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1.
High Blood Press Cardiovasc Prev ; 27(1): 93-101, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32048202

RESUMEN

INTRODUCTION: Orthostatic hypotension (OH) and atrial fibrillation (AF) are both regarded as independent risk factors for transient ischemic attack (TIA). However, the clinical implication of OH in the presence of AF is unclear. This study investigates, for the first time, the association between blood pressure (BP), OH and mortality in a cohort of patients with AF and TIA symptoms. AIM: To investigate the incidence of the association between OH, AF and TIA. METHODS: This retrospective observational study utilised the Leicester one-stop transient TIA clinic patient database to consider the initial systolic and diastolic BP of 688 patients with a diagnosis of AF. The primary outcome was time until death. Covariant measures included status of AF diagnosis (known or new AF), cardiovascular risk factors, and primary clinic diagnosis [cerebrovascular (CV) versus non-cerebrovascular (non-CV)]. Statistical models adjusted for sex, age, previous AF diagnosis. RESULTS: Mortality rate was higher in the over 85 age group [191.5 deaths per 1000 person years (py) (95% CI 154.0-238.1)] and lower in the aged 75 and younger age group [40.0 deaths per 1000 py (95% CI 27.0-59.2)] compared to intermediate groups. A 10 mmHg increase in supine diastolic BP was associated with a significant reduction in the hazard of mortality for patients suspected of TIA with AF [adjusted HR 0.79 (95% CI 0.68-0.92), p < 0.001]. The mortality rate for patients with OH was 119.0 deaths per 1000 py compared with a rate of 98.0 for patients without OH (rate ratio 1.2, p = 0.275). CONCLUSION: Higher diastolic BP may be a marker for reduced mortality risk in patients with a previous AF diagnosis and non-CV diagnosis. Lower diastolic BP and the presence of AF pertain to a higher mortality risk. This study raises the importance of opportunistic screening for both OH and AF in patients presenting to TIA clinic.


Asunto(s)
Fibrilación Atrial/epidemiología , Hipotensión Ortostática/epidemiología , Ataque Isquémico Transitorio/epidemiología , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/mortalidad , Fibrilación Atrial/fisiopatología , Presión Sanguínea , Inglaterra/epidemiología , Femenino , Frecuencia Cardíaca , Humanos , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/mortalidad , Hipotensión Ortostática/fisiopatología , Incidencia , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/mortalidad , Ataque Isquémico Transitorio/fisiopatología , Masculino , Estudios Retrospectivos , Factores de Riesgo
2.
Adv Exp Med Biol ; 1232: 77-83, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31893397

RESUMEN

Instantaneous orthostatic hypotension (INOH) is one of the main types of orthostatic dysregulation in children and adolescents. In patients with INOH arterial pressure drops considerably after active standing and is slow to recover. We investigated changes in cerebral oxygenation in the bilateral prefrontal cortex during an active standing test in juvenile INOH patients to evaluate changes in cerebral oxygen metabolism. We enrolled 82 INOH patients (mean age 13.8 ± 2.2 years, 52 mild and 30 severe patients) at Nihon University Itabashi Hospital from October 2013 to April 2018. We measured cerebral oxygenated hemoglobin, deoxygenated hemoglobin, and total hemoglobin levels in the bilateral prefrontal cortex using near-infrared spectroscopy during an active standing test. In severe INOH patients, cerebral oxygenation of the right prefrontal cortex remained constant when blood pressure dropped; however, de-oxy-Hb significantly increased. These findings confirm that there is asymmetrical autoregulation between the right and left prefrontal cortex.


Asunto(s)
Circulación Cerebrovascular , Hipotensión Ortostática , Adolescente , Circulación Cerebrovascular/fisiología , Niño , Homeostasis , Humanos , Hipotensión Ortostática/fisiopatología , Oxihemoglobinas , Espectroscopía Infrarroja Corta
3.
Neurology ; 93(16): e1526-e1534, 2019 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-31527282

RESUMEN

OBJECTIVE: To determine the frequency, evolution, and associated features of orthostatic hypotension (OH) over 7 years of prospective follow-up in a population-based, initially drug-naive Parkinson disease (PD) cohort. METHODS: We performed repeated lying and standing blood pressure measurements in 185 patients with newly diagnosed PD and 172 matched normal controls to determine the occurrence of (1) OH using consensus-based criteria and (2) clinically significant OH (mean arterial pressure in standing position ≤75 mm Hg). We applied generalized estimating equations models for correlated data to investigate associated features of these 2 outcomes in patients with PD. RESULTS: OH was more common in patients with PD than controls at all visits, with the relative risk increasing from 3.0 (95% confidence interval [CI] 1.6-5.8; p < 0.001) at baseline to 4.9 (95% CI 2.4-10.1; p < 0.001) after 7 years. Despite a high cumulative prevalence of OH (65.4%) and clinically significant OH (29.2%), use of antihypotensive drugs was very rare (0.5%). OH was independently associated with older age (odds ratio [OR] 1.06 per year; 95% CI 1.03-1.10), lower Mini-Mental State Examination score (OR 0.91 [0.85-0.97] per unit), and longer follow-up time (OR 1.12 [1.03-1.23] per year). Clinically significant OH was associated with the same characteristics, in addition to higher levodopa equivalent dosage (OR 1.16 [1.07-1.25] per 100 mg). CONCLUSIONS: In this population-based study, we found OH to be a very frequent but undertreated complication in early PD, with associations to both disease-specific symptoms and drug treatment. Our findings suggest that clinicians should more actively assess and manage OH abnormalities in PD.


