Baroreceptor Function Research Articles

A Functional Neurological Approach to Postural Orthostatic Tachycardia Syndrome.

Event Abstract Back to Event A Functional Neurological Approach to Postural Orthostatic Tachycardia Syndrome. TJ Graber1* 1 Fulda Family Chiropractic, PA, United States A review of cases of medically diagnosed Postural Orthostatic Tachycardia Syndrome (POTS) as treated from a functional neurological basis. 10 patients presented with medically diagnosed POTS and were treated medically with some reductions in heart rate, but no positive changes in symptoms. 7 patients were adolescent females age 12-17, 1 patient was a male age 17 and 2 patients were females age 30-36. Symptoms presented as headache, migraine, fatigue, fever, skin rashes, constipation, abdominal cramping/pain, behavioral changes, short term memory issues. Findings after an extensive neurological exam to demonstrate areas of neurological compromise when compared to the corresponding area on the opposite side. Included frontal lobe, parietal lobe, temporal lobe, cerebellum, mesencephelon, pontine, medulla areas; baroreceptor function for heart rate, Intermediolateral column. Assessing the areas mentioned through a comparative neurological exam: 9 out of ten POTS patients demonstrated right frontal, right parietal, right mesencephalon, left cerebellum neurologic compromise. One patient presented opposite following a concussion which during treatment reversed at visit 6 and she then presented the same as the other 9 POTS patients. 10 out of the 10 patients had altered baroreceptor responses to carotid sinus pressure while listening with stethoscope. The response consisted of no change to slightly decreased with no rebound heart rate increase. Treatment consisted of unilateral dynamic left body movements, left vestibular stimulation, balance training on a balance beam, parietal and frontal lobe eye exercises. 10 out of 10 reported improvement in symptoms and demonstrated decreased heart rate change with a change in body position from lying to standing to below 10 beats per minute change. 9 out of 10 patients were able to resume their activities of daily living and full classroom time without complication with improvement in all the symptoms. 1 adolescent female patient had improved activities of daily living, but no change in headache. The only improvement in headache came from amitriptyline which then made her heart rate increase more with changes in posture. Commitment to home exercises were also less than prescribed. In Discussion: Functional Neurology and Rehabilitation is shown to be a very effective therapy in treating individuals with POTS. Acknowledgements Limited abstract version. Thank the Carrick Institute for giving the knowledge to treat these dynamic patients and improving lives beyond what I thought was my potential. Keywords: POTS, Postural Orthostatic Tachycardia Syndrome, Functional Neurology, baroreceptors, Amitriptyline Conference: International Symposium on Clinical Neuroscience: Clinical Neuroscience for Optimization of Human Function, Orlando, United States, 7 Oct - 9 Oct, 2016. Presentation Type: Citation: Graber T (2016). A Functional Neurological Approach to Postural Orthostatic Tachycardia Syndrome.. Front. Neurol. Conference Abstract: International Symposium on Clinical Neuroscience: Clinical Neuroscience for Optimization of Human Function. doi: 10.3389/conf.fneur.2016.59.00099 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Jul 2016; Published Online: 07 Sep 2016. * Correspondence: Dr. TJ Graber, Fulda Family Chiropractic, PA, Fulda, MN, 56131, United States, drtjgraber@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers TJ Graber Google TJ Graber Google Scholar TJ Graber PubMed TJ Graber Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Tonically Active cAMP-Dependent Signaling in the Ventrolateral Medulla Regulates Sympathetic and Cardiac Vagal Outflows.

