RESUMEN

Importance: Diseases of despair (ie, mortality or morbidity from suicidality, drug abuse, and alcoholism) were first characterized as increasing in rural White working-class populations in midlife with low educational attainment and associated with long-term economic decline. Excess mortality now appears to be associated with working-class citizens across demographic and geographic boundaries, but no known qualitative studies have engaged residents of rural and urban locales with high prevalence of diseases of despair to learn their perspectives. Objective: To explore perceptions about despair-related illness and potential intervention strategies among diverse community members residing in discrete rural and urban hotspots. Design, Setting, and Participants: In this qualitative study, high-prevalence hotspots for diseases of despair were identified from health insurance claims data in Central Pennsylvania. Four focus groups were conducted with 60 community members in organizations and coalitions from 3 census block group hotspot clusters in the health system between September 2019 and January 2020. Focus groups explored awareness and beliefs about causation and potential intervention strategies. Main Outcomes and Measures: A descriptive phenomenological approach was applied to thematic analysis, and a preliminary conceptual model was constructed to describe how various factors may be associated with perpetuating despair and with public health. Results: In total, 60 adult community members participated in 4 focus groups (44 women, 16 men; 40 White non-Hispanic, 17 Black, and 3 Hispanic/Latino members). Three focus groups with 43 members were held in rural areas with high prevalence of diseases of despair, and 1 focus group with 17 members in a high-prevalence urban area. Four themes emerged with respect to awareness and believed causation of despair-related illness, and participants identified common associated factors, including financial distress, lack of critical infrastructure and social services, deteriorating sense of community, and family fragmentation. Intervention strategies focused around 2 themes: (1) building resilience to despair through better community and organizational coordination and peer support at the local level and (2) encouraging broader state investments in social services and infrastructure to mitigate despair-related illness. Conclusions and Relevance: In this qualitative study, rural and urban community members identified common factors associated with diseases of despair, highlighting the association between long-term political and economic decline and public health and a need for both community- and state-level solutions to address despair. Health care systems participating in addressing community health needs may improve processes to screen for despair (eg, social history taking) and codesign primary, secondary, and tertiary interventions aimed at addressing factors associated with distress. Such actions have taken on greater urgency with the COVID-19 pandemic.

Asunto(s)

Alcoholismo/prevención & control , Actitud , Características de la Residencia , Población Rural , Trastornos Relacionados con Sustancias/prevención & control , Prevención del Suicidio , Población Urbana , Adulto , Alcoholismo/etiología , Concienciación , COVID-19 , Atención a la Salud , Familia , Femenino , Grupos Focales , Esperanza , Humanos , Masculino , Persona de Mediana Edad , Grupo Paritario , Investigación Cualitativa , Resiliencia Psicológica , Clase Social , Servicio Social , Trastornos Relacionados con Sustancias/etiología , Suicidio/psicología , Adulto Joven

RESUMEN

BACKGROUND AND OBJECTIVE: Increasing mortality and decreasing life expectancy in the USA are largely attributable to accidental overdose, alcohol-related disease and suicide. These 'deaths of despair' often follow years of morbidity, yet little is known about trends in the clinical recognition of 'diseases of despair'. The objective of this study is to characterise rates of clinically documented diseases of despair over the last decade and identify sociodemographic risk factors. DESIGN: Retrospective study using a healthcare claims database with 10 years of follow-up. SETTING: Participants resided nationwide but were concentrated in US states disproportionately affected by deaths of despair, including Pennsylvania, West Virginia and Delaware. PARTICIPANTS: Cohort included 12 144 252 participants, with no restriction by age or gender. OUTCOME MEASURES: Diseases of despair were defined as diagnoses related to alcohol misuse, substance misuse and suicide ideation/behaviours. A lookback period was used to identify incident diagnoses. Annual and all-time incidence/prevalence estimates were computed, along with risk for current diagnosis and patterns of comorbidity. RESULTS: 515 830 participants received a disease of despair diagnosis (58.5% male, median 36 years). From 2009 to 2018, the prevalence of alcohol-related, substance-related and suicide-related diagnoses respectively increased by 37%, 94%, and 170%. Ages 55-74 had the largest increase in alcohol/substance-related diagnoses (59% and 172%). Ages <18 had the largest increase in suicide-related diagnoses (287%). Overall, odds for current-year diagnosis were higher among men (adjusted OR (AOR) 1.49, 95% CI 1.47 to 1.51), and among those with Affordable Care Act or Medicare coverage relative to commercial coverage (AOR 1.30, 1.24 to 1.37; AOR 1.51, 1.46 to 1.55). CONCLUSIONS: Increasing clinical rates of disease of despair diagnoses largely mirror broader societal trends in mortality. While the opioid crisis remains a top public health priority, parallel rises in alcohol-related diagnoses and suicidality must be concurrently addressed. Findings suggest opportunities for healthcare systems and providers to deploy targeted prevention to mitigate the progression of morbidities towards mortality.

