Baroreceptor Function Research Articles

Caffeine, gravity, and baroreceptor function: the integration of diet and cardiovascular control.

We describe a simple, cost-effective experiment to demonstrate cardiovascular integration of heart rate and blood pressure to accommodate the environmental and dietary factors of gravity and caffeine. Specific learning objectives associated with this include understanding the effects of posture on blood pressure and heart rate, coupled with the role of caffeine in modifying this response. Inclusion of ECG measurements, coupled with heart rate variability analysis, added a demonstration of the contribution made by the autonomic nervous system under these conditions. We clearly demonstrate that the cardiac work, estimated as rate-pressure product, necessary to undertake the transition from supine to standing, is fixed for a given group of subjects. However, the individual contribution of heart rate and systolic pressure to the cardiac workload is subject to the external factors of gravity and caffeine. Such an activity also demonstrates additional benefits, including unstructured teaching opportunities to augment classroom learning associated with integrative physiology and also the discussion of ethical issues with regard to human experimentation.

Modified Sequence Method to Assess Baroreflex Sensitivity in Rats.

Baroreceptors respond to fluctuations in blood pressure (BP) by modifying physiology in order to maintain a homeostatic set point. Baroreflex sensitivity (BRS) is used to quantify baroreceptor function and is a useful metric for tracking cardiovascular disease state and treatment effects. Pathological conditions such as hypertension (HTN) alter baroreflex function and reduce BRS. Traditionally, the sequence method is used to measure BRS, in which the linear slope of concomitant changes in BP and RR intervals are assessed. However, in rats, a high respiratory rate reduces the reliability of the sequence method. Here, we present a modified sequence method that captures BRS at lower frequencies and decreases the variability of the BRS estimate. This method was demonstrated using ECG and BP data from two groups of HTN rats: Sham rats and rats treated with vagus nerve stimulation. The modified sequence method resulted in lower BRS estimates than the traditional sequence technique when applied to the same data sets. Additionally, the modified sequence method resulted in lower BRS estimate variability.

Carotid Body Ablation: a New Target to Address Central Autonomic Dysfunction.

An abnormal heightened carotid body (CB) chemoreflex, which produces autonomic dysfunction and sympathetic overactivation, is the common hallmark of obstructive sleep apnea (OSA), resistant hypertension, systolic heart failure (HF), and cardiometabolic diseases. Accordingly, it has been proposed that the elimination of the CB chemosensory input to the brainstem may reduce the autonomic and cardiorespiratory alterations in sympathetic-associated diseases in humans. A growing body of evidence obtained in preclinical animal models support that an enhanced CB discharge produces sympathetic hyperactivity, baroreflex sensitivity and heart rate variability impairment, breathing instability, hypertension, and insulin resistance. The elimination CB chemosensory input reduces the sympathetic hyperactivity, the elevated arterial blood pressure in OSA and hypertensive models, abolishes breathing instability and improves animal survival in HF models, and restores insulin tolerance in metabolic models. These results highlight the role played by the enhanced CB drive in the progression of sympathetic-related diseases and support the proposal that the surgical ablation of the CB is useful to restore the autonomic balance and normal cardiorespiratory function in humans. Accordingly, the CB ablation has been used in pilot human studies as a therapeutic treatment for resistant hypertension and HF-induced sympathetic hyperactivity. In this review, I will discuss the supporting evidence for a crucial contribution of the CB in the central autonomic dysfunction and the pros and cons of the CB ablation as a therapy to revert autonomic overactivation. The CB ablation could be a useful method to reverse the enhanced chemoreflex in HF and severe hypertension, but caution is required before extensive use of bilateral CB ablation, which abolished ventilatory responses to hypoxia and may impair baroreceptor function.

A method for assessment of the dynamic response of the arterial baroreflex.

The baroreflex is a key mechanism in cardiovascular regulation, and alterations in baroreceptor function are seen in many diseases, including heart failure, obesity and hypertension. We propose a new method for analysing baroreceptor function from continuous blood pressure (BP) and heart rate (HR) in both health and disease. Forty-eight-hour data series of BP and HR were collected with telemetry. Sprague Dawley rats on standard chow (n = 11) served as controls, while rats on a high-fat, high-fructose (HFHC) diet (n = 6) constituted the obese-hypertensive model. A third group of rats underwent autonomic blockade (n = 6). An autoregressive-moving-average with exogenous inputs (ARMAX) model was applied to the data and compared with the α-coefficient. Autonomic blockade caused a significant reduction in the strength of the baroreflex as estimated by ARMAX [ARMAX- baroreflex sensitivity (BRS)] -0.03 ± 0.01 vs. -0.19 ± 0.04 bpm heartbeat-1) . Both methods showed a ~50% reduction in BRS in the obese-hypertensive group compared with control (body weight 531 ± 27 vs. 458 ± 19 g, P < 0.05; mean arterial pressure 119 ± 3 vs. 102 ± 1 mmHg, P < 0.05; ARMAX-BRS -0.08 ± 0.01 vs. -0.15 ± 0.01 bpm heartbeat-1 , P < 0.05; α-coefficient BRS 0.51 ± 0.07 vs. 0.89 ± 0.07 ms mmHg-1 , P < 0.05). The ARMAX method additionally showed the open-loop gain of the baroreflex to be reduced by ~50% in the obese-hypertensive group (-2.3 ± 0.3 vs. -4.1 ± 0.3 bpm, P < 0.05), while the rate constant was similar between groups. The ARMAX model represents an efficient method for estimating several aspects of the baroreflex. The open-loop gain of the baroreflex was attenuated in obese-hypertensive rats compared with control, while the time response was similar. The algorithm can be applied to other species including humans.

