RESUMEN

Preclinical models indicate that amiloride (AMD) reduces baroreflex sensitivity and perturbs homeostatic blood pressure (BP) regulation. However, it remains unclear whether these findings translate to humans. This study investigated whether oral administration of AMD reduces spontaneous cardiac and sympathetic baroreflex sensitivity and perturbs BP regulation in healthy young humans. Heart rate (HR; electrocardiography), beat-to-beat BP (photoplethysmography), and muscle sympathetic activity (MSNA, microneurography) were continuously measured in 10 young subjects (4 females) during rest across two randomized experimental visits: 1) after 3 h of oral administration of placebo (PLA, 10 mg of methylcellulose within a gelatin capsule) and 2) after 3 h of oral administration of AMD (10 mg). Visits were separated for at least 48 h. We calculated the standard deviation and other indices of BP variability. Spontaneous cardiac baroreflex was assessed via the sequence technique and cardiac autonomic modulation through time- and frequency-domain HR variability. The sensitivity (gain) of the sympathetic baroreflex was determined via weighted linear regression analysis between MSNA and diastolic BP. AMD did not affect HR, BP, and MSNA compared with PLA. Indexes of cardiac autonomic modulation (time- and frequency-domain HR variability) and BP variability were also unchanged after AMD ingestion. Likewise, AMD did not modify the gain of both spontaneous cardiac and sympathetic arterial baroreflex. A single oral dose of AMD does not affect spontaneous arterial baroreflex sensitivity and BP variability in healthy young adults.NEW & NOTEWORTHY Preclinical models indicate that amiloride (AMD), a nonselective antagonist of the acid-sensing ion channels (ASICs), impairs baroreflex sensitivity and perturbs blood pressure regulation. We translated these findings into humans, investigating the impact of acute oral ingestion of AMD on blood pressure variability and spontaneous cardiac and sympathetic baroreflex sensitivity in healthy young humans. In contrast to preclinical evidence, AMD does not impair spontaneous arterial baroreflex sensitivity and blood pressure variability in healthy young adults.

Asunto(s)

Amilorida , Barorreflejo , Presión Sanguínea , Frecuencia Cardíaca , Humanos , Barorreflejo/efectos de los fármacos , Barorreflejo/fisiología , Amilorida/farmacología , Amilorida/administración & dosificación , Masculino , Femenino , Adulto , Frecuencia Cardíaca/efectos de los fármacos , Adulto Joven , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Administración Oral , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/fisiología , Bloqueadores del Canal de Sodio Epitelial/farmacología , Bloqueadores del Canal de Sodio Epitelial/administración & dosificación

RESUMEN

PURPOSE: Hypertension is one of the major causes of cardiovascular morbidity and mortality in the USA and disproportionately affects Black women. Endothelial-derived nitric oxide (eNO) substantially regulates blood pressure in humans, and impaired NO-mediated vasodilation has been reported in the Black population. Previous studies using an NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA) did not fully determine the NO contribution to blood pressure because of baroreflex buffering. Therefore, in the present study we used trimethaphan, a ganglionic blocker, to inhibit baroreflex buffering and study NO modulation of blood pressure in Black women during L-NMMA infusion. METHODS: L-NMMA at doses of 250 µg/kg per minute was infused in combination with trimethaphan at doses of 4 mg/min to eliminate baroreflex mechanisms. Heart rate (HR) was obtained with continuous electrocardiogram monitoring, and continuous blood pressure was measured with the volume clamp method. The increase in systolic blood pressure (SBP) during both infusions was used to estimate the contribution of NO to blood pressure. RESULTS: Ten Black (age range 30-50 years, body mass index [BMI] 30-45 kg/m2), and nine White women (age range 30-50 years, body mass index 30-45 kg/m2) were enrolled in this study. During autonomic blockade, there was no difference in the decrease in SBP between Black and White women (- 20 ± 16.45 vs. - 24 ± 15.49 mm Hg, respectively; P = 0.659). When autonomic blockade was combined with L-NMMA, Black women had a significant increase in SBP compared to White women (54 ± 13.62 vs. 39 ± 09.64 mm Hg, respectively; P = 0.022, respectively). CONCLUSION: Autonomic blood pressure regulation was similar between Black and White women. However, NO contribution to blood pressure was significantly greater in Black women compared to White women. REGISTRATION: ClinicalTrials.gov: NCT01122407.