Asunto(s)
Presión Sanguínea/fisiología , Hipotensión Ortostática/fisiopatología , Enfermedad de Parkinson/fisiopatología , Factores de Edad , Anciano , Anciano de 80 o más Años , Presión Sanguínea/efectos de los fármacos , Femenino , Estudios de Seguimiento , Humanos , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/tratamiento farmacológico , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Estudios Prospectivos , Índice de Severidad de la Enfermedad
4.
Neurology ; 93(14): e1339-e1347, 2019 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-31484717

RESUMEN

OBJECTIVE: To evaluate the pattern and severity of autonomic dysfunction in autopsy-confirmed progressive supranuclear palsy (PSP) compared to α-synuclein pathology. METHODS: Autopsy-confirmed cases of 14 patients with PSP, 18 with multiple system atrophy (MSA), and 24 with Lewy body disease (LBD) with antemortem autonomic testing were reviewed retrospectively. All patients underwent comprehensive clinical evaluations by a movement disorder specialist, formal autonomic testing, and postmortem examinations at Mayo Clinic. RESULTS: The absence of orthostatic hypotension (OH) was the strongest autonomic parameter that distinguished PSP from α-synucleinopathies (0% vs 69%, p < 0.0001). Tests of adrenergic failure, which distinguish neurogenic OH, also differentiated PSP from other groups. These included the pressure recovery time (p = 0.0008), adrenergic impairment score (p = 0.001), and magnitude of change of systolic (p = 0.0002) and diastolic (p = 0.0001) blood pressures (BPs) during upright tilt. In addition, REM sleep behavior disorder was seen less frequently (p = 0.006) in PSP (33%) compared to MSA (87%) and LBD (90%). Antemortem clinical diagnostic accuracy for these phenotypically variable disorders was 57% for PSP and 83% for α-synucleinopathies. CONCLUSION: Our results suggest that the cardiovascular adrenergic system, which sustains BP during standing, is relatively unaffected, if not spared, in PSP. These findings increase our understanding of the clinical signature of PSP and have the potential to improve diagnostic accuracy in atypical parkinsonisms by distinguishing PSP from the α-synucleinopathies.


Asunto(s)
Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/fisiopatología , Parálisis Supranuclear Progresiva/diagnóstico , Parálisis Supranuclear Progresiva/fisiopatología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
5.
BMJ Case Rep ; 12(8)2019 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-31434666

RESUMEN

A 62-year-old man presented with a 2-year history of syncope, collapse and fluctuating blood pressure (BP). His medications included midodrine (10 mg, three times per day) and fludrocortisone (0.1 mg, two times per day), but neither treatment afforded symptomatic relief. Autonomic testing was performed. Head-up tilt table testing revealed a supine BP of 112/68 mm Hg (heart rate, 74 beats per minute (bpm)) after 6 min, which dropped to 76/60 mm Hg (83 bpm) within 2 min of 80° head-up tilt. Findings from a heart rate with deep breathing test and a Valsalva test were consistent with autonomic dysfunction. The patient was diagnosed with neurogenic orthostatic hypotension and treated with droxidopa (100 mg, two times per day; titrated to 100 mg, one time per day). After initiating treatment with droxidopa, the patient no longer reported losing consciousness on standing and experienced improvement in activities of daily living. These improvements were maintained through 1 year of follow-up.


Asunto(s)
Antiparkinsonianos/uso terapéutico , Sistema Nervioso Autónomo/fisiopatología , Droxidopa/uso terapéutico , Hipotensión Ortostática/diagnóstico , Síncope/etiología , Pruebas de Mesa Inclinada , Accidentes por Caídas , Actividades Cotidianas , Humanos , Hipotensión Ortostática/tratamiento farmacológico , Hipotensión Ortostática/fisiopatología , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
7.
Physiol Int ; 106(3): 236-249, 2019 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-31304761