Differential effects of renal denervation on arterial baroreceptor function in Goldblatt hypertension model.

Sympathetic vasomotor activity is significantly increased in renovascular hypertension. Renal denervation (DnX) has emerged as a novel therapy for resistant hypertension to drug therapy. However, the underlying mechanisms regarding the reduction in blood pressure (BP) after DnX remain unclear. Thus, the aim of this study was to evaluate the effects of DnX of a clipped kidney on the baseline and baroreceptor reflex control of post-ganglionic sympathetic activity to the contralateral kidney (rSNA) and lumbar (lSNA) nerves in Goldblatt hypertensive rats (2K1C). Renal denervation of an ischaemic kidney (DxX - all visible bundles of nerves were dissected - 10% phenol) was performed 5weeks after clipping (gap width: 0.2mm). Ten days after DnX, BP was significantly reduced (16%) in the 2K1C compared with the undenervated 2K1C (p<0.05). DnX significantly reduced basal rSNA (control group (CT): 110±8, n=14; 2K1C: 150±8, n=12; 2K1C DnX: 89±7, spikes per second (spikes/s); p<0.05, n=8) and lSNA (CT: 137±8, n=8; 2K1C: 202±7, n=11; 2K1C DnX: 131±7, spikes/s; p<0.05, n=8) only in 2K1C rats. DnX significantly improved the arterial baroreceptor sensitivity of rSNA (CT: -2.3±0.2, n=11; 2K1C: -0.7±0.1, n=8; 2K1C DnX: -1.5±0.2, spikes/s/mmHg; p<0.05, n=5) and heart rate for tachycardic response (CT: -3.9±0.5, n=7; 2K1C: -1.9±0.1, n=8; 2K1C DnX: -3.3±0.4, bpm/mmHg; p<0.05, n=8), but not for lSNA in 2K1C rats. The results show that DnX normalized baseline sympathetic vasomotor activity to the lumbar and renal nerves, followed by a differential improvement in the arterial baroreceptor sensitivity. Whether the baroreceptor function sensitivity improvement induced by DnX is a cause or a consequence of BP reduction remains to be determined.

The antioxidant effects of green tea reduces blood pressure and sympathoexcitation in an experimental model of hypertension.

Oxidative stress is a key mediator in the maintenance of sympathoexcitation and hypertension in human and experimental models. Green tea is widely known to be potent antioxidant. We aimed to evaluate the effects of green tea in a model of hypertension. Hypertension was induced by the nitric oxide synthase inhibitor [N-nitro-L-arginine-methyl-ester (L-NAME); 20 mg/kg per day, orally, for 2 weeks] in male Wistar rats. After the first week of L-NAME treatment, animals received green tea ad libitum for 1 week. At the end of the treatment period, blood pressure, heart rate, baroreflex sensitivity, renal sympathetic nerve activity, and vascular and systemic oxidative stress were assessed. L-NAME-treated animals exhibited an increase in blood pressure (165 ± 2 mmHg) compared with control rats (103 ± 1 mmHg) and green tea treatment reduced hypertension (119 ± 1 mmHg). Hypertensive animals showed a higher renal sympathetic nerve activity (161 ± 12 spikes/s) than the control group (97 ± 2 spikes/s), and green tea also decreased this parameter in the hypertensive treated group (125 ± 5 spikes/s). Arterial baroreceptor function and vascular and systemic oxidative stress were improved in hypertensive rats after green tea treatment. Taken together, short-term green tea treatment improved cardiovascular function in a hypertension model characterized by sympathoexcitation, which may be because of its antioxidant properties.