Asunto(s)

Barorreflejo , Presión Sanguínea , Óxido Nítrico , Obesidad , omega-N-Metilarginina , Humanos , Femenino , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Adulto , Obesidad/fisiopatología , Barorreflejo/efectos de los fármacos , Barorreflejo/fisiología , omega-N-Metilarginina/farmacología , Negro o Afroamericano , Trimetafan/farmacología , Persona de Mediana Edad , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Bloqueadores Ganglionares/farmacología , Sistema Nervioso Autónomo/efectos de los fármacos , Sistema Nervioso Autónomo/fisiología

RESUMEN

Permanent residence at high-altitude and chronic mountain sickness (CMS) may alter the cerebrovascular homeostasis and orthostatic responses. Healthy male participants living at sea-level (LL; n = 15), 3800 m (HL3800m; n = 13) and 5100 m (HL5100m; n = 17), respectively, and CMS highlanders living at 5100 m (n = 31) were recruited. Middle cerebral artery mean blood flow velocity (MCAv), cerebral oxygen delivery (CDO2), mean blood pressure (MAP), heart rate variability and spontaneuous cardiac baroreflex sensitivity (cBRS) were assessed while sitting, initial 30 s and after 3 min of standing. Cerebral autoregulation index (ARI) was estimated (ΔMCAv%baseline)/ΔMAP%baseline) in response to the orthostatic challenge. Altitude and CMS were associated with hypoxemia and elevated hemoglobin concentration. While sitting, MCAv and LFpower negatively correlated with altitude but were not affected by CMS. CDO2 remained preserved. BRS was comparable across all altitudes, but lower with CMS. Within initial 30 s of standing, altitude and CMS correlated with a lesser ΔMAP while ARI remained unaffected. After 3 min standing, MCAv, CDO2 and cBRS remained preserved across altitudes. The LF/HF ratio increased in HL5100m compared to LL and HL3800m from sitting to standing. In contrary, CMS showed blunted autonomic nervous activation in responses to standing. Despite altitude- and CMS-associated hypoxemia, erythrocytosis and impaired blood pressure regulation (CMS only), cerebral homeostasis remained overall preserved.

Asunto(s)

Mal de Altura , Altitud , Barorreflejo , Presión Sanguínea , Circulación Cerebrovascular , Frecuencia Cardíaca , Homeostasis , Humanos , Masculino , Mal de Altura/fisiopatología , Adulto , Presión Sanguínea/fisiología , Frecuencia Cardíaca/fisiología , Barorreflejo/fisiología , Circulación Cerebrovascular/fisiología , Persona de Mediana Edad , Velocidad del Flujo Sanguíneo , Arteria Cerebral Media/fisiopatología , Hipoxia/fisiopatología

RESUMEN

We hypothesized that sympathetic hyperactivity and parasympathetic insuficiency in spontaneously hypertensive rats (SHR) underlie their exaggerated cardiovascular response to acute stress and impaired adaptation to repeated restraint stress exposure compared to Wistar-Kyoto rats (WKY). Cardiovascular responses to single (120 min) or repeated (daily 120 min for 1 week) restraint were measured by radiotelemetry and autonomic balance was evaluated by power spectral analysis of systolic blood pressure variability (SBPV) and heart rate variability (HRV). Baroreflex sensitivity (BRS) was measured by the pharmacological Oxford technique. Stress-induced pressor response and vascular sympathetic activity (low-frequency component of SBPV) were enhanced in SHR subjected to single restraint compared to WKY, whereas stress-induced tachycardia was similar in both strains. SHR exhibited attenuated cardiac parasympathetic activity (high-frequency component of HRV) and blunted BRS compared to WKY. Repeated restraint did not affect the stress-induced increase in blood pressure. However, cardiovascular response during the post-stress recovery period of the 7th restraint was reduced in both strains. The repeatedly restrained SHR showed lower basal heart rate during the dark (active) phase and slightly decreased basal blood pressure during the light phase compared to stress-naive SHR. SHR subjected to repeated restraint also exhibited attenuated stress-induced tachycardia, augmented cardiac parasympathetic activity, attenuated vascular sympathetic activity and improved BRS during the last seventh restraint compared to single-stressed SHR. Thus, SHR exhibited enhanced cardiovascular and sympathetic responsiveness to novel stressor exposure (single restraint) compared to WKY. Unexpectedly, the adaptation of cardiovascular and autonomic responses to repeated restraint was more effective in SHR.

Asunto(s)

Adaptación Fisiológica , Sistema Nervioso Autónomo , Barorreflejo , Presión Sanguínea , Frecuencia Cardíaca , Hipertensión , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Restricción Física , Animales , Presión Sanguínea/fisiología , Frecuencia Cardíaca/fisiología , Sistema Nervioso Autónomo/fisiopatología , Masculino , Ratas , Adaptación Fisiológica/fisiología , Barorreflejo/fisiología , Hipertensión/fisiopatología , Estrés Psicológico/fisiopatología

