain remains unclear as most studies that examined the effect of lesion level treated it as a discrete variable – high, usually cervical level lesions, and low, usually thoracic level lesions. Therefore, we assessed baroreflex sensitivity using the neck chamber techniques in those with SCI (N = 29) across a range of injury levels (neurological level of injury C1 – T10, sensory score C4 – S4/5), within 2 years of injury, and compared them to able‐bodied (N = 14). Injury level was assessed by both neurological level of injury and sensory score. We assessed baroreflex gain during 5 trials of 4 levels of neck chamber pressure (corresponding to −15, −25, −35, and −45 mmHg). We found no difference in baroreflex gain between those with SCI and able‐bodied (p&gt;0.1). Neurological level of injury was not correlated to baroreflex gain, but sensory score and resting RR‐interval were (r = 0.47, p&lt;0.01; r = 0.57, p&lt;0.01). Multiple regression showed that both sensory score and resting RR‐interval were strongly predictive of baroreflex gain (r2 = 0.47, p&lt;0.01): gain increased with lower sensory score and higher resting RR‐interval. Moreover, baroreflex gain was not different between those with high and low neurological level of injury; but higher in those with lower compared to higher sensory score (both p&lt;0.01). Hence, sensory score is more predictive of baroreflex gain than the widely used neurological level of injury. This might be understood in the context of vagal‐sympathetic accentuated antagonism: those with high level injuries have the lowest likelihood of intact cardiac sympathetic innervation depressing cardiac vagal responsiveness.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Using acoustic features of mothers’ infant-directed speech to predict changes in infant biobehavioral state

Infant directed speech is marked by exaggerated frequency modulation and strong high frequency power, features that may provide physiological cues for mobilization or calming (Porges and Lewis, 2010; Kolacz et al., 2018). We examined whether these features predicted changes in infant biobehavioral state during the Still Face Paradigm, a stressor in which the mother withdraws and reinstates social cues. 98 mother-infant dyads participated when infants were 4-8 months old. Infant heart rate and respiratory sinus arrhythmia (a measure of cardiac parasympathetic control) were derived from an electrocardiogram (ECG). Infant behavioral distress was measured by vocal, facial, and body movement distress. Mothers’ vocalizations were measured using spectral analysis within designated frequency bands and modulation using a 2-dimensional fast Fourier transform of the audio spectrogram. Maternal frequency modulation predicted decreases in infant heart rate (p = .030), mid-frequency acoustic power (500–5000 Hz) predicted increases in cardiac parasympathetic regulation in infants with low parasympathetic tone (p = .024), and high frequency power predicted increases in infant behavioral distress in infants who were not initially distressed (p = .011). These results suggest that mothers’ vocal frequency band power and modulation may be aspects of infant-directed speech that are relevant for regulating infant biobehavioral state.