A Case of Accelerated Hypertension Complicated by Acute Coronary Syndrome and Bezold Jarisch Reflex

A 73-year-old woman presented with acute coronary syndrome on a background of worsening symptoms of left heart failure and accelerated hypertension. Patient was severely hypertensive with clinical findings suggestive of acute pulmonary congestion on presentation. Whilst being stabilised with medical therapy, patient developed multiple episodes of prolonged asystole (Fig. 1) with ongoing severe uncontrolled hypertension requiring haemodynamic support with temporary wire. Improved hypertension control over the next 24 hours stabilised the patient without recurrence of bradyarrhythmia. Secondary causes of severe hypertension were excluded and culprit ramus artery was stented. Bezold Jarisch reflex is a triad of bradycardia, asystole and hypotension which has been implicated in various cardiac conditions [[1]Mark A.L. The Bezold Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart.J Am Coll Cardiol. 1983; 1: 90-102Crossref PubMed Scopus (568) Google Scholar]. This case demonstrates accelerated hypertension complicated by acute coronary syndrome and acute pulmonary odema with multiple episodes of Bezold Jarisch Reflex mediated bradycardia and asystole. Asystolic episodes resulted from increased vagal stimulation due to stretching of mechanoreceptors in ventricular myocytes during accelerated hypertensive episode [[2]Julius S. Esler M. Increased central blood volume: a possible pathophysiological factor in mild low-renin esse ntial hypertension.Clin Sci Mol Med Suppl. 1976; 3: 207s-210sPubMed Google Scholar]. Decongestive therapy and optimisation of hypertension control resulted in complete resolution of bradyarrhythmia. Recognition of association of BJR with accelerated hypertension is important because treatment of hypertension restores the baroreceptor function without requiring permanent pacing.

Hypertension and Frailty Syndrome in Old Age: Current Perspectives.

Hypertension is both a health problem and a financial one globally. It affects nearly 30 % of the general population. Elderly people, aged ≥65 years, are a special group of hypertensive patients. In this group, the overall prevalence of the disease reaches 60 %, rising to 70 % in those aged ≥80 years. In the elderly population, isolated systolic hypertension is quite common. High systolic blood pressure is associated with an increased risk of cardiovascular disease, cerebrovascular disease, peripheral artery disease, cognitive impairment and kidney disease. Considering the physiological changes resulting from ageing alongside multiple comorbidities, treatment of hypertension in elderly patients poses a significant challenge to treatment teams. Progressive disability with regard to the activities of daily life, more frequent hospitalisations and low quality of life are often seen in elderly patients. There is discussion in the literature regarding frailty syndrome associated with old age. Frailty is understood to involve decreased resistance to stressors, depleted adaptive and physiological reserves of a number of organs, endocrine dysregulation and immune dysfunction. The primary dilemma concerning frailty is whether it should only be defined on the basis of physical factors, or whether psychological and social factors should also be included. Proper nutrition and motor rehabilitation should be prioritised in care for frail patients. The risk of orthostatic hypotension is a significant issue in elderly patients. It results from an autonomic nervous system dysfunction and involves maladjustment of the cardiovascular system to sudden changes in the position of the body. Other significant issues in elderly patients include polypharmacy, increased risk of falls and cognitive impairment. Chronic diseases, including hypertension, deteriorate baroreceptor function and result in irreversible changes in cerebral and coronary circulation. Concurrent frailty or other components of geriatric syndrome in elderly patients are associated with a worse perception of health, an increased number of comorbidities and social isolation of the patient. It may also interfere with treatment adherence. Identifying causes of non-adherence to pharmaceutical treatment is a key factor in planning therapeutic interventions aimed at increasing control, preventing complications, and improving long-term outcomes and any adverse effects of treatment. Diagnosis of frailty and awareness of the associated difficulties in adhering to treatment may allow targeting of those elderly patients who have a poorer prognosis or may be at risk of complications from untreated or undertreated hypertension, and for the planning of interventions to improve hypertension control.

Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome.

BackgroundThe potential benefit of SGLT2 inhibitors in metabolic syndrome is with prediabetic stage unclear. This work was undertaken to investigate the non-glycemic effect of empagliflozin on metabolic syndrome rats with prediabetes.MethodsSHR/NDmcr-cp(+/+) rats (SHRcp), a model of metabolic syndrome with prediabetes, were given empagliflozin for 10 weeks to examine the effects on urinary sodium and water balance, visceral and subcutaneous adipocyte, and cardiac injury. Further, the effect of empagliflozin on blood pressure and autonomic nervous system was continuously investigated by using radiotelemetry system.ResultsEmpagliflozin significantly reduced urinary sodium and water balance of SHRcp only within 1 week of the treatment, but later than 1 week did not alter them throughout the treatment. Empagliflozin significantly reduced body weight of SHRcp, which was mainly attributed to the significant reduction of subcutaneous fat mass. Empagliflozin significantly reduced the size of visceral adipocytes and increased the number of smaller size of adipocytes, which was associated with the attenuation of oxidative stress. Empagliflozin ameliorated cardiac hypertrophy and fibrosis of SHRcp, in association with the attenuation of cardiac oxidative stress and inflammation. However, empagliflozin did not significantly change blood pressure, heart rate, sympathetic activity, or baroreceptor function, as evidenced by radiotelemetry analysis.ConclusionsOur present work provided the evidence that SGLT2 inhibition reduced visceral adipocytes hypertrophy and ameliorated cardiac injury in prediabetic metabolic syndrome rat, independently of diuretic effect or blood pressure lowering effect. Thus, SGLT2 inhibition seems to be a promising therapeutic strategy for prediabetic metabolic syndrome.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0473-7) contains supplementary material, which is available to authorized users.