RESUMEN

Chronic hypertensive pregnancy (CHP) is a growing health issue with unknown etiology. Vasopressin (VP), a nonapeptide synthesized in paraventricular (PVN) and supraoptic nucleus (SON), is a well-known neuroendocrine and autonomic modulator of the cardiovascular system, related to hypertension development. We quantified gene expression of VP and its receptors, V1aR and V1bR, within the PVN and SON in CHP and normal pregnancy, and assessed levels of secreted plasma VP. Also, we evaluated autonomic cardiovascular adaptations to CHP using spectral indices of blood pressure (BPV) and heart rate (HRV) short-term variability, and spontaneous baroreflex sensitivity (BRS). Experiments were performed in female spontaneously hypertensive rats (SHRs) and in normotensive Wistar rats (WRs). Animals were equipped with a radiotelemetry probe for continuous hemodynamic recordings before and during pregnancy. BPV, HRV and BRS were assessed using spectral analysis and the sequence method, respectively. Plasma VP was determined by ELISA whilst VP, V1aR, and V1bR gene expression was analyzed by real-time-quantitative PCR (RT-qPCR). The results show that non-pregnant SHRs exhibit greater VP, V1aR, and V1bR gene expression in both PVN and SON respectively, compared to Wistar dams. Pregnancy decreased VP gene expression in the SON of SHRs but increased it in the PVN and SON of WRs. Pregnant SHRs exhibited a marked drop in plasma VP concentration associated with BP normalization. This triggered marked tachycardia, heart rate variability increase, and BRS increase in pregnant SHRs. It follows that regardless of BP normalization in late pregnancy, SHRs exhibit cardiovascular vulnerability and compensate by recruiting vagal mechanisms. Pregnant SHR dams have reduced expression of VP in SON associated with increased V1bR expression, lower plasma VP, normal BP during late pregnancy and marked signs of enhanced sympathetic cardiac stimulation (increased HR and LFHR variability) and recruitment of vagal mechanisms (enhancement of BRS and HFHR variability).

Asunto(s)

Barorreflejo , Presión Sanguínea , Frecuencia Cardíaca , Vasopresinas , Animales , Femenino , Embarazo , Ratas , Sistema Nervioso Autónomo/fisiopatología , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Frecuencia Cardíaca/fisiología , Hipertensión Inducida en el Embarazo/fisiopatología , Núcleo Hipotalámico Paraventricular/metabolismo , Núcleo Hipotalámico Paraventricular/fisiopatología , Ratas Endogámicas SHR , Ratas Wistar , Receptores de Vasopresinas/metabolismo , Núcleo Supraóptico/metabolismo , Vasopresinas/sangre , Vasopresinas/metabolismo

Asunto(s)

Barorreflejo , Hipertensión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antihipertensivos/uso terapéutico , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Terapia por Estimulación Eléctrica/métodos , Hipertensión/fisiopatología , Hipertensión/terapia , Proyectos Piloto , Resultado del Tratamiento

RESUMEN

BACKGROUND: The accurate selection of patients likely to respond to renal denervation (RDN) is crucial for optimizing treatment outcomes in patients with hypertension. This systematic review was designed to evaluate patient-specific factors predicting the RDN response. METHODS AND RESULTS: We focused on individuals with hypertension who underwent RDN. Patients were categorized based on their baseline characteristics. The primary outcome was blood pressure (BP) reduction after RDN. Both randomized controlled trials and nonrandomized studies were included. We assessed the risk of bias using corresponding tools and further employed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the overall quality of evidence. A total of 50 studies were ultimately included in this systematic review, among which 17 studies were for meta-analysis. Higher baseline heart rate and lower pulse wave velocity were shown to be associated with significant antihypertensive efficacy of RDN on 24-hour systolic BP reduction (weighted mean difference, -4.05 [95% CI, -7.33 to -0.77]; weighted mean difference, -7.20 [95% CI, -9.79 to -4.62], respectively). In addition, based on qualitative analysis, higher baseline BP, orthostatic hypertension, impaired baroreflex sensitivity, and several biomarkers are also reported to be associated with significant BP reduction after RDN. CONCLUSIONS: In patients with hypertension treated with the RDN, higher heart rate, and lower pulse wave velocity were associated with significant BP reduction after RDN. Other factors, including higher baseline BP, hypertensive patients with orthostatic hypertension, BP variability, impaired cardiac baroreflex sensitivity, and some biomarkers are also reported to be associated with a better BP response to RDN.

Asunto(s)

Presión Sanguínea , Hipertensión , Riñón , Humanos , Hipertensión/fisiopatología , Hipertensión/cirugía , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Riñón/inervación , Riñón/fisiopatología , Presión Sanguínea/fisiología , Resultado del Tratamiento , Simpatectomía/métodos , Frecuencia Cardíaca/fisiología , Análisis de la Onda del Pulso , Arteria Renal/inervación , Barorreflejo/fisiología

RESUMEN

BACKGROUND: Beat-to-beat blood pressure variability (BPV) is based on each heartbeat and represents a dynamic equilibrium process modulated by artery and cardiac involvement of pressure-receptive reflexes. To date, there remains a lack of prospective studies illustrating the clinical value of beat-to-beat BPV within 24 hours of acute ischemic stroke onset. METHODS AND RESULTS: This study prospectively monitored beat-to-beat blood pressure and heart rate in patients with acute ischemic stroke within 24 hours of onset using a noninvasive plethysmograph and calculated beat-to-beat BPV, heart rate variability, and the cross-correlation baroreflex sensitivity. A modified Rankin Scale score of ≥2 at 90 days was defined as an unfavorable prognosis. Multivariate logistic regression was performed, and the nomogram model was developed by adding the beat-to-beat BPV to the traditional model for predicting prognosis. Beat-to-beat BPV increased significantly in the unfavorable outcome group (P<0.05) compared with that in the favorable outcome group, whereas no difference was observed in beat-to-beat heart rate variability and cross-correlation baroreflex sensitivity between both groups (P>0.05). Furthermore, beat-to-beat BPV within 24 hours of acute ischemic stroke onset was independently associated with unfavorable outcome at 90 days (P<0.005). The addition of beat-to-beat BPV to the traditional model for predicting prognosis enhanced the area under the receiver operating characteristic curve from 0.816 to 0.830. CONCLUSIONS: Increased beat-to-beat BPV within 24 hours of acute ischemic stroke onset was independently associated with a poor prognosis at 90 days and may be a potential predictor for discriminating unfavorable prognosis.