The ventrolateral medulla contains presympathetic and vagal preganglionic neurons that control vasomotor and cardiac vagal tone, respectively. G protein-coupled receptors influence the activity of these neurons. Gα s activates adenylyl cyclases, which drive cyclic adenosine monophosphate (cAMP)-dependent targets: protein kinase A (PKA), the exchange protein activated by cAMP (EPAC), and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. The aim was to determine the cardiovascular effects of activating and inhibiting these targets at presympathetic and cardiac vagal preganglionic neurons. Urethane-anesthetized rats were instrumented to measure splanchnic sympathetic nerve activity (sSNA), arterial pressure (AP), heart rate (HR), as well as baroreceptor and somatosympathetic reflex function, or were spinally transected and instrumented to measure HR, AP, and cardiac baroreflex function. All drugs were injected bilaterally. In the rostral ventrolateral medulla (RVLM), Sp-cAMPs and 8-Br-cAMP, which activate PKA, as well as 8-pCPT, which activates EPAC, increased sSNA, AP, and HR. Sp-cAMPs also facilitated the reflexes tested. Sp-cAMPs also increased cardiac vagal drive and facilitated cardiac baroreflex sensitivity. Blockade of PKA, using Rp-cAMPs or H-89 in the RVLM, increased sSNA, AP, and HR and increased HR when cardiac vagal preganglionic neurons were targeted. Brefeldin A, which inhibits EPAC, and ZD7288, which inhibits HCN channels, each alone had no effect. Cumulative, sequential blockade of all three inhibitors resulted in sympathoinhibition. The major findings indicate that Gα s-linked receptors in the ventral medulla can be recruited to drive both sympathetic and parasympathetic outflows and that tonically active PKA-dependent signaling contributes to the maintenance of both sympathetic vasomotor and cardiac vagal tone.

Autonomic activity and biomarker behavior in supine position and after passive postural stress in different orthostatic intolerance syndromes

Introduction and objectivesOrthostatic intolerance (OI) syndromes are a confusing topic and determining a specific diagnosis to achieve optimal treatment can be troublesome. We sought to assess biomarker, hemodynamic and autonomic variables in OI patients (autonomic dysfunction [AD], postural orthostatic tachycardia syndrome [POTS] and neurally mediated syncope [NMS]) and healthy controls during supine and head-up tilt position in order to achieve a better diagnosis. ResultsIn response to head-up tilt, patients with AD presented a marked decrease in systolic blood pressure (SBP) (p=0.002), and a blunted increase in heart rate (HR) (p=0.04). Baroreceptor gain was almost absent in supine position and did not change in response to tilt. Patients with POTS had lower values of atrial natriuretic peptide (p=0.03) but similar neurohormonal biomarkers and hemodynamic and baroreceptor function in supine position compared to healthy subjects. However, in response to head-up tilting greater reductions in stroke volume (p=0.008) and baroreceptor gain (p=0.002) and greater rises in HR (p=0.001), total peripheral resistance (p=0.008), low frequency component of SBP variability (LF-SBP) (p=0.003) and plasma noradrenaline (p=0.03) were observed. Patients with NCS had similar biomarkers and autonomic indices to healthy subjects in supine position, but a larger decrease in baroreceptor gain (p=0.007) and a greater rise in LF-SBP (p=0.004) and plasma adrenaline (p=0.003) response to head-up tilting. ConclusionAlthough different OI syndromes share similar symptoms, including blurred vision, syncope and dizziness particularly during orthostatism, they differ markedly regarding biochemical, autonomic and hemodynamic parameters. Assessment of these differences may be helpful for better diagnosis and management.

Autonomic activity and biomarker behavior in supine position and after passive postural stress in different orthostatic intolerance syndromes

Introduction and objectivesOrthostatic intolerance (OI) syndromes are a confusing topic and determining a specific diagnosis to achieve optimal treatment can be troublesome. We sought to assess biomarker, hemodynamic and autonomic variables in OI patients (autonomic dysfunction [AD], postural orthostatic tachycardia syndrome [POTS] and neurally mediated syncope [NMS]) and healthy controls during supine and head-up tilt position in order to achieve a better diagnosis. ResultsIn response to head-up tilt, patients with AD presented a marked decrease in systolic blood pressure (SBP) (p=0.002), and a blunted increase in heart rate (HR) (p=0.04). Baroreceptor gain was almost absent in supine position and did not change in response to tilt. Patients with POTS had lower values of atrial natriuretic peptide (p=0.03) but similar neurohormonal biomarkers and hemodynamic and baroreceptor function in supine position compared to healthy subjects. However, in response to head-up tilting greater reductions in stroke volume (p=0.008) and baroreceptor gain (p=0.002) and greater rises in HR (p=0.001), total peripheral resistance (p=0.008), low frequency component of SBP variability (LF-SBP) (p=0.003) and plasma noradrenaline (p=0.03) were observed. Patients with NCS had similar biomarkers and autonomic indices to healthy subjects in supine position, but a larger decrease in baroreceptor gain (p=0.007) and a greater rise in LF-SBP (p=0.004) and plasma adrenaline (p=0.003) response to head-up tilting. ConclusionAlthough different OI syndromes share similar symptoms, including blurred vision, syncope and dizziness particularly during orthostatism, they differ markedly regarding biochemical, autonomic and hemodynamic parameters. Assessment of these differences may be helpful for better diagnosis and management.