PP.LB02.15] RENAL DENERVATION NORMALIZES SYMPATHETIC VASOMOTOR ACTIVITY AND PRODUCES DIFFERENTIAL EFFECTS ON THE ARTERIAL BARORECEPTOR FUNCTION IN THE GOLDBLATT RENOVASCULAR HYPERTENSION

Objective: Sympathetic nerve activity is increased in renovascular hypertension. Renal denervation has shown promise in the treatment of patients with resistant hypertension to drug therapy, although the mechanisms underlying reduction in blood pressure remains uncertain. The aim of this study was to evaluate the effects of unilateral renal denervation (H+DnX) on efferent post-ganglionic sympathetic nerve activity to renal (rSNA) and lumbar (lSNA) sympathetic nerves in Goldblatt hypertensive rats (2K1C). Design and method: The baroreceptor sensitivity to rSNA, lSNA, heart rate (HR) and the cardiovascular autonomic function (by power spectral density analysis) were evaluated ten days after renal denervation. Denervation of clipped kidney (DnX – all visible bundles nerves were dissected – 10% phenol) was performed 5 weeks after clipping (gap width 0.2 mm). The rSNA and barorreceptor reflex control to rSNA was performed in the innervated contralateral kidney. Results: Ten days after DnX, blood pressure (BP) was significantly reduced (16%) in the 2K1C rats compared to 2K1C undenervated (H). DnX normalized rSNA (CT: 110 ± 8, n = 14; 2K1C:150 ± 8, n = 12; 2K1C DnX:89 ± 7, pps n = 8) and lSNA (CT: 137 ± 8, n = 8; 2K1C: 202 ± 7, n = 11; 2K1C DnX:131 ± 7, pps n = 8) in the 2K1C rats. DnX significantly improved the baroreceptor function for rSNA (CT: −2.3 ± 0.2, n = 11; 2K1C: −0.7 ± 0.1, n = 8; 2K1C DnX: −1.5 ± 0.2, pps/mmHg n = 5) and tachycardic response (CT: −3.9 ± 0.5, n = 7; 2K1C: −1.9 ± 0.1, n = 8; 2K1C DnX: −3.3 ± 0.4, bpm/mmHg n = 8), but not for lSNA in 2K1C rats. Furthermore, DnX significantly increased the high frequency (HF) component (CT: 1.4 ± 1, n = 10; 2K1C: 3.4 ± 2 n = 9; 2K1C DnX: 7.6 ± 3, ms2 n = 9) but not the very low frequency (VLF) and low frequency (LF) components (VLF = CT: 2.7 ± 1, n = 10; 2K1C: 13 ± 7, n = 9; 2K1C DnX: 9 ± 5, ms2 n = 8 / LF = CT: 2 ± 0.6, n = 9; 2K1C: 5 ± 3, n = 11; 2K1C DnX: 6 ± 4, ms2 n = 9) which remained elevated in the 2K1C rats. Conclusions: The results show that renal denervation normalized sympathetic vasomotor activity and increased the HF component of spectral analysis accompanied by a non uniform improvement in the arterial baroreceptor function. Whether the baroreceptor function sensitivity improvement induced by DnX is a cause or a consequence of BP reduction remains to be determined. Supported by FAPESP and CAPES.

PP.39.10] EFFECT OF IMAGE MEDICINE TREATMENT ON COGNITIVE FUNCTION AND AUTONOMIC NERVOUS SYSTEM BALANCE IN ARTERIAL HYPERTENSION