Asunto(s)

Barorreflejo , Presión Sanguínea , Frecuencia Cardíaca , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Presión Sanguínea/fisiología , Frecuencia Cardíaca/fisiología , Anciano , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/diagnóstico , Pronóstico , Barorreflejo/fisiología , Estudios Prospectivos , Persona de Mediana Edad , Factores de Tiempo , Valor Predictivo de las Pruebas , Nomogramas , Pletismografía , Anciano de 80 o más Años , Estado Funcional

RESUMEN

The sympathetic nervous system is critical for regulating blood pressure (BP) via the arterial baroreflex and sympathetic transduction in the peripheral vasculature. These mechanisms interact, and both may be altered with aging and impacted by menopause. Although age-related decreases in sympathetic transduction have been demonstrated in women, it remains unclear whether sympathetic baroreflex sensitivity (BRS) is impaired in postmenopausal women (POST). We tested the hypothesis that sympathetic BRS would be enhanced in POST compared with premenopausal women (PRE). We examined beat-by-beat BP and muscle sympathetic nerve activity (MSNA) in 19 PRE (22 ± 2 yr, 22 ± 3 kg/m2) and 12 POST (57 ± 5 yr, 24 ± 2 kg/m2) during 10 min of rest. Spontaneous sympathetic BRS was quantified as the slope of a linear regression between MSNA burst incidence and diastolic BP. Sympathetic transduction to mean arterial pressure (MAP) for the 10 cardiac cycles following spontaneous MSNA bursts was assessed via signal averaging method. Resting MAP was similar (PRE: 82 ± 8 vs. POST: 85 ± 8 mmHg, P = 0.43), whereas resting MSNA was elevated in POST (PRE: 10 ± 6 vs. POST: 45 ± 16 bursts/100 heart beats, P < 0.0001). Spontaneous sympathetic BRS was enhanced in POST (PRE: -2.0 ± 1.2 vs. POST: -5.2 ± 1.9 bursts/beat/mmHg, P < 0.0005). Sympathetic transduction to MAP was attenuated in POST (time: P < 0.001, group: P < 0.001, interaction: P < 0.01). These data suggest that sympathetic BRS may be enhanced in POST. Consistent with recent hypotheses, enhanced sensitivity of the arterial baroreflex's neural arc may signify a compensatory response to reduced efficiency of the peripheral arterial baroreflex arc (i.e., sympathetic transduction) to preserve BP buffering capacity.NEW & NOTEWORTHY Studies examining sympathetic baroreflex function with aging remain equivocal, with some studies showing an increase, decrease, or no change in sympathetic baroreflex sensitivity (BRS) in older adults compared with younger adults. With aging, women experience unique physiological changes due to menopause that influence autonomic function. For the first time, we show that postmenopausal women exhibit a greater sympathetic BRS compared with young premenopausal women.

Asunto(s)

Barorreflejo , Presión Sanguínea , Posmenopausia , Sistema Nervioso Simpático , Humanos , Barorreflejo/fisiología , Femenino , Sistema Nervioso Simpático/fisiología , Posmenopausia/fisiología , Persona de Mediana Edad , Presión Sanguínea/fisiología , Adulto , Adulto Joven , Frecuencia Cardíaca/fisiología , Premenopausia/fisiología , Presión Arterial/fisiología

Asunto(s)

Barorreflejo , Hemodinámica , Barorreflejo/fisiología , Humanos , Hemodinámica/fisiología , Animales , Ejercicio Físico/fisiología , Consumo de Oxígeno/fisiología