RESUMEN

BACKGROUND: Premenopausal women show a higher incidence of orthostatic hypotension than age-matched men, but there are limited data available on sex differences in cardiovascular responses to orthostatic challenge in healthy older persons. We investigated sex differences in hemodynamic and autonomic responses to orthostatic challenge in healthy older males and females. MATERIALS AND METHODS: Fourteen older healthy women and 10 age-matched men performed a sit-to-stand test (5 min of sitting followed by 5 min of standing). A Task Force® Monitor continuously measured the following beat-to-beat hemodynamic parameters: heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure, stroke index, cardiac index, and total peripheral resistance index. Cardiac autonomic activity, low-frequency (LF: 0.04-0.15 Hz) normalized (LFnuRRI) and high-frequency (HF: 0.15-0.4 Hz) normalized (HFnuRRI) components, and the ratio between LF and HF power (LF/HF) were calculated using power spectral analysis of heart rate variability. RESULTS: Across all hemodynamic parameters, there were no significant differences between the sexes at baseline and during standing. LFnuRRI (median: 70.2 vs. 52.3, p < 0.05) and LF/HF ratio (median: 2.4 vs. 1.1, p < 0.05) were significantly higher, whereas HFnuRRI (median: 29.8 vs. 47.7, p < 0.05) was lower among women at baseline. All other heart rate variability measures did not differ between the sexes. CONCLUSIONS: The data indicate that older women showed higher sympathetic and lower parasympathetic activity at rest compared to age-matched men. These results are contradictory to the observations from previous studies, which showed a reduced sympathetic and enhanced parasympathetic activity in women in all ages. Further studies are required to determine the underlying mechanisms contributing to higher incidence of orthostatic hypotension in older females.


Asunto(s)
Sistema Cardiovascular/patología , Anciano , Sistema Nervioso Autónomo/fisiología , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Femenino , Frecuencia Cardíaca/fisiología , Hemodinámica/fisiología , Humanos , Hipotensión Ortostática/fisiopatología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Caracteres Sexuales
8.
J Stroke Cerebrovasc Dis ; 28(8): 2124-2131, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31147254

RESUMEN

BACKGROUND: Orthostatic hypotension (OH) has been independently associated with increased risk of stroke and other cardiovascular events. We sought to investigate the relationship between OH at follow-up and recurrent stroke risk in SPS3 (Secondary Prevention of Small Subcortical Strokes) trial patient cohort. This is a retrospective cohort analysis. METHODS: We included all SPS3 trial participants with blood pressure measurements in both sitting and standing position per protocol at baseline, with at least 1 follow-up visit to establish the relationship between OH at follow-up and recurrent stroke risk (primary outcome). Secondary outcomes included major vascular events, myocardial infarction, all-cause mortality, and, ischemic and hemorrhagic stroke subtypes. Participants were classified as having OH at baseline and at each follow-up visit based on a systolic BP decline ≥20 mm Hg or a diastolic BP decline ≥10 mm Hg on position change from sitting to standing. We used Cox proportional hazards regression modeling to compare the risk of outcomes among those with and without OH. RESULTS: A total of 2275 patients were included with a mean follow up time 3.2 years (standard deviation = 1.6 years). 39% (881/2275) had OH at some point during their follow-up. Of these, 41% (366/881) had orthostatic symptoms accompanying the BP drop. In a fully adjusted model, those with OH had a 1.8 times higher risk of recurrent stroke than those without OH (95% confidence interval: 1.1-3.0). The risk of ischemic stroke, major vascular events, and all-cause mortality was similarly elevated among the OH group. CONCLUSION: OH was associated with increased recurrent stroke risk, vascular events, and all-cause death in this large cohort of lacunar stroke patients. Whether minimizing OH in the management of poststroke hypertension in patients with lacunar stroke reduces recurrent stroke risk deserves further study.


Asunto(s)
Presión Sanguínea , Hipotensión Ortostática/complicaciones , Prevención Secundaria/métodos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Anciano , Causas de Muerte , Femenino , Humanos , Hipotensión Ortostática/mortalidad , Hipotensión Ortostática/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/fisiopatología , Factores de Tiempo , Resultado del Tratamiento
9.
Int J Mol Sci ; 20(10)2019 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-31109053

RESUMEN

Cognitive impairment following spinal cord injury (SCI) has received considerable attention in recent years. Among the various systemic effects of SCI that contribute towards cognitive decline in this population, cardiovascular dysfunction is arguably one of the most significant. The majority of individuals with a cervical or upper-thoracic SCI commonly experience conditions called orthostatic hypotension and autonomic dysreflexia, which are characterized by dangerous fluctuations in systemic blood pressure (BP). Herein, we review the potential impact of extreme BP lability on vascular cognitive impairment (VCI) in individuals with SCI. Albeit preliminary in the SCI population, there is convincing evidence that chronic hypotension and hypertension in able-bodied individuals results in devastating impairments in cerebrovascular health, leading to VCI. We discuss the pertinent literature, and while drawing mechanistic comparisons between able-bodied cohorts and individuals with SCI, we emphasize the need for additional research to elucidate the mechanisms of cognitive impairment specific to the SCI population. Lastly, we highlight the current and potential future therapies to manage and treat BP instability, thereby possibly mitigating VCI in the SCI population.