Effect of Superficial Cervical Plexus Block on Baroreceptor Sensitivity in Patients Undergoing Carotid Endarterectomy

Regional anesthesia for patients undergoing carotid endarterectomy is associated with improved intraoperative hemodynamic stability compared with general anesthesia. The authors hypothesized that the reported advantages might be related to attenuated ipsilateral baroreflex control of blood pressure, caused by chemical denervation of the carotid bulb baroreceptor nerve fibers. A prospective cohort study. Single-center university hospital. The study included 46 patients undergoing carotid endarterectomy using superficial cervical block. A noninvasive computational periprocedural measurement of baroreceptor sensitivity was performed in all patients. Two groups were formed, depending on the patients' subjective response to surgical stimulation regarding the necessity of additional intraoperative local anesthesia (LA) administration on the carotid bulb. Group A (block alone) included 23 patients who required no additional anesthesia, and group B (block + LA) consisted of 23 patients who required additional anesthesia. Baroreceptor sensitivity showed no significant change after application of the block in both groups (group A: median [IQR], 5.19 [3.07-8.54] v 4.96 [3.1-9.07]; p = 0.20) (group B: median [IQR], 4.47 [3.36-8.09] v 4.53 [3.29-8.01]; p = 0.55). There was a significant decrease in baroreceptor sensitivity in group B after intraoperative LA administration (median [IQR], 4.53 [3.29-8.01] v 3.31 [2.26-7.31]; p = 0.04). Standard superficial cervical plexus block did not impair local baroreceptor function, and, therefore, it was not related to improved cerebral perfusion in awake patients undergoing carotid endarterectomy. However, direct infiltration of the carotid bulb was associated with the expected attenuation of baroreflex sensitivity.

Altered ENaC is Associated With Aortic Baroreceptor Dysfunction in Chronic Heart Failure.

Abnormal baroreceptor function contributes to attenuated arterial baroreflex sensitivity in chronic heart failure (CHF). As a mechanosensor in mammalian nonepithelium, the epithelial sodium channel (ENaC) is an amiloride-sensitive and voltage-independent ion channel. The ENaC is thought to be a component of baroreceptor mechanosensitive ion channels in aortic baroreceptor cell bodies and nerve terminals. In this study, therefore, we measured the expression and activation of the ENaC in nodose neuronal cell bodies and aortic baroreceptor nerve terminals in sham and CHF rats. CHF was induced by surgical ligation of left coronary artery. The development of CHF was confirmed by hemodynamic and morphological characteristics. The aortic baroreceptor sensitivity was blunted in anesthetized CHF rats, compared with that in sham rats. The data from immunostaining and western blot analysis showed that the protein of β- and γ-ENaC subunits was expressed in nodose neuronal cell bodies and aortic baroreceptor nerve terminals, whereas the protein of α-ENaC subunit was undetectable. CHF reduced protein expression of β- and γ-ENaC subunits in nodose neuronal cell bodies and aortic baroreceptor nerve terminals. Additionally, the data recorded by the whole cell patch-clamp technique demonstrated that ENaC currents in aortic baroreceptor neurons were lower in CHF rats than that in sham rats. These results suggest that reduced protein expression of the ENaC decreases the ENaC activation, which could be involved in attenuation of the aortic baroreceptor sensitivity in the CHF state. Baroreceptors should be a potential therapeutic target for reducing mortality in CHF.

Calcium/calmodulin-dependent kinase II inhibition in smooth muscle reduces angiotensin II-induced hypertension by controlling aortic remodeling and baroreceptor function.