RESUMEN

OBJECTIVES: To evaluate the determinants of orthostatic hypotension (OH) in type 2 diabetes (T2D) and the usefulness of Δheart rate (HR)/Δsystolic blood pressure (SBP), index of cardiac baroreflex function, in identifying neurogenic OH. METHODS: In 208 participants with T2D, we diagnosed early cardiovascular autonomic neuropathy (CAN) and confirmed CAN according to 1 and 2 HR-based cardiovascular reflex tests (HR-CARTs). Through OH test we defined OH as SBP falls of ≥20 and ≥30 mm Hg with supine SBPs of <140 and ≥140 mm Hg, respectively. In participants with OH, we used the lying-to-standing and OH test and its diagnostic accuracy for neurogenic OH (as OH plus confirmed HR-CAN). RESULTS: OH was present in 25 participants and associated with lower HR-CART scores, higher glycosylated hemoglobin level, the presence of CAN, retinopathy, and peripheral vascular disease, the absence of hypertension, and physical activity (all, P < .05) but not with interfering drugs and ß-blockers. In a multiple logistic regression, HR-CAN was the main determinant of OH (odds ratio, 4.74) with physical activity and hypertension (odds ratios, 0.16 and 0.23; R2 = 0.22). ΔHR/ΔSBP had a good diagnostic accuracy for neurogenic OH (area under the receiver operating characteristic curve, 0.816 ± 0.087) and, at the cutoff of 0.5 bpm/mm Hg, a sensitivity of 100% and specificity of 63.2%. CONCLUSION: CAN remains the primary determinant of OH in T2D but does not explain all its variance. The index ΔHR/ΔSBP may represent a useful clinical tool to identify neurogenic OH.

Asunto(s)

Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Frecuencia Cardíaca , Hipotensión Ortostática , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/fisiopatología , Hipotensión Ortostática/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Frecuencia Cardíaca/fisiología , Neuropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/etiología , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/etiología

RESUMEN

In resistant hypertensive patients acute carotid baroreflex stimulation is associated with a blood pressure (BP) reduction, believed to be mediated by a central sympathoinhbition.The evidence for this sympathomodulatory effect is limited, however. This meta-analysis is the first to examine the sympathomodulatory effects of acute carotid baroreflex stimulation in drug-resistant and uncontrolled hypertension, based on the results of microneurographic studies. The analysis included 3 studies assessing muscle sympathetic nerve activity (MSNA) and examining 41 resistant uncontrolled hypertensives. The evaluation included assessment of the relationships between MSNA and clinic heart rate and BP changes associated with the procedure. Carotid baroreflex stimulation induced an acute reduction in clinic systolic and diastolic BP which achieved statistical significance for the former variable only [systolic BP: -19.98 mmHg (90% CI, -30.52, -9.43), P < 0.002], [diastolic BP: -5.49 mmHg (90% CI, -11.38, 0.39), P = NS]. These BP changes were accompanied by a significant MSNA reduction [-4.28 bursts/min (90% CI, -8.62, 0.06), P < 0.07], and by a significant heart rate decrease [-3.65 beats/min (90% CI, -5.49, -1.81), P < 0.001]. No significant relationship was detected beween the MSNA, systolic and diastolic BP changes induced by the procedure, this being the case also for heart rate. Our data show that the acute BP lowering responses to carotid baroreflex stimulation, although associated with a significant MSNA reduction, are not quantitatively related to the sympathomoderating effects of the procedure. This may suggest that these BP effects depend only in part on central sympathoinhibition, at least in the acute phase following the intervention.

Asunto(s)

Barorreflejo , Presión Sanguínea , Hipertensión , Presorreceptores , Sistema Nervioso Simpático , Humanos , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Seno Carotídeo/inervación , Terapia por Estimulación Eléctrica/métodos , Frecuencia Cardíaca/fisiología , Hipertensión/fisiopatología , Hipertensión/terapia , Presorreceptores/fisiología , Sistema Nervioso Simpático/fisiopatología , Sistema Nervioso Simpático/fisiología

RESUMEN

Orthostatic hypotension (OH) is a form of orthostatic intolerance (OI) and a key physiological indicator of autonomic dysfunction that is associated with an increased risk of major cerebrocardiovascular events. Symptoms of cerebral hypoperfusion have been reported in patients with OH, which worsens symptoms and increases the risk of syncope. Since pharmacological interventions increase blood pressure (BP) independent of posture and do not restore normal baroreflex control, nonpharmacological treatments are considered the foundation of OH management. While reductions in cerebral blood flow velocity (CBFv) during orthostatic stress are associated with a decrease in end-tidal CO2 (EtCO2) and hypocapnia in patients with OI, their contribution to the severity of OH is not well understood. These measures have been physiological targets in a wide variety of biofeedback interventions. This study explored the relationship between cardiovascular autonomic control, EtCO2 and cerebral hypoperfusion in patients (N = 72) referred for OI. Patients with systolic OH were more likely to be male, older, demonstrate reduced adrenal and vagal baroreflex sensitivity, and reduced cardiovagal control during head-up tilt (HUT) than patients without systolic OH. Greater reduction in CBFv during HUT was associated with a larger reduction in ETCO2 and systolic BP during HUT. While deficits in cardiovascular autonomic control played a more important role in systolic OH, reduced EtCO2 was a major contributor to orthostatic cerebral hypoperfusion. These findings suggest that biofeedback treatments targeting both the autonomic nervous system and EtCO2 should be part of nonpharmacological interventions complementing the standard of care in OH patients with symptoms of cerebral hypoperfusion.