Asunto(s)
Presión Sanguínea , Vasos Sanguíneos/fisiopatología , Reflejo Anormal , Traumatismos de la Médula Espinal/fisiopatología , Animales , Disreflexia Autónoma/etiología , Disreflexia Autónoma/fisiopatología , Disreflexia Autónoma/terapia , Humanos , Hipotensión Ortostática/fisiopatología , Hipotensión Ortostática/terapia , Traumatismos de la Médula Espinal/etiología , Traumatismos de la Médula Espinal/terapia
10.
Neurol Res ; 41(8): 734-741, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31030628

RESUMEN

Objectives: This study was designed to investigate clinical symptoms and blood pressure (BP) characteristics in Parkinson's disease (PD) with orthostatic hypotension (OH), and to figure out the influencing factors of PD with OH (PD-OH). Methods: Total 150 PD patients were divided into PD-OH and PD with no OH (PD-NOH) groups based on BP value. Series of scales were used to evaluate clinical symptoms. Twenty-four-hour ambulatory BP monitoring was adopted. Results: Total 49 PD patients (32.67%) were with OH. PD-OH group had significantly older age, longer disease duration, more diabetes cases, higher levels of fasting blood glucose, higher levels of hemoglobin A1c (HbA1c) and higher levodopa-equivalent daily doses (P < 0.05). Motor symptoms and non-motor symptoms, including autonomic dysfunction, fatigue and cognitive impairment indicated by significantly changed scores of related scales were found in PD-OH group (P < 0.05). PD-OH group had increased BP variability (BPV) and a higher proportion of non-dipper BP pattern (P < 0.05). Binary logistic regression analysis showed that age (B, 0.064; 95% CI, 1.007 ~ 1.128; P < 0.05), HbA1c (B, 1.091; 95% CI, 1.158 ~ 7.648; P < 0.05), and systolic BPV (B, 0.138; 95% CI, 1.004 ~ 1.312; P < 0.05) were independent related factors for PD-OH group. The PD-OH group had significantly compromised daily activities and quality of life (P < 0.05). Conclusion: Older age, higher levels of HbA1c and increased systolic BPV were the influencing factors of PD-OH patients. Daily activities and quality of life of PD-OH patients were fairly compromised.


Asunto(s)
Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/fisiopatología , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/fisiopatología , Anciano , Presión Sanguínea , Femenino , Hemoglobina A Glucada/análisis , Humanos , Hipotensión Ortostática/complicaciones , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Factores de Riesgo
11.
BMC Geriatr ; 19(1): 80, 2019 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-30866845

RESUMEN

BACKGROUND: Orthostatic hypotension (OH; profound falls in blood pressure when upright) is a common deficit that increases in incidence with age, and may be associated with falling risk. Deficit accumulation results in frailty, regarded as enhanced vulnerability to adverse outcomes. We aimed to evaluate the relationships between OH, frailty, falling and mortality in elderly care home residents. METHODS: From the Minimum Data Set (MDS) document, a frailty index (FI-MDS) was generated from a list of 58 deficits, ranging from 0 (no deficits) to 1.0 (58 deficits). OH was evaluated from beat-to-beat blood pressure and heart rate (finger plethysmography) collected during a 15-min supine-seated orthostatic stress test. Retrospective and prospective falling rates (falls/year) were extracted from facility falls incident reports. All-cause 3-year mortality was determined. Data are reported as mean ± standard error. RESULTS: Data were obtained from 116 older adults (aged 84.2 ± 0.9 years; 44% males) living in two long term care facilities. The mean FI-MDS was 0.36 ± 0.01; FI-MDS was correlated with age (r = 0.277; p = 0.003). Those who were frail (FI ≥ 0.27) had larger Initial (- 17.8 ± 4.2 vs - 6.1 ± 3.3 mmHg, p = 0.03) and Consensus (- 22.7 ± 4.3 vs - 11.5 ± 3.3 mmHg, p = 0.04) orthostatic reductions in systolic arterial pressure. Frail individuals had higher prospective and retrospective falling rates and higher 3-year mortality. Receiver operating characteristic curves evaluated the ability of FI-MDS alone to predict prospective falls (sensitivity 72%, specificity 36%), Consensus OH (sensitivity 68%, specificity 60%) and 3-year mortality (sensitivity 77%, specificity 49%). Kaplan Meier survival analyses showed significantly higher 3-year mortality in those who were frail compared to the non-frail (p = 0.005). CONCLUSIONS: Frailty can be captured using a frailty index based on MDS data in elderly individuals living in long term care, and is related to susceptibility to orthostatic hypotension, falling risk and 3-year mortality. Use of the MDS to generate a frailty index may represent a simple and convenient risk assessment tool for older adults living in long term care. Older adults who are both frail and have impaired orthostatic blood pressure control have a particularly high risk of falling and should receive tailored management to mitigate this risk.