BackgroundMultifunctional calcium/calmodulin-dependent kinase II (CaMKII) is activated by angiotensin II (Ang II) in cultured vascular smooth muscle cells (VSMCs), but its function in experimental hypertension has not been explored. The aim of this study was to determine the impact of CaMKII inhibition selectively in VSMCs on Ang II hypertension.Methods and ResultsTransgenic expression of a CaMKII peptide inhibitor in VSMCs (TG SM-CaMKIIN model) reduced the blood pressure response to chronic Ang II infusion. The aortic depressor nerve activity was reset in hypertensive versus normotensive wild-type animals but not in TG SM-CaMKIIN mice, suggesting that changes in baroreceptor activity account for the blood pressure difference between genotypes. Accordingly, aortic pulse wave velocity, a measure of arterial wall stiffness and a determinant of baroreceptor activity, increased in hypertensive versus normotensive wild-type animals but did not change in TG SM-CaMKIIN mice. Moreover, examination of blood pressure and heart rate under ganglionic blockade revealed that VSMC CaMKII inhibition abolished the augmented efferent sympathetic outflow and renal and splanchnic nerve activity in Ang II hypertension. Consequently, we hypothesized that VSMC CaMKII controls baroreceptor activity by modifying arterial wall remodeling in Ang II hypertension. Gene expression analysis in aortas from normotensive and Ang II–infused mice revealed that TG SM-CaMKIIN aortas were protected from Ang II–induced upregulation of genes that control extracellular matrix production, including collagen. VSMC CaMKII inhibition also strongly altered the expression of muscle contractile genes under Ang II.ConclusionsCaMKII in VSMCs regulates blood pressure under Ang II hypertension by controlling structural gene expression, wall stiffness, and baroreceptor activity.

Cardiovascular Autonomic Dysfunction in Chronic Kidney Disease: a Comprehensive Review

Cardiovascular autonomic dysfunction is a major complication of chronic kidney disease (CKD), likely contributing to the high incidence of cardiovascular mortality in this patient population. In addition to adrenergic overdrive in affected individuals, clinical and experimental evidence now strongly indicates the presence of impaired reflex control of both sympathetic and parasympathetic outflow to the heart and vasculature. Although the principal underlying mechanisms are not completely understood, potential involvements of altered baroreceptor, cardiopulmonary, and chemoreceptor reflex function, along with factors including but not limited to increased renin-angiotensin-aldosterone system activity, activation of the renal afferents and cardiovascular structural remodeling have been suggested. This review therefore analyzes potential mechanisms underpinning autonomic imbalance in CKD, covers results accumulated thus far on cardiovascular autonomic function studies in clinical and experimental renal failure, discusses the role of current interventional and therapeutic strategies in ameliorating autonomic deficits associated with chronic renal dysfunction, and identifies gaps in our knowledge of neural mechanisms driving cardiovascular disease in CKD.

PP.LB01.19

Objective: Patients with atherosclerotic carotid disease usually do not present clinically overt signs of orthostatic dysregulation. In the present study we aimed at investigating if the presence of atherosclerotic plaque in the carotid sinus may alter baroreceptor function and thus heart rate variability (HRV) time-domain indices of autonomic tone and baroreflex sensitivity. Design and method: This was a cross-sectional study. We evaluated ECG R-R intervals in asymptomatic patients with carotid disease with an intima-media thickening (IMT) more than 0.8 mm. The atherosclerotic artery IMT was determined by B-mode and duplex ultrasonography. Baroreflex sensitivity and autonomic tone were determined through time-domain measures of HRV. Results: Of all time-domain measures of HRV investigated, we identified significant negative linear correlations between the common carotid artery IMT and time-domain HRV indexes reflecting baroreflex and autonomic tone: SDNN (standard deviation of R-R intervals), Spearman's r = −0.57, 95% CI: −0.78 to −0.25, P = 0.001; HRV triangular index (number of all R-R intervals / maximum number), Spearman's r = −0.62, 95% CI: −0.80 to −0.33, P = 0.0002; TINN (triangular interpolation of R-R intervals), Spearman's r = −0.59, 95% CI: −0.78 to −0.28, P = 0.0006. Similar strong negative correlations were found for subclavian IMT. Conclusions: Our data indicate that the SDNN, triangular index and TINN HRV biomarkers may be early predictors of atherosclerotic carotid and subclavian in subjects at risk and may be an indicator for ultrasound evaluation.

Chronic electroacupuncture of the ST36 point improves baroreflex function and haemodynamic parameters in heart failure rats.