Asunto(s)

Barorreflejo , Circulación Cerebrovascular , Hipotensión Ortostática , Humanos , Hipotensión Ortostática/terapia , Hipotensión Ortostática/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Barorreflejo/fisiología , Circulación Cerebrovascular/fisiología , Presión Sanguínea/fisiología , Adulto , Anciano , Sistema Nervioso Autónomo/fisiopatología , Biorretroalimentación Psicológica/métodos , Hipocapnia/fisiopatología , Hipocapnia/terapia

RESUMEN

The time course for recovery after anesthesia is poorly described for tricaine methanesulfonate (MS-222). We suggest that the baroreflex and the heart rate variability (HRV) could be used to index the recovery of the autonomic modulation after anesthesia. We analyzed the recovery profile of behavioral and physiological parameters over time to analyze the progression of recovery after anesthesia of American bullfrogs with MS-222. Mean heart rate stabilized after 17 h, whereas the baroreflex efficiency index took 23 h and the baroreflex operating gain, 29 h. Mean arterial pressure recovered after 26 h. Power spectral density peaked at 23 h and again after 40 h. Baroreflex was a relevant component of the first phase of HRV, while autonomic modulation for resting may take longer than 40 h. We suggest that physiological recovery is a complex phenomenon with multiple progressive phases, and the baroreflex may be a useful tool to observe the first substantial recovery of post-instrumentation capacity for autonomic modulation.

Asunto(s)

Aminobenzoatos , Sistema Nervioso Autónomo , Barorreflejo , Frecuencia Cardíaca , Rana catesbeiana , Animales , Barorreflejo/fisiología , Frecuencia Cardíaca/fisiología , Sistema Nervioso Autónomo/fisiología , Rana catesbeiana/fisiología , Aminobenzoatos/farmacología , Anestesia , Masculino , Presión Sanguínea/fisiología , Anestésicos/farmacología

RESUMEN

Contemporary discussion of the baroreflex includes the efferent vascular-sympathetic and cardiovagal arms. Since sympathetic postganglionic neurons also innervate the left ventricle (LV), it is often assumed that the LV produces a sympathetically mediated increase in contractility during baroreceptor unloading, but this has not been characterized using a load-independent index of contractility. We aimed to determine 1) whether LV contractility increases in response to baroreceptor unloading and 2) whether such increases are mediated via the sympathetic or parasympathetic arm of the autonomic nervous system. Ten male Wistar rats were anesthetized (urethane) and instrumented with arterial and LV pressure-volume catheters to measure mean arterial pressure (MAP) and load-independent LV contractility [maximal rate of increase in pressure adjusted to end-diastolic volume (PAdP/dtmax)], respectively. Rats were placed in a servo-controlled lower-body negative pressure (LBNP) chamber to reduce MAP by 10% for 60 s to mechanically unload baroreceptors under control conditions. LBNP was repeated in each animal following infusions of cardiac autonomic blockers using esmolol (sympathetic), atropine (parasympathetic), and esmolol + atropine. Under control conditions, PAdP/dtmax increased during baroreceptor unloading (26 ± 6 vs. 31 ± 9 mmHg·s-1·µL-1, P = 0.031). During esmolol, there was no increase in LV contractility during baroreceptor unloading (11 ± 2 vs. 12 ± 2, P = 0.125); however, during atropine, there was an increase in LV contractility during baroreceptor unloading (26 ± 6 vs. 31 ± 9, P = 0.019). During combined esmolol and atropine, there was a small increase in contractility versus control (13 ± 3 vs. 15 ± 4, P = 0.046). Our results demonstrate that, in anesthetized rats, LV contractility increases in response to baroreceptor unloading, which is largely sympathetically mediated.NEW & NOTEWORTHY This study empirically demonstrates a sympathetically mediated increase in LV contractility in response to baroreceptor unloading using a load-independent index of cardiac contractility in the anesthetized rat.

Asunto(s)

Barorreflejo , Ventrículos Cardíacos , Contracción Miocárdica , Presorreceptores , Ratas Wistar , Sistema Nervioso Simpático , Función Ventricular Izquierda , Animales , Masculino , Contracción Miocárdica/fisiología , Contracción Miocárdica/efectos de los fármacos , Ratas , Presorreceptores/fisiología , Presorreceptores/efectos de los fármacos , Barorreflejo/fisiología , Barorreflejo/efectos de los fármacos , Sistema Nervioso Simpático/fisiología , Sistema Nervioso Simpático/efectos de los fármacos , Ventrículos Cardíacos/efectos de los fármacos , Función Ventricular Izquierda/fisiología , Función Ventricular Izquierda/efectos de los fármacos , Presión Sanguínea/fisiología , Presión Sanguínea/efectos de los fármacos , Presión Arterial/fisiología , Presión Arterial/efectos de los fármacos , Atropina/farmacología , Anestesia , Propanolaminas