Asunto(s)
Accidentes por Caídas/mortalidad , Anciano Frágil , Hogares para Ancianos , Hipotensión Ortostática/mortalidad , Hipotensión Ortostática/fisiopatología , Anciano , Anciano de 80 o más Años , Presión Sanguínea/fisiología , Femenino , Fragilidad , Evaluación Geriátrica/métodos , Frecuencia Cardíaca/fisiología , Humanos , Hipotensión Ortostática/diagnóstico , Cuidados a Largo Plazo/métodos , Masculino , Estudios Prospectivos , Estudios Retrospectivos , Medición de Riesgo
12.
Neurosci Lett ; 703: 213-218, 2019 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-30904574

RESUMEN

STUDY DESIGN: observational study. OBJECTIVES: Heart rate variability (HRV) studies have shown that the low-frequency (LF) domain is decreased in postural challenge of spinal cord injury (SCI). However, there are inconsistencies in the literature regarding HRV with postural challenge. We believed that asymptomatic orthostatic hypotension (OH) may contribute to the discrepancies in the literature. We also evaluated the time-domain parameters of HRV to evaluate for changes in SCI postural challenge. We looked at the association of Frequency and Time-domain HRV parameters to blood pressure (BP) and postural challenge in SCI based on groups with and without OH. SETTING: SCI clinic. METHODS: Patients from SCI clinic were enrolled and 5-minute electrocardiogram (ECG) recordings were performed before and after a postural challenge from supine to sitting position with blood pressure (BP) recordings at each time point. Between and within group analyses were performed based on tetraplegia, paraplegia, and the presence of asymptomatic OH. RESULTS: There were 6 controls and 18 SCI subjects, 4 with OH based on change in diastolic BP. After postural challenge, mean heart rate was lower in tetraplegia compared to controls in all groupings. When OH was removed from the groups, total power was consistently reduced in tetraplegia compared to paraplegia across all positions. There were both time- and frequency-domain differences observed in SCI with OH compared to SCI without. CONCLUSIONS: Autonomic variability is increased in SCI with OH and can lead to misinterpretation of findings if asymptomatic OH is included in samples. Our data suggest that there are frequency- and time-domain differences in HRV variables in those with OH compared to those without. Future HRV studies should account for asymptomatic OH and include analyses of the time-domain variables in postural challenge of SCI.


Asunto(s)
Frecuencia Cardíaca , Hipotensión Ortostática/fisiopatología , Traumatismos de la Médula Espinal/fisiopatología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paraplejía/fisiopatología , Postura , Cuadriplejía/fisiopatología
13.
Hypertension ; 73(4): 910-918, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30798661

RESUMEN

Lewy body diseases involve neurogenic orthostatic hypotension (nOH), cardiac noradrenergic deficiency, and deposition of the protein AS (alpha-synuclein) in sympathetic ganglion tissue. Mechanisms linking these abnormalities are poorly understood. One link may be AS deposition within sympathetic neurons. We validated methodology to quantify AS colocalization with TH (tyrosine hydroxylase), a marker of sympathetic noradrenergic innervation, and assessed associations of AS/TH colocalization with myocardial norepinephrine content and cardiac sympathetic neuroimaging data in nOH. Postmortem sympathetic ganglionic AS/TH colocalization indices and myocardial norepinephrine contents were measured in 4 Lewy body and 3 rare non-Lewy body nOH patients. Sixteen Lewy body and 11 non-Lewy body nOH patients underwent in vivo skin biopsies and thoracic 18F-dopamine positron emission tomographic scanning, with cutaneous colocalization indices expressed versus cardiac 18F-dopamine-derived radioactivity. Ganglionic AS/TH colocalization indices were higher and myocardial norepinephrine lower in Lewy body than non-Lewy body nOH ( P=0.0020, P=0.014). The Lewy body nOH group had higher AS/TH colocalization indices in skin biopsies and lower myocardial 18F-dopamine-derived radioactivity than did the non-Lewy body nOH group ( P<0.0001 each). All Lewy body nOH patients had colocalization indices >1.5 in skin biopsies and 18F-dopamine-derived radioactivity <6000 nCi-kg/cc-mCi, a combination not seen in non-Lewy body nOH patients ( P<0.0001). In Lewy body nOH, AS deposition in sympathetic noradrenergic nerves is related to postmortem neurochemical and in vivo neuroimaging evidence of myocardial noradrenergic deficiency. These associations raise the possibility that intraneuronal AS deposition plays a pathophysiological role in the myocardial sympathetic neurodegeneration attending Lewy body nOH.