Electroacupuncture (EA) has been used to treat many diseases, including heart failure (HF). This study aimed to evaluate the effects of chronic stimulation in the ST36 acupuncture point on haemodynamic parameters and baroreflex function in rats with HF. Cardiovascular parameters assessed were heart rate (HR), blood pressure (BP), and the reflex cardiovascular response of HR triggered by stimulation of baroreceptors in animals with HF subsequent to acute myocardial infarction (AMI). Male Wistar rats were divided into three groups: Sham Control - animals without HF and without EA; HF Control group - animals with HF and without EA; and HF EA group - animals with HF that received the EA protocol. Six weeks after surgical induction of AMI, the EA protocol (8 weeks, 5 times a week) was performed. The protocol was applied with EA at the ST36 point, frequency of 2 Hz, pulse of 0.3 ms and intensity of 1-3 mA for 30 min. Haemodynamic parameters and baroreceptor function were assessed. There was no difference between groups in the variables HR, systolic blood pressure (SBP) and diastolic blood pressure (DBP), which were evaluated with awake animals (p>0.05). There was an increase in the mean arterial pressure (MAP) in the HF EA group compared to the HF Control group (p<0.05). The maximum gain of the baroreflex heart rate response (Gain) was higher in the HF EA group than the HF Control and Sham Control groups. Chronic EA in the ST36 point increased the MAP and baroreflex sensitivity in rats with HF.

Abstracts From the 36th Annual Scientific Meeting of the HBPRCA

### CONTRIBUTION OF THE AREA POSTREMA TO THE INCREASED CARDIAC SYMPATHETIC NERVE ACTIVITY IN OVINE HEART FAILURE Abukar Y, Ramchandra R, May CN The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia Background : Heart failure (HF) is associated with an increase in cardiac sympathetic nerve activity (CSNA), which is directly linked to mortality in HF patients. The mechanisms responsible for the elevated CSNA remain unclear. Previous studies indicate that the area postrema (AP), a circumventricular organ in the brainstem, plays a role in the control of sympathetic nerve activity. We hypothesized that the elevated CSNA in HF is mediated by the AP and lesioning this region would reduce the increased CSNA in sheep with HF. Aims : To determine the effect of sham lesion or lesion of the AP on CSNA and hemodynamics in conscious sheep with HF. Methods : Studies were conducted in 2 groups of sheep with pacing-induced HF: sham (n=6) and AP lesion (n=6) sheep. Mean arterial blood pressure (MAP), heart rate (HR) and CSNA were recorded simultaneously in conscious sheep at least 4 days after surgery. Results : Heart failure was associated with a significant decrease in ejection fraction (from 74±2 % to 38±1 %; P<0.001), which was similar in both groups. There was a significant reduction in CSNA burst incidence in the AP lesion group compared with the sham group (45±10 and 89±3 bursts/100 heartbeats, respectively; P<0.01). Conclusions : In sheep with HF, the group with lesion of the AP had a significantly lower CSNA compared with the sham group. These data suggest that the AP plays a role in setting the detrimental high levels of CSNA in HF. ### G PROTEIN-COUPLED ESTROGEN RECEPTOR SIGNALING IMPROVES STROKE OUTCOME IN FEMALE MICE Broughton BRS, Jansen GL, Sobey CG Department of Pharmacology, Monash University, Clayton, Victoria, Australia Background: Estrogen has been assumed to provide neuroprotection following stroke entirely via classical estrogen receptors. Interestingly, there is recent evidence that activation of a novel G …

Faster Lower Limb Blood Pooling Is Associated with Reduced LBNP‐Tolerance in Women Prone to Vasovagal Syncope

Objective We recently presented slower lower limb venous blood pooling in healthy women with reduced orthostatic tolerance. Venous distension rate affects the prevailing sympathetic response, and people prone to syncope seem to have altered cardiovascular response to orthostatic stress. The aim was to study lower limb blood pooling and its effects on tolerance to lower body negative pressure (LBNP) in women prone to vasovagal syncope (VVS). Methods: Graded LBNP to presyncope was used to determine LBNP tolerance index (LTI) in 13 young women with VVS and 15 matched controls. During LBNP the blood pooling rate was evaluated with volumetric technique. Cardiovascular responses were also monitored. Results: Within the control group, a faster rate of blood pooling was associated with increased LTI (P < 0.05), and in addition correlated to a smaller LBNP-induced decline in stroke volume (P < 0.05) and pulse pressure (P < 0.05). In contrast, within the VVS group a faster rate of blood pooling was associated with decreased LTI (P < 0.01), and with a greater decline in stroke volume (P < 0.05). Conclusions In accordance with the previous study, a faster rate of lower limb blood pooling was associated with increased orthostatic tolerance in women with no history of syncope. Interestingly, the opposite pattern was found in women prone to vasovagal syncope, indicating essential differences in blood pressure regulation. One plausible mechanism could be altered baroreceptor function and/or different concomitant sympathetic response during hypovolemic stimulus in women prone to vasovagal syncope.