Objective: To evaluate the effectiveness of Image medicine treatment on cognitive function and autonomic nervous system balance in arterial hypertension patients.. Design and method: Investigation was approved by Ethics Committee. Each patient siagned Inform Consent Form. Strong Inclusion and exclusion criteria were elaborated, The changes in antyhypertnesive therapy during nonmedical treatment were not allowed. Patients were tested by physician and Image medicine specialist before treatment. 13 from 17 Arterial hypertension patients (men, aged from 35–57 yrs) were included in investigation. Arterial blood pressure, heart rate, autonomic nervous system function (heart rate variability, baroreceptor function) using Physiograph Task Force Monitor (Austria) and orthostatic tilt - table test, Cognitive Function using Vienna test system (Schuffried, Austria), questionnaires - SF - 36, Satisfaction with life scale and Subjective Happiness scale parameters were analyzed before and after 1.5 months treatment. Results: The obtained data showed that after 1.5 months nonmedical therapy heart rate, diastolic and systolic blood pressure have statistical tendency for decreasing. The function of arterial baroreceptor reflex statistically increased (P = 0.006) and sympathetic - parasympathetic balance (heart rate variability) during rest and orthisatatic test improved. The cognitive function has tendency to increase, mainly reaction time and characteristics of attention. Subjective Happiness scale parameters increase from 4.1 to 5.6. There are no dynamics in Satisfaction with life. Conclusions: The Imagine Medicine treatment lasting 1.5 months improve such cardiovascular parameters as arterial blood pressure, heart rate, heart rate variability and arterial baroreceptor function. The function of autonomic nervous system also improve. The cognitive function parameters, mainly reaction time, attention and Subjective Happiness increased. Is is concluded that non medical treatment possibilities would be added to standard therapy for better treatment results. The next steps are follow up study and enlargement of respondents group. The study in Control group also will be performed.

PP.38.09] EFFECTS OF MILD DYNAMIC EXERCISE ON CIRCULATORY AND AUTONOMIC FUNCTION IN HEALTHY VOLUNTEERS

Objective: Valuable insights into BP regulation have arisen from the study of neurocirculatory responses to exercise. However most studies have focused exclusively on evaluation of responses to maximal/submaximal exercise with concomitant profound increase in muscle metabolic demand. We studied the effects of mild exercise in healthy volunteers to obviate the confounding effects of large metabolic changes. Design and method: 8 healthy volunteers undertook very mild dynamic exercise (< 3 METs) of 1 minute duration. Non-invasive arterial BP was monitored in all 8 subjects. In 5 subjects the arterial BP recording was used to derive haemodynamic variables (PulseCO®, LiDCO plc, London), including cardiac output (CO), mean arterial pressure (MAP), systemic vascular resistance (SVR) and heart rate. Autonomic nervous system investigation was undertaken in 7 subjects with high resolution monitoring of arterial pressure and electrocardiography to derive indices of sympathetic and parasympathetic tone (NeuroScope®, Medifit Instruments Ltd, London). Results: CO increased from an average resting value of 4.8 l min-1 to 6.2 l min-1 during exercise (a 30.4% increase, p = 0.003) and settled to 4.8 l min-1 afterwards. The reciprocal of SVR, conductance (100/SVR) was used to determine the role of the periphery on CO in positive terms (the other driver for the increase in CO being MAP change). The average increase in MAP and conductance was 4.4% (p = ns) and 23.8% (p = 0.01) respectively.Cardiac sensitivity to baroreceptor function (CSB) fell from an average of 5.4 ± 1.2 SEM to 2.9 ± 1.2 SEM (p < 0.05) and cardiac vagal tone (CVT) fell from an average of 6.8 ± 1.3 SEM on a linear vagal scale to 4.1 ± 1.3 SEM, (p < 0.05). Following exercise rebound occurred with both to values above baseline. Conclusions: The main change driving the increase in CO was an increase in conductance rather than change in MAP. This is in contrast to dynamic cardiovascular exercise at higher workloads where MAP increases immediately and progressively with workload. Withdrawal of vagal tone at such mild exercise intensity is a new finding and is consistent with gradual heart rate increase as exercise intensity increases from the lowest levels.

Abstract PR047

Background & Objectives: Intraoperative hemodynamic instability (IHI) is a well-known complication of carotid endarterectomy (CEA). It is a common perioperative finding depends on the timing and type of surgery, iatrogenic manipulation of the baroreceptors and is influenced by the anesthetic management. Carotid artery stenting (CAS) is an alternative to CEA and may be associated with hypotension and bradycardia due to predominantly parasympathetic activity during placement of the stent. This study aims to compare the incidence of IHI between CAS and CEA. Materials & Methods: The medical records of 80 patients underwent CAS and 101 patients underwent CEA under cervical plexus block during a 10 month period at our institution, were retrospectively reviewed. The Vascular Study Group of New England Cardiac Risk Index (VSG-CRI) was used to classify CAS and CEA patients into 3 groups: low (I), medium (II) and high risk group (III), separately. IHI was defined as an increase/decrease in systolic and diastolic blood pressure or heart rate for ≥20% from basal value, for 2 minutes. In accordance to VSG-CRI, the incidence of IHI in low, medium and high risk group was compared among patients underwent CAS and CEA. Results: In line with VSG-CRI, patients underwent CEA were divided into three groups: group I consisted of 59 patients (56.2%), group II of 25 (23.8%) and group III of 21 (20%). Also, patients underwent CAS were divided into three groups, group I: 40 patients (50 %), group II: 30 (37.5%) and group III: 10 (12.5%). In low risk group, the incidence of bradycardia was significantly higher in the patients underwent CAS compared to the CEA patients (p=0.01). There was significantly higher incidence of IHI in the patients underwent CEA compared to the CAS patients in medium risk group (II) (p=0.03). In this group, diastolic blood pressure values immediately after cervical block application, were significantly higher in the patients underwent CEA compared to the CAS patients (p=0.009). Conclusion: According to VSG-CRI, in our study IHI and bradycardia were occured more often after CEA in medium and low risk group, respectively. This findings could suggest that the alteration of baroreceptor function is related more to the underlying carotid atherosclerotic disease that affects baroreceptor, than to the stenting procedure.