Asunto(s)
Neuronas Adrenérgicas/metabolismo , Hipotensión Ortostática/metabolismo , Cuerpos de Lewy/metabolismo , Miocardio/metabolismo , alfa-Sinucleína/metabolismo , Neuronas Adrenérgicas/patología , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Humanos , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/fisiopatología , Cuerpos de Lewy/patología , Masculino , Persona de Mediana Edad , Miocardio/patología , Tomografía de Emisión de Positrones , Piel/metabolismo , Piel/patología
14.
Eur J Appl Physiol ; 119(5): 1117-1125, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30771059

RESUMEN

PURPOSE: Cerebral oxygenation as measured by near-infrared spectroscopy (NIRS) might be useful to discriminate between physiological and pathological responses after standing up in individuals with orthostatic hypotension. This study addressed the physiological sensitivity of the cerebral oxygenation responses as measured by NIRS to different types and speeds of postural changes in healthy adults and assessed the reliability of these responses. METHODS: Cerebral oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb) and tissue saturation index (TSI) were measured bilaterally on the forehead of 15 healthy individuals (12 male, age range 18-27) using NIRS. Participants performed three repeats of sit to stand, and slow and rapid supine to stand movements. Responses were defined as the difference between mean, minimum and maximum O2Hb, HHb and TSI values after standing up and baseline. Test-retest, interobserver and intersensor reliabilities were addressed using intraclass correlation coefficients (ICCs). RESULTS: The minimum O2Hb response was most sensitive to postural changes and showed significant differences (- 4.09 µmol/L, p < 0.001) between standing up from sitting and supine position, but not between standing up at different speeds (- 0.31 µmol/L, p = 0.70). The minimum O2Hb response was the most reliable parameter (ICC > 0.6). CONCLUSIONS: In healthy individuals, NIRS-based cerebral oxygenation parameters are sensitive to postural change and discriminate between standing up from supine and sitting position with minimum O2Hb response as the most sensitive and reliable parameter. The results underpin the potential value for future clinical use of NIRS in individuals with orthostatic hypotension.


Asunto(s)
Encéfalo/metabolismo , Hipotensión Ortostática/fisiopatología , Consumo de Oxígeno , Oxihemoglobinas/análisis , Postura , Espectroscopía Infrarroja Corta/normas , Adolescente , Adulto , Femenino , Humanos , Masculino , Distribución Aleatoria , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
15.
Acta Diabetol ; 56(1): 39-43, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30159748

RESUMEN

AIMS: Cardiovascular autonomic testing is time consuming when adopting the entire Ewing battery of tests, hence, clinicians usually adopt an empirically reduced number of tests which may give controversial results. Our purpose was to examine the reliability of the cardiovascular tests most commonly used in autonomic diagnoses. METHODS: We tested 334 subjects, from an original group of 3745, who had shown an altered deep breathing test to both Lying to standing and Valsalva manoeuvre, assuming a value of postural hypotension of more than 15 mmHg as a sign of almost true dysautonomia. RESULTS: VM showed the highest sensitivity (85%) and, when coupled to LS, highest specificity (83%). CONCLUSIONS: VM could be useful when screening for possible or early autonomic neuropathy, VM + LS is useful as a diagnostic tool for probable or advanced autonomic neuropathy, and VM + LS + PH is useful for certain diagnosis of definite or late stage autonomic neuropathy.


Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades Cardiovasculares/diagnóstico , Sistema Cardiovascular/fisiopatología , Angiopatías Diabéticas/diagnóstico , Neuropatías Diabéticas/diagnóstico , Técnicas de Diagnóstico Cardiovascular , Anciano , Sistema Nervioso Autónomo/fisiopatología , Enfermedades Cardiovasculares/fisiopatología , Angiopatías Diabéticas/fisiopatología , Técnicas de Diagnóstico Endocrino , Femenino , Humanos , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/fisiopatología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Maniobra de Valsalva/fisiología
16.
Clin Neurophysiol ; 130(1): 189-195, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30527385

RESUMEN

OBJECTIVE: Compare activation patterns within the cortical autonomic network in patients with neurogenic orthostatic hypotension (NOH) versus healthy age-matched controls during an orthostatic challenge. METHODS: Fifteen health controls and 15 NOH patients performed 3 Valsalva maneuvers, and 5-min of lower-body negative pressure (LBNP) during a functional brain MRI. RESULTS: Compared to controls, NOH patients had significantly less activation within the cerebellum during both LBNP and VM. Both groups had significant activation of the bilateral insula and left thalamus during LBNP. No significant differences were found during the recovery phase of LBNP. CONCLUSIONS: The cerebellum, which plays an important role in vestibulo-sympathetic reflexes, important for blood pressure adjustments during postural changes, appear to be affected in patients with NOH. The cerebellum also appears to be affected during other baroreflex mediated stressors such as the VM. SIGNIFICANCE: Orthostatic reflexes mediated by the cerebellum may be impaired in patients with NOH. The results suggest an additional pathological pathway in patients with autonomic failure.