The Probiotic Kefir Improves Cardiovascular Function in Spontaneously Hypertensive Rats

In the present study, we evaluated the effects of the probiotic kefir on the cardiovascular function in spontaneously hypertensive rats (SHR). SHR were chronically administered with oral 0.3 mL/100 g b.w. of kefir (SHR‐k) or vehicle (SHR‐v) for 60 days and compared with Wistar rats (WR). In comparison with NWR, SHR‐v exhibited higher mean arterial pressure, which was significantly attenuated in SHR‐k (108±2, 194±5 and 142±8 mmHg, respectively, p&lt;0.01). Similarly effects were observed on angiotensin converting enzyme activity (91±7, 119±9 and 78±6%, respectively, p&lt;0.01). The evaluation of the baroreceptor function showed that the attenuated gain (bpm/mmHg) of the baroreflex observed in SHR‐v (3.85±0.03) when compared with WR (6.3±0.05) was significantly improved in SHR‐k (5.8±0.04). Evalulation of vascular endothelium function showed that aortic rings from SHR‐v had impaired maximum relaxing responses (%) and sensitivity (‐log M) to acetylcholine (48±1.7 and 6.7±0.09) when compared with WR (78±1.4 and 8.0±0.07), which were significantly improved in SHR‐k (59±1.3 and 7.4±0.07). These data show evidence of beneficial effects of the probiotic kefir on high blood pressure and endothelial dysfunction in the this genetic model of hypertension. The current study expands the many health benefits have been attributed to kefir. Ongoing experiments are being directed to clear the mechanisms of the beneficial effects of this probiotic on the cardiovascular function. Financial support from: FAPES and CNPq.

Baroreceptor dysfunction, diabetes mellitus, and takotsubo syndrome: An intricate triangle needing exploration

In the intriguing contribution by Ali et al. [1], published ahead of print, in the December 30, 2014 issue of the Journal, the authors propose that an impaired baroreceptor function (IBF) leads to an excessive sympathetic activity which could cause Takotsubo syndrome (TTS), via an unopposed inotropic and chronotropic stimulation which in turn results in the development of excess wall tension within certain regions in the left ventricle. In this conceptualization, TTS emerges via a regional shutdown of contractile activity (a form of protective myocardial stunning), engendered by the cardiomyocytes, which have perceived the above described excess wall tension, as a demand:supply mismatch, as the authors have proposed previously [2,3].

Effects of anesthetics on the renal sympathetic response to anaphylactic hypotension in rats.

The autonomic nervous system plays an important role in rat anaphylactic hypotension. It is well known that sympathetic nerve activity and cardiovascular function are affected by anesthetics. However, the effects of different types of anesthesia on the efferent renal sympathetic nerve activity (RSNA) during anaphylactic hypotension remain unknown. Therefore, we determined the renal sympathetic responses to anaphylactic hypotension in anesthetized and conscious rats and the roles of baroreceptors in these responses. Sprague-Dawley rats were randomly allocated to anesthetic groups that were given pentobarbital, urethane, or ketamine-xylazine and to a conscious group. The rats were sensitized using subcutaneously injected ovalbumin. The systemic arterial pressure (SAP), RSNA and heart rate (HR) were measured. The effects of sinoaortic baroreceptor denervation on RSNA during anaphylaxis were determined in pentobarbital-anesthetized and conscious rats. In all of the sensitized rats, the RSNA increased and SAP decreased after antigen injection. At the early phase within 35 min of the antigen injection, the antigen-induced sympathoexcitation in the conscious rats was significantly greater than that in the anesthetized rats. Anaphylactic hypotension was attenuated in the conscious rats compared to the anesthetized rats. The anesthetic-induced suppression of SAP and RSNA was greater in the order ketamine-xylazine >urethane = pentobarbital. Indeed, in the rats treated with ketamine-xylazine, RSNA did not increase until 40 min, and SAP remained at low levels after the antigen injection. The baroreceptor reflex, as evaluated by increases in RSNA and HR in response to the decrease in SAP induced by sodium nitroprusside (SNP), was suppressed in the anesthetized rats compared with the conscious rats. Consistent with this finding, baroreceptor denervation attenuated the excitatory responses of RSNA to anaphylaxis in the conscious rats but not in the pentobarbital-anesthetized rats. RSNA was increased markedly in conscious rats during anaphylactic hypotension. Anesthetics attenuated this antigen-induced renal sympathoexcitation through the suppression of baroreceptor function.