Autonomic outcome is better after endarterectomy than after stenting in patients with asymptomatic carotid stenosis

Carotid endarterectomy and stenting have comparable efficacy in stroke prevention in asymptomatic carotid stenosis. In patients with carotid stenosis, cardiac events have a more than threefold higher incidence than cerebrovascular events. Autonomic dysfunction predicts cardiovascular morbidity and mortality, and carotid stenosis interferes with baroreceptor and chemoreceptor function. We assessed the effect of elective carotid revascularization (endarterectomy vs stenting) on autonomic function as a major prognostic factor of cardiovascular health. In 42 patients with ≥70% asymptomatic extracranial carotid stenosis, autonomic function was determined by analysis of heart rate variability (total band power [TP], high frequency band power [HF], low-frequency band power [LF], very low frequency band power [VLF]), baroreflex sensitivity (αHF, αLF), respiratory chemoreflex sensitivity (central apnea-hypopnea index), and cardiac chemoreflex sensitivity (hyperoxic TP, HF, LF, and VLF ratios) before and 30days after revascularization. Patients with endarterectomy were older than patients with stenting (69± 7 vs 62± 7years; P ≤ .008) but did not differ in gender distribution and preintervention autonomic function. Compared with stenting, postintervention heart rate variability was higher (ln TP, 6.7 [95% confidence interval (CI), 6.3-7.0] vs 6.1 [95% CI, 5.8-6.5; P ≤ .009]; ln HF, 4.5 [95% CI, 4.1-5.0] vs 4.0 [95% CI, 3.4-4.5; P ≤ .05]; ln VLF, 6.0 [95% CI, 5.7-6.4] vs 5.5 [95% CI, 5.2-5.9; P≤.02]); respiratory chemoreflex sensitivity (central apnea-hypopnea index, 5.5 [95% CI, 2.8-8.2] vs 10.0 [95% CI, 6.9-13.1; P ≤. 01]) and cardiac chemoreflex sensitivity (TP ratio, 1.2 [95% CI, 1.1-1.3] vs 1.0 [95% CI, 0.9-1.0; P ≤ .0001]; HF ratio, 1.4 [95% CI, 1.2-1.5] vs 0.9 [95% CI, 0.8-1.1; P ≤ .001]; LF ratio, 1.5 [95% CI, 1.3-1.6] vs 1.0 [95% CI, 0.8-1.1; P ≤ .0001]; VLF ratio, 1.2 [95% CI, 1.1-1.3) vs 1.0 [95% CI, 0.9-1.1; P ≤ .002]) were lower after endarterectomy. Postintervention baroreflex sensitivity did not differ after endarterectomy and stenting. Autonomic function was better after endarterectomy than after stenting. Better autonomic function after endarterectomy was based on restoration of chemoreceptor but not baroreceptor function and may improve cardiovascular long-term outcome.

Case Report: Carotid Sinus Hypersensitivity During Internal Jugular Venous Cannulation

Carotid sinus hypersensitivity is common in elderly patients. Baroreceptor function generally decreases with age but some people experience hypersensitive carotid baroreflexes. In such individuals, even mild stimulation to the neck results in profound bradycardia and hypotension. In this case, CSH was elicited during internal jugular venous cannulation which is a common procedure in cardiac surgery. Knowledge about CSH can help us to take appropriate precautions in perioperative period and manage cardiac instability arising from this reflex.