Asunto(s)
Barorreflejo/fisiología , Presión Sanguínea/fisiología , Cerebelo/fisiopatología , Hipotensión Ortostática/diagnóstico por imagen , Maniobra de Valsalva/fisiología , Anciano , Cerebelo/diagnóstico por imagen , Femenino , Humanos , Hipotensión Ortostática/fisiopatología , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad
17.
Physiol Rev ; 99(1): 807-851, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30540225

RESUMEN

This review presents lower body negative pressure (LBNP) as a unique tool to investigate the physiology of integrated systemic compensatory responses to altered hemodynamic patterns during conditions of central hypovolemia in humans. An early review published in Physiological Reviews over 40 yr ago (Wolthuis et al. Physiol Rev 54: 566-595, 1974) focused on the use of LBNP as a tool to study effects of central hypovolemia, while more than a decade ago a review appeared that focused on LBNP as a model of hemorrhagic shock (Cooke et al. J Appl Physiol (1985) 96: 1249-1261, 2004). Since then there has been a great deal of new research that has applied LBNP to investigate complex physiological responses to a variety of challenges including orthostasis, hemorrhage, and other important stressors seen in humans such as microgravity encountered during spaceflight. The LBNP stimulus has provided novel insights into the physiology underlying areas such as intolerance to reduced central blood volume, sex differences concerning blood pressure regulation, autonomic dysfunctions, adaptations to exercise training, and effects of space flight. Furthermore, approaching cardiovascular assessment using prediction models for orthostatic capacity in healthy populations, derived from LBNP tolerance protocols, has provided important insights into the mechanisms of orthostatic hypotension and central hypovolemia, especially in some patient populations as well as in healthy subjects. This review also presents a concise discussion of mathematical modeling regarding compensatory responses induced by LBNP. Given the diverse applications of LBNP, it is to be expected that new and innovative applications of LBNP will be developed to explore the complex physiological mechanisms that underline health and disease.


Asunto(s)
Presión Sanguínea/fisiología , Hemodinámica/fisiología , Hipotensión Ortostática/fisiopatología , Hipovolemia/fisiopatología , Presión Negativa de la Región Corporal Inferior , Animales , Humanos , Vuelo Espacial
18.
Hypertension ; 73(1): 235-241, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30571543

RESUMEN

Patients with autonomic failure are characterized by disabling orthostatic hypotension because of impaired sympathetic activity, but even severely affected patients have residual sympathetic tone which can be harnessed for their treatment. For example, norepinephrine transporter blockade with atomoxetine raises blood pressure (BP) in autonomic failure patients by increasing synaptic norepinephrine concentrations; acetylcholinesterase inhibition with pyridostigmine increases BP by facilitating ganglionic cholinergic neurotransmission to increase sympathetic outflow. We tested the hypothesis that pyridostigmine will potentiate the pressor effect of atomoxetine and improve orthostatic tolerance and symptoms in patients with severe autonomic failure. Twelve patients received a single oral dose of either placebo, pyridostigmine 60 mg, atomoxetine 18 mg or the combination on separate days in a single blind, crossover study. BP was assessed seated and standing before and 1-hour postdrug. In these severely affected patients, neither pyridostigmine nor atomoxetine improved BP or orthostatic tolerance compared with placebo. The combination, however, significantly increased seated BP in a synergistic manner (133±9/80±4 versus 107±6/66±4 mm Hg for placebo, 105±5/67±3 mm Hg for atomoxetine, and 99±6/64±4 mm Hg for pyridostigmine; P<0.001); the maximal increase in seated BP with the combination was 33±8/18±3 mm Hg at 60 minutes postdrug. Only the combination showed a significant improvement of orthostatic tolerance and symptoms. In conclusion, the combination pyridostigmine and atomoxetine had a synergistic effect on seated BP which was associated with improvement in orthostatic tolerance and symptoms. This pharmacological approach could be useful in patients with severe autonomic failure but further safety and long-term efficacy studies are needed.


Asunto(s)
Clorhidrato de Atomoxetina , Enfermedades del Sistema Nervioso Autónomo , Presión Sanguínea/efectos de los fármacos , Hipotensión Ortostática , Bromuro de Piridostigmina , Adulto , Clorhidrato de Atomoxetina/administración & dosificación , Clorhidrato de Atomoxetina/farmacocinética , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/tratamiento farmacológico , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Determinación de la Presión Sanguínea/métodos , Estudios Cruzados , Monitoreo de Drogas/métodos , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Femenino , Humanos , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/tratamiento farmacológico , Hipotensión Ortostática/fisiopatología , Masculino , Bromuro de Piridostigmina/administración & dosificación , Bromuro de Piridostigmina/farmacocinética , Método Simple Ciego , Resultado del Tratamiento , Vasoconstrictores/administración & dosificación , Vasoconstrictores/farmacocinética
19.
Am J Physiol Heart Circ Physiol ; 316(3): H734-H742, 2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-30592900