Abstract 19204: Symptoms of Depression and Posttraumatic Stress Disorder are Associated with Differential Autonomic Influences to Standing

Introduction: Depression and posttraumatic stress disorder (PTSD) are associated with impaired baroreflex sensitivity, a risk factor for sudden death. Unlike depression, PTSD is associated with hyperarousal. We hypothesized that, in patients with CAD, depressive and PTSD symptoms associate with different autonomic responses to standing (baroreflex response). Methods: We examined 178 patients with CAD for autonomic dysfunction with the ANSAR test (ANX 3.0, ANSAR Inc. Philadelphia, PA) in which heart rate variability was measured in both sitting (5 minutes) and standing (5 minutes) positions. Sympathetic (SNS) and parasympathetic (PNS) nervous system activity was measured using continuous wavelet transform and log-transformed. PTSD symptoms were assessed using the PTSD checklist scale (PCL), and depressive symptoms were assessed using the Beck Depression Inventory-II (BDI). Both BDI and PCL were examined in multivariate models simultaneously, adjusting for CAD risk factors, beta blockers, and antidepressants. Results: The mean (SD) age, BDI, and PCL scores were 62.4 (9.1), 7.2 (7.6), and 26.2 (10.2), respectively. For the group as a whole, the mean baseline SNS and PNS tones were -0.49 and -0.60 log beats per minute squared (log BPM 2 ). In multivariable models, PCL score associated with higher baseline SNS tone (β=0.03, p=0.046). With standing, PCL score associated with decrease in the levels of SNS tone (β=-0.02, p=0.02) vs. sitting, and BDI associated with an increased PNS tone (β=0.03, p=0.03) vs. sitting. In both cases, these responses are the opposite of the expected autonomic response to standing, which is an increase in SNS tone and decrease in PNS tone vs. sitting. Conclusion: Depressive and PTSD symptoms have opposite autonomic pathologies in CAD patients. While PTSD symptoms are associated with higher SNS tone at baseline, they are also associated with lower sympathetic activation with standing. Depressive symptoms, on the other hand, are associated with reduced vagal withdrawal with standing. This suggests that both depressive and PTSD symptoms are associated with an abnormal baroreceptor function, but through different autonomic pathways.

Cardiovascular Autonomic Function in Patients with OSA

Objectives: Prospectively investigate the cardiovascular autonomic function in patients with obstructive sleep apnea (OSA) and examine the relationship with OSA severity, since impaired cardiovascular autonomic response is independently associated with cardio- and cerebro-vascular disease. Methods: Ninety-one subjects with symptoms of sleep-disordered breathing who underwent full-night polysomnography were recruited. Standard autonomic parameters which include heart rate response to deep breathing, Valsalva ratio, baroreflex sensitivity (BRS), and heart rate variability were obtained for further analysis and correlated to severity of OSA. Results: Seventy-three patients with OSA (apnea/hypopnea index, AHI ≥5/h) and 18 simple snore patients (AHI &lt;5) as normal control were compared in this study. BRS was the only parameter with significant difference among the 2 groups (3.6 ± 1.2 in simple snore and 2.8 ± 1.4 in OSA patients, P = .03). Further association analysis revealed significant correlation between BRS and AHI. Conclusions: This study shows OSA patients have blunted baroreceptor function compared to patients without OSA. Baroreceptor dysfunction may contribute to an increase in cardiovascular morbidity in OSA patients.

Role of autonomic reflex arcs in cardiovascular responses to air pollution exposure.