Acute hypertensive response in ischemic stroke is associated with increased aortic stiffness

Background and aimsAcute hypertensive response (AHR) affects more than 60% of patients with ischemic stroke and is associated with poor outcomes. We hypothesized that its development is related to arterial stiffening. “The gold standard” estimate of arterial stiffness is carotid-femoral pulse wave velocity (CF-PWV). We compared CF-PWV and indirect indices of arterial stiffness (central augmentation index (cAIxHR), central systolic (cSBP) and pulse (cPP) pressures) between acute ischemic stroke patients who developed AHR and those who were normotensive in the early phase of stroke. MethodsAHR was assessed through hourly BP measurements within 24 h from admission using an oscillometric device. The stiffness was assessed using applanation tonometry with a SphygmoCor® device (Atcor, Sydney, Australia) 7 ± 2 days after stroke. ResultsAmong 102 patients with acute ischemic stroke, 73(71.5%) met AHR criteria. In an univariate analysis, CF-PWV, cAIxHR, cSBP and cPP were higher in those who developed AHR (10.9 vs. 8.3 m/s, p < 0.001; 30.8 vs. 23.9%, p = 0.004; 138.2 vs. 117.2 mmHg, p < 0.001; 54.6 vs. 44 mmHg, p = 0.005, respectively). In a multivariate logistic regression analysis, CF-PWV was independently associated with AHR after adjustment for age and peripheral mean blood pressure (pMBP) (p = 0.04), for age, pMBP and diabetes mellitus (DM) (p = 0.045), and age, pMBP, DM and hypertension (p = 0.047). ConclusionThis study revealed for the first time that AHR in ischemic stroke is associated with elevated aortic stiffness independently of other clinical factors including age and hypertension preceding stroke. A potential pathophysiological mechanism responsible for this relationship includes impaired baroreceptor function in stiff arteries resulting in impaired BP autoregulation.

Creating adequate pulsatility with a continuous flow left ventricular assist device: just do it!

Continuous flow left ventricular assist devices (LVADs) have revolutionized the treatment of advanced heart failure; however, as experience with these devices has grown, a number of unanticipated adverse events have emerged. In this study, we review the current literature associating a lack of pulsatility with these events. It is now evident that continuous flow LVAD physiology reflects a spectrum of 'low pulsatile' rather than a truly 'nonpulsatile' state. Thus, the detrimental consequences of nonpulsatile flow noted in early experimental setups may or may not occur in humans supported with continuous flow LVADs. Such studies have demonstrated not only alterations in vascular function and structure during continuous flow LVAD support, but also a clear association of the degree of alterations in vascular, baroreceptor, and sympathetic nervous system function with the degree of actual pulsatility. In addition, a number of clinical events have been linked to continuous flow LVAD physiology, including a decreased extent of ventricular unloading possibly impairing myocardial recovery, hemolysis and device thrombosis, development of aortic insufficiency, and mucosal bleeding. Many of the adverse effects of the current continuous flow LVADs are associated with low pulsatile flow. An evolved understanding of pulsatility as a continuous rather than a binary variable may allow us to incorporate appropriate degrees of pulsatility into the next generation pumps and mitigate these effects.

Autonomic Responses to Orthostasis after Acetylcholinesterase Inhibition in Tetraplegia

PURPOSE: We have demonstrated that acetylcholinesterase inhibition (AcHi: pyridostigmine bromide: PB) improves orthostatic blood pressure (BP) responses to head-up tilt (HUT) compared to no drug (ND) in some individuals with tetraplegia and theorize that difference between subjects with an orthostatic BP response to PB (responders [R]) and those without a BP response (non-responders [nR]) may relate to the autonomic completeness of injury. Although we cannot directly asses the degree of autonomic cardiovascular impairment, we determined differences in the autonomic response to HUT using heart rate (HR) variability (HFV) and BP variability (BPV) after administration of PB (60 mg) compared to ND in subjects with tetraplegia. METHODS: Mixed factor ANOVA was used to determine main and interaction effects for high frequency HRV (HF: vagal) and low frequency BPV (LFsbp: sympathetic) responses to HUT (0°, 15°, 25°, 35°) following PB and ND administration in the R and nR. Beat-to-beat HR and BP were assessed using a 3-lead ECG and finger photoplethysmography, respectively; data were collected at 500 Hz for 5-minutes at each angle of HUT. RESULTS: Eleven individuals with SCI participated; however, one subject was unable to tolerate the HUT maneuver during ND therefore, results are presented in 10 subjects (age: 38±10 years; duration of injury: 13±10 years; level: C4-6; AIS: A, B, C). Five individuals were R and 5 were nR (+6.9±5.5 vs. -7.1±8.1 mmHg, respectively; p=0.012); demographics did not differ between the groups. Supine HR was lower in R compared to nR (48±3 vs. 57±8 bpm, respectively; p=0.049); supine BP did not differ. Although supine HF did not differ, supine LFsbp was increased in R compared to the nR (4.11±0.12 vs.3.82±0.24 ln, respectively; p=0.041). The group (R, nR) by condition (PB, ND) by HUT interaction effect was significant for HF (3.639; p=0.044), but not for LFsbp. CONCLUSION: These data suggest that tetraplegic individuals with increased resting sympathetic nervous system activity (LFsbp) respond to AcHi with an increased BP and vagal response to HUT, indicative of improved orthostatic baroreceptor function.