RESUMEN

PURPOSE: The specific characteristics of autonomic involvement in patients with early Parkinson's disease (PD) are unclear. This study aimed to evaluate the characteristics of autonomic dysfunction in drug-naïve patients with early-stage PD without orthostatic hypotension (OH) by analyzing Valsalva maneuver (VM) parameters. METHODS: We retrospectively analyzed drug-naïve patients without orthostatic hypotension (n = 61) and controls (n = 20). The patients were subcategorized into early PD (n = 35) and mid-PD (n = 26) groups on the basis of the Hoehn and Yahr staging. VM parameters, including changes in systolic blood pressure at late phase 2 (∆SBPVM2), ∆HRVM3, Valsalva ratio (VR), pressure recovery time, adrenergic baroreflex sensitivity, and vagal baroreflex sensitivity, were assessed. RESULTS: In the early PD group, ∆SBPVM2, a marker of sympathetic function, was significantly lower compared with that in controls (risk ratio = 0.95, P = 0.027). Receiver operating characteristic (ROC) curve analysis showed an optimal cut-off value of -10 mmHg for ∆SBPVM2 [P = 0.002, area under the curve (AUC): 0.737]. VR exhibited an inverse relationship with Unified Parkinson's Disease Rating Scale Part 3 scores in the multivariable regression analysis (VR: P = 0.038, ß = -28.61), whereas age showed a positive relationship (age: P = 0.027, ß = 0.35). CONCLUSION: The ∆BPVM2 parameter of the VM may help detect autonomic nervous system involvement in early-PD without OH. Our results suggest that sympathetic dysfunction is an early manifestation of autonomic dysfunction in patients with PD.

Asunto(s)

Enfermedades del Sistema Nervioso Autónomo , Barorreflejo , Enfermedad de Parkinson , Maniobra de Valsalva , Humanos , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Masculino , Femenino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/etiología , Maniobra de Valsalva/fisiología , Barorreflejo/fisiología , Sistema Nervioso Simpático/fisiopatología , Presión Sanguínea/fisiología

RESUMEN

OBJECTIVE: We investigated the systemic arterial hypertension effects on cardiovascular autonomic modulation and baroreflex sensitivity (BRS) in women with or without preserved ovarian function. METHODS: A total of 120 women were allocated into two groups: middle-aged premenopausal women (42 ± 3 y old; n = 60) and postmenopausal women (57 ± 4 y old; n = 60). Each group was also divided into two smaller groups (n = 30): normotensive and hypertensive. We evaluated hemodynamic and anthropometric parameters, cardiorespiratory fitness, BRS, heart rate variability (HRV), and blood pressure variability. The effects of hypertension and menopause were assessed using a two-way analysis of variance. Post hoc comparisons were performed using the Student-Newman-Keuls test. RESULTS: Comparing premenopausal groups, women with systemic arterial hypertension showed lower BRS (9.1 ± 4.4 vs 13.4 ± 4.2 ms/mm Hg, P < 0.001 ) and HRV total variance (1,451 ± 955 vs 2,483 ± 1,959 ms 2 , P = 0.005) values than normotensive; however, the vagal predominance still remained. On the other hand, both postmenopausal groups showed an expressive reduction in BRS (8.3 ± 4.2 vs 11.3 ± 4.8 ms/mm Hg, P < 0.001) and HRV characterized by sympathetic modulation predominance (low-frequency oscillations; 56% ± 17 vs 44% ± 17, P < 0.001), in addition to a significant increase in blood pressure variability variance (28.4 ± 14.9 vs 22.4 ± 12.5 mm Hg 2 , P = 0.015) compared with premenopausal groups. Comparing both postmenopausal groups, the hypertensive group had significantly lower values ​​of HRV total variance (635 ± 449 vs 2,053 ± 1,720 ms 2 , P < 0.001) and BRS (5.3 ± 2.8 vs 11.3 ± 3.2 ms/mm Hg) than the normotensive. CONCLUSIONS: Hypertensive middle-aged premenopausal women present HRV autonomic modulation impairment, but they still maintain a vagal predominance. After menopause, even normotensive women show sympathetic autonomic predominance, which may also be associated with aging. Furthermore, postmenopausal women with hypertension present even worse cardiac autonomic modulation.

Asunto(s)

Sistema Nervioso Autónomo , Barorreflejo , Presión Sanguínea , Frecuencia Cardíaca , Hipertensión , Menopausia , Posmenopausia , Premenopausia , Humanos , Femenino , Persona de Mediana Edad , Hipertensión/fisiopatología , Adulto , Barorreflejo/fisiología , Frecuencia Cardíaca/fisiología , Sistema Nervioso Autónomo/fisiopatología , Sistema Nervioso Autónomo/fisiología , Presión Sanguínea/fisiología , Menopausia/fisiología , Posmenopausia/fisiología , Premenopausia/fisiología , Sistema Cardiovascular/fisiopatología , Capacidad Cardiovascular/fisiología