RESUMEN

Peripheral venous distension mechanically stimulates type III/IV sensory fibers in veins and evokes pressor and sympathoexcitatory reflex responses in humans. As young women have reduced venous compliance and impaired sympathetic transduction, we tested the hypothesis that pressor and sympathoexcitatory responses to venous distension may be attenuated in women compared with men. Mean arterial pressure (photoplethysmography), heart rate (HR), stroke volume (SV; Modelflow), cardiac output (CO = HR × SV), muscle sympathetic nerve activity (MSNA), femoral artery blood flow, and femoral artery conductance (Doppler ultrasound) were quantified in eight men (27 ± 4 yr) and nine women (28 ± 4 yr) before [control (CON)], during (INF), and immediately after (post-INF) a local infusion of saline [5% of the total forearm volume (30 ml/min); the infusion time was 2 ± 1 and 1 ± 1 min ( P = 0.0001) for men and women, respectively] through a retrograde catheter inserted into an antecubital vein, to which venous drainage and arterial supply had been occluded. Mean arterial pressure increased during and after infusion in both groups (vs. the CON group, P < 0.05), but women showed a smaller pressor response in the post-INF period (Δ+7.2 ± 2.0 vs. Δ+18.3 ± 3.9 mmHg in men, P = 0.019). MSNA increased and femoral artery conductance decreased similarly in both groups (vs. the CON group, P < 0.05) at post-INF. Although HR changes were similar, increases in SV (Δ+20.4 ± 8.6 vs. Δ+2.6 ± 2.7 ml, P = 0.05) and CO (Δ+0.84 ± 0.17 vs. Δ+0.34 ± 0.10 l/min, P = 0.024) were greater in men compared with women. Therefore, venous distension evokes a smaller pressor response in young women due to attenuated cardiac adjustments rather than reduced venous compliance or sympathetic transduction. NEW & NOTEWORTHY We found that the pressor response to venous distension was attenuated in young women compared with age-matched men. This was due to attenuated cardiac adjustments rather than reduced venous compliance, sympathetic activation, or impaired transduction and vascular control. Collectively, these findings suggest that an attenuated venous distension reflex could be involved in orthostatic intolerance in young women.


Asunto(s)
Hemodinámica/fisiología , Músculo Liso Vascular/fisiología , Sistema Nervioso Simpático/fisiología , Adulto , Presión Arterial/fisiología , Femenino , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/fisiología , Antebrazo/irrigación sanguínea , Humanos , Hipotensión Ortostática/fisiopatología , Masculino , Músculo Liso Vascular/inervación , Estimulación Física , Flujo Sanguíneo Regional/fisiología , Células Receptoras Sensoriales/fisiología , Caracteres Sexuales , Resistencia Vascular , Adulto Joven
20.
Ageing Res Rev ; 48: 122-144, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30394339

RESUMEN

BACKGROUND: Orthostatic hypotension (OH) may negatively affect physical functioning and aggravate morbidities, but existing evidence is contradictory. METHODS: MEDLINE (from 1946), PubMed (from 1966) and EMBASE databases (from 1947) were systematically searched for studies on the association of OH and physical functioning in older adults, categorized as: balance, gait characteristics, walking speed, Timed Up and Go time, handgrip strength (HGS), physical frailty, exercise tolerance, physical activity, activities of daily living (ADL), and performance on the Hoehn and Yahr scale (HY) and Unified Parkinson's Disease Rating Scale (UPDRS). Study quality was assessed using the Newcastle Ottawa Scale. RESULTS: Forty-two studies were included in the systematic review (29,421 individuals) and 29 studies in the meta-analyses (23,879 individuals). Sixteen out of 42 studies reported a significant association of OH with worse physical functioning. Meta-analysis showed a significant association of OH with impaired balance, ADL performance and HY/UPDRS III performance, but not with gait characteristics, mobility, walking speed, TUG, HGS, physical frailty, exercise tolerance, physical activity and UPDRS II performance. CONCLUSIONS: OH was associated with impaired balance, ADL performance and HY/UPDRS III performance, but not with other physical functioning categories. The results suggest that OH interventions could potentially improve some aspects of physical functioning.


Asunto(s)
Envejecimiento/fisiología , Ejercicio/fisiología , Marcha/fisiología , Fuerza de la Mano/fisiología , Hipotensión Ortostática/fisiopatología , Anciano , Envejecimiento/psicología , Estudios Transversales , Ejercicio/psicología , Femenino , Humanos , Hipotensión Ortostática/diagnóstico , Masculino , Estudios Prospectivos , Caminata/fisiología , Caminata/psicología
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