ARMAX‐based Method Extends Knowledge of the Baroreflex

IntroductionThe arterial baroreceptor‐heart rate reflex (baroreflex) is a key mechanism in regulating the cardiovascular system, and alterations in baroreceptor function are seen in many disease states, including heart failure, obesity and hypertension. Recent studies have identified impairment of the baroreflex early in the clinical course of hypertension. We propose a new and simple method for analyzing these alterations in baroreceptor function. The method is validated to describe dynamic relationships in causal systems with feedback, and in addition to the traditional estimate of baroreflex sensitivity (BRS) it adds information on two new valuable components of the reflex. Firstly, the average time for the baroreflex to reach its maximal effect on heart rate (HR) following a change in blood pressure (BP), and secondly, the average maximal change in HR produced by the baroreflex. This study aims to validate the method against a traditional method of estimating BRS in both healthy animals and in a verified model of diet‐induced obesity and hypertension.Methods48‐hour data series of continuous BP and HR recordings were collected with telemetry and used for analysis. 16‐weeks‐old SD rats on standard chow (n=11) served as healthy controls, while a similar group of rats on a high‐fat, high‐fructose (HFHC) diet from 4 weeks of age (n=6) constituted the obese hypertension model. An Autoregressive–moving‐average model with exogenous inputs (ARMAX)‐based algorithm was applied to the data series and compared with the α‐coefficient.ResultsThe ARMAX‐based method matched the traditional method, and interestingly when comparing the obese hypertension group with controls (body weight 531±27 vs. 458±19 g, p&lt;0.05; mean arterial pressure 119±3 vs. 102±1 mmHg, p&lt;0.05) the same degree of attenuation in BRS of ~50 % could be observed in the obese hypertensive group compared with controls with both methods (ARMAX: −0.08±0.01 vs. −0.15±0.01 Δbpm/heartbeat, p&lt;0.05; α‐coefficient: 0.51±0.07 vs. 0.89±0.07 ms/mmHg, p&lt;0.05). The ARMAX‐based method additionally demonstrated the maximal change in HR following a BP change to be reduced by ~50 % in the obese hypertensive group compared with controls (1.3±0.2 vs. −2.6±0.2 Δbpm, p&lt;0.05), while the time until the maximal change in HR was reached was similar between groups.ConclusionThe ARMAX‐based method confirms traditional methods and presents an unbiased method of characterizing HR changes in response to changes in BP. The method further contributes to our understanding of the reflex by providing information on time to maximal change in HR as well as the degree of maximal change in HR. The presented algorithm can potentially be applied to other species including humans.Support or Funding InformationPregraduate Research Scholarship from The Danish Council for Independent Research, Grant from Fru Ruth König Petersens Foundation, Helge Peetz and Verner Peetz and Hustrus Scholarship.

Electrical stimulation of the aortic depressor nerve in conscious rats overcomes the attenuation of the baroreflex in chronic heart failure.

Chronic heart failure (CHF) is characterized by autonomic dysfunction combined with baroreflex attenuation. The hypotensive and bradycardic responses produced by electrical stimulation of the aortic depressor nerve (ADN) were examined in conscious CHF and control male Wistar rats (12-13 wk old). Furthermore, the role of parasympathetic and sympathetic nervous system in mediating the cardiovascular responses to baroreflex activation was evaluated by selective β1-adrenergic and muscarinic receptor antagonists. CHF was induced by myocardial infarction. After 6 wk, the subjects were implanted with electrodes for ADN stimulation. Twenty-four hours later, electrical stimulation of the ADN was applied for 20 s using five different frequencies (5, 15, 30, 60, and 90 Hz), while the arterial pressure was recorded by a catheter implanted into the femoral artery. Electrical stimulation of the ADN elicited progressive and similar hypotensive and bradycardic responses in control (n = 12) and CHF (n = 11) rats, while the hypotensive response was not affected by methylatropine. Nevertheless, the reflex bradycardia was attenuated by methylatropine in control, but not in CHF rats. Atenolol did not affect the hypotensive or bradycardic response in either group. The ADN function was examined under anesthesia through electroneurographic recordings. The arterial pressure-ADN activity relationship was attenuated in CHF rats. In conclusion, despite the attenuation of baroreceptor function in CHF rats, the electrical stimulation of the ADN elicited a stimulus-dependent hypotension and bradycardia of similar magnitude as observed in control rats. Therefore, electrical activation of the aortic baroreflex overcomes both the attenuation of parasympathetic function and the sympathetic overdrive.