The body responds to environmental stressors by triggering autonomic reflexes in the pulmonary receptors, baroreceptors, and chemoreceptors to maintain homeostasis. Numerous studies have shown that exposure to various gases and airborne particles can alter the functional outcome of these reflexes, particularly with respect to the cardiovascular system. Modulation of autonomic neural input to the heart and vasculature following direct activation of sensory nerves in the respiratory system, elicitation of oxidative stress and inflammation, or through other mechanisms is one of the primary ways that exposure to air pollution affects normal cardiovascular function. Any homeostatic process that utilizes the autonomic nervous system to regulate organ function might be affected. Thus, air pollution and other inhaled environmental irritants have the potential to alter both local airway function and baro- and chemoreflex responses, which modulate autonomic control of blood pressure and detect concentrations of key gases in the body. While each of these reflex pathways causes distinct responses, the systems are heavily integrated and communicate through overlapping regions of the brainstem to cause global effects. This short review summarizes the function of major pulmonary sensory receptors, baroreceptors, and carotid body chemoreceptors and discusses the impacts of air pollution exposure on these systems.

Field stimulation of the carotid baroreceptor complex does not compromise baroreceptor function in spontaneously hypertensive rats.

Field stimulation of the carotid baroreceptors has been successfully used to induce a long-term reduction in blood pressure. However, baroreceptor stimulation may interfere with or compromise the beneficial short-term blood pressure regulation function of the baroreceptors. This study aims to quantify the baroreceptor function before and during acute, unilateral field stimulation of the carotid baroreceptors. Spontaneously Hypertensive Rats (n=7) were anaesthetised and instrumented to measure heart rate and mean arterial pressure (MAP), aortic pulse wave velocity (a surrogate measure of arterial stiffness), abdominal aortic flow and renal artery flow. A custom made field stimulation device was fitted to the left common carotid artery. Baroreceptor function was measured by quantifying heart rate response to MAP change induced by bolus injection of phenylephrine. Field stimulation of the baroreceptors reduced heart rate by 20 bpm (p=0.003) with MAP reduction of 18 mmHg (p=0.008). Maximal barorecep-tor gain without stimulation was -1.20±0.41 bpm/mmHg and during stimulation -1.41±0.52 bpm/mmHg (p=0.59). The MAP at which maximal gain occurred also did not change (152±11, 160±9 mmHg respectively, p=0.22). This study indicates that unilateral field stimulation of the carotid baroreceptor complex, while causing a sustained reduction of arterial pressure, does not alter acute baroreceptor function peak gain.

10 Autonomic Responses to Head Up Tilt in Patients with Syncope: The Influence of Ageing

Introduction Neurally mediated syncope is a common disorder but there remain large gaps in our understanding of its pathophysiology. Several groups have studied the role of the autonomic nervous system (ANS), baroreceptor sensitivity (BRS) and baroreceptor effectiveness (BEI) in syncope but have offered conflicting results. We hypothesised that patients who experience symptoms during head-up tilt testing (HUT) would have abnormal ANS and baroreceptor responses and that these changes may alter with advancing with age. Methods We analysed HUT data from tests performed at Ealing Hospital between 2004–2012. These were clinically indicated HUT for individuals who experienced either syncope or pre-syncope. The Italian protocol was used during HUT. Beat-to-beat heart rate and non-invasive plethysmographic blood pressure monitoring was employed throughout, using the Task Force Monitor® (CN Systems, Graz, Austria). The device calculates short-term frequency domain heart rate variability (HRV) using an autoregressive algorithm, BRS using the sequence method and cardiac output using impedance cardiography. Results HUT assessments in 298 patients were reviewed, there was no syncope in 187, 31 experienced syncope without GTN, 78 experienced syncope with GTN and 3 had carotid sinus syndrome (CSS). There was a bimodal age distribution for these HUT patients (Figure 1). CSS was found only in those > 60 years. There were differences across tertiles of age with respect to haemodynamics and ANS, BRS and BEI responses (Table 1). However, there were no differences, across tertiles of age, in the proportions of negative HUT, those positive without GTN and those positive with GTN (χ 2 , p = 0.445). For the different stages of HUT, there were no significant differences in HRV and BRS between individuals who experienced syncope (with or without GTN) and those that did not. Conclusions Autonomic nervous system variability and baroreceptor function at rest decline with age but this does not seem to influence the nature of syncope on HUT.