RESUMEN

AIMS: Carotid baroreflex activation therapy (BAT) restores baroreflex sensitivity and modulates the imbalance in cardiac autonomic function in patients with heart failure with reduced ejection fraction (HFrEF). We tested the hypothesis that treatment with BAT significantly reduces cardiovascular mortality and heart failure morbidity and provides long-term safety and sustainable symptomatic improvement. METHODS AND RESULTS: BeAT-HF was a prospective, multicentre, randomized, two-arm, parallel-group, open-label, non-implanted control trial. New York Heart Association (NYHA) class III subjects, ejection fraction ≤35%, previous heart failure hospitalization or N-terminal pro-B-type natriuretic peptide (NT-proBNP) >400 pg/ml, no class I indication for cardiac resynchronization therapy and NT-proBNP <1600 pg/ml were randomized to BAT plus optimal medical management (BAT group) or optimal medical management alone (control). The primary endpoint was cardiovascular mortality and HF morbidity; additional pre-specified endpoints included durability of safety, quality of life (QOL), exercise capacity (6-min hall walk distance [6MHWD]), functional status (NYHA class), hierarchical composite win ratio, freedom from all-cause death, left ventricular assists device (LVAD) implantation, heart transplant. Overall, 323 patients had 332 primary events, median follow-up was 3.6 years/patient. Both primary endpoint (rate ratio 0.94, 95% confidence interval [CI] 0.57-1.57; p = 0.82) and components of the primary endpoints were not significantly different between BAT and control. The system- and procedure-related major adverse neurological and cardiovascular event-free rate remained 97% throughout the trial. Symptom improvement (QOL, 6MHWD, NYHA class, all nominal p < 0.001) in the BAT group was durable in time, sustainable in extent. Win ratio (1.26, 95% CI 1.02-1.58) and freedom from all-cause death, LVAD implantation, heart transplant (hazard ratio 0.66, 95% CI 0.43-1.01) favoured the BAT group but did not reach statistical significance. CONCLUSION: The BeAT-HF primary endpoint was neutral; however, BAT provided safe, effective, and sustainable improvements in HFrEF patient's functional status, 6MHWD and QOL.

Asunto(s)

Barorreflejo , Insuficiencia Cardíaca , Calidad de Vida , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/fisiopatología , Masculino , Femenino , Volumen Sistólico/fisiología , Barorreflejo/fisiología , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Resultado del Tratamiento , Péptido Natriurético Encefálico/sangre , Terapia por Estimulación Eléctrica/métodos , Tolerancia al Ejercicio/fisiología , Estudios de Seguimiento

RESUMEN

In the absence of a true gold standard for non-invasive baroreflex sensitivity estimation, it is difficult to quantify the accuracy of the variety of techniques used. A popular family of methods, usually entitled 'sequence methods' involves the extraction of (apparently) correlated sequences from blood pressure and RR-interval data and the subsequent fitting of a regression line to the data. This paper discusses the accuracy of sequence methods from a system identification perspective, using both data generated from a known mathematical model and spontaneous baroreflex data. It is shown that sequence methods can introduce significant bias in the baroreflex sensitivity estimate, even when great care is taken in sequence selection.

Asunto(s)

Barorreflejo , Presión Sanguínea , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Humanos , Frecuencia Cardíaca/fisiología

RESUMEN

PURPOSE: We hypothesised that during a rest-to-exercise transient in hypoxia (H), compared to normoxia (N), (i) the initial baroreflex sensitivity (BRS) decrease would be slower and (ii) the fast heart rate (HR) and cardiac output (CO) response would have smaller amplitude (A1) due to lower vagal activity in H than N. METHODS: Ten participants performed three rest-to-50 W exercise transients on a cycle-ergometer in N (ambient air) and three in H (inspired fraction of O2 = 0.11). R-to-R interval (RRi, by electrocardiography) and blood pressure profile (by photo-plethysmography) were recorded non-invasively. Analysis of the latter provided mean arterial pressure (MAP) and stroke volume (SV). CO = HR·SV. BRS was calculated by modified sequence method. RESULTS: Upon exercise onset in N, MAP fell to a minimum (MAPmin) then recovered. BRS decreased immediately from 14.7 ± 3.6 at rest to 7.0 ± 3.0 ms mmHg-1 at 50 W (p < 0.01). The first BRS sequence detected at 50 W was 8.9 ± 4.8 ms mmHg-1 (p < 0.05 vs. rest). In H, MAP showed several oscillations until reaching a new steady state. BRS decreased rapidly from 10.6 ± 2.8 at rest to 2.9 ± 1.5 ms mmHg-1 at 50 W (p < 0.01), as the first BRS sequence at 50 W was 5.8 ± 2.6 ms mmHg-1 (p < 0.01 vs. rest). CO-A1 was 2.96 ± 1.51 and 2.31 ± 0.94 l min-1 in N and H, respectively (p = 0.06). HR-A1 was 7.7 ± 4.6 and 7.1 ± 5.9 min-1 in N and H, respectively (p = 0.81). CONCLUSION: The immediate BRS decrease in H, coupled with similar rapid HR and CO responses, is compatible with a withdrawal of residual vagal activity in H associated with increased sympathetic drive.

Asunto(s)

Barorreflejo , Ejercicio Físico , Frecuencia Cardíaca , Hipoxia , Descanso , Humanos , Barorreflejo/fisiología , Masculino , Hipoxia/fisiopatología , Ejercicio Físico/fisiología , Adulto , Frecuencia Cardíaca/fisiología , Descanso/fisiología , Presión Sanguínea/fisiología , Femenino , Gasto Cardíaco/fisiología