Asunto(s)

Medicare , Patient Protection and Affordable Care Act , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pennsylvania , Estudios Retrospectivos , Estados Unidos/epidemiología

RESUMEN

Patients with heart failure and sleep apnea have greater chemoreflex sensitivity, presumably due to intermittent hypoxia (IH), and this is predictive of mortality. We hypothesized that endurance training would attenuate the effect of IH on peripheral chemoreflex sensitivity in healthy humans. Fifteen young healthy subjects (9 female, 26 ± 1 yr) participated. Between visits, 11 subjects underwent 8 wk of endurance training that included running four times/wk at 80% predicted maximum heart rate and interval training, and four control subjects did not change activity. Chemoreflex sensitivity (the slope of ventilation responses to serial oxygen desaturations), blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) were assessed before and after 30 min of IH. Endurance training decreased resting systolic blood pressure (119 ± 3 to 113 ± 3 mmHg; P = 0.027) and heart rate (67 ± 3 to 61 ± 2 beats/min; P = 0.004) but did not alter respiratory parameters at rest (P > 0.2). Endurance training attenuated the IH-induced increase in chemoreflex sensitivity (pretraining: Δ 0.045 ± 0.026 vs. posttraining: Δ -0.028 ± 0.040 l·min-1·% O2 desaturation-1; P = 0.045). Furthermore, IH increased mean blood pressure and MSNA burst rate before training (P < 0.05), but IH did not alter these measures after training (P > 0.2). All measurements were similar in the control subjects at both visits (P > 0.05). Endurance training attenuates chemoreflex sensitization to IH, which may partially explain the beneficial effects of exercise training in patients with cardiovascular disease.

Asunto(s)

Presión Sanguínea/fisiología , Células Quimiorreceptoras/fisiología , Oxígeno/metabolismo , Acondicionamiento Físico Humano , Resistencia Física/fisiología , Adulto , Anaerobiosis/fisiología , Femenino , Frecuencia Cardíaca/fisiología , Entrenamiento de Intervalos de Alta Intensidad , Humanos , Masculino , Reflejo

RESUMEN

Hyperthyroidism induces marked changes in hemodynamics. Although considerable research has been done to study the effect of hyperthyroidism on the cardiovascular system, few studies have isolated the short-term, nongenomic effects of thyroid hormone on cardiovascular responses to exercise. We used near-infrared spectroscopy to measure muscle oxygenation, Doppler ultrasound to measure skeletal muscle blood flow, and microneurography to measure muscle sympathetic nerve activity (MSNA) during fatiguing dynamic handgrip in twelve healthy males (26 ± 1 years). Subjects were measured separately in both the euthyroid state, and acute hyperthyroid state (approximately ten times the normal levels of T3), induced by oral dosage of 300 µg of triiodothyronine (T3). Forearm blood flow was increased as a function of exercise time in the euthyroid and hyperthyroid state (Δ161.8 ± 45.0 mL/min and Δ140.7 ± 16.3 mL/min, respectively) but there was no significant difference between trials. Forearm vascular conductance (FVC) also increased as a function of exercise time with no significant difference between treatments at submaximal exercise but was significantly less with T3 treatment. MSNA was not different at rest or during submaximal exercise; however, MSNA was significantly greater at fatigue during the hyperthyroid state. Muscle oxyhemoglobin concentration was decreased during exercise in both euthyroid and hyperthyroid states (Δ19.7 ± 10.8% and Δ14.8 ± 9.6%, respectively); whereas deoxyhemoglobin concentration was increased (Δ50.0 ± 4.1% and Δ50.0 ± 6.2%, respectively). These results indicate that T3 had no direct effect on skeletal muscle oxygenation or blood flow during dynamic exercise, but elicited greater MSNA and lower FVC during fatiguing exercise.

RESUMEN

Melatonin attenuates muscle sympathetic nerve responses to sympathoexcitatory stimuli, but it is unknown whether melatonin similarly attenuates reflex changes in skin sympathetic nerve activity (SSNA). In this double-blind, placebo-controlled, crossover study, we tested the hypothesis that melatonin (3 mg) would attenuate the SSNA response to mental stress (mental arithmetic). Twelve healthy subjects underwent experimental testing on two separate days. Three minutes of mental stress occurred before and 45 min after ingestion of melatonin (3 mg) or placebo. Skin temperature was maintained at 34°C. Reflex increases in SSNA (peroneal nerve), mean arterial pressure, and heart rate (HR) to mental stress before and after melatonin were determined. Melatonin lowered HR (pre, 66 ± 3 beats/min; and post, 62 ± 3 beats/min, P = 0.046) and SSNA (pre, 14,282 ± 3,706 arbitrary units; and post, 9,571 ± 2,609 arbitrary units, P = 0.034) at rest. In response to mental stress, SSNA increases were significantly attenuated following melatonin ingestion (second minute, 114 ± 30 vs. 74 ± 14%; and third minute, 111 ± 29 vs. 54 ± 12%, both P < 0.05). The mean arterial pressure increase to mental stress was blunted in the third minute (20 ± 2 vs. 17 ± 2 mmHg, P = 0.032), and the HR increase was blunted in the first minute (33 ± 3 vs. 29 ± 3 beats/min, P = 0.034) after melatonin. In summary, exogenous melatonin attenuates the SSNA response to mental stress.

Asunto(s)

Melatonina/administración & dosificación , Nervio Peroneo/efectos de los fármacos , Reflejo/efectos de los fármacos , Piel/inervación , Estrés Psicológico/fisiopatología , Sistema Nervioso Simpático/efectos de los fármacos , Administración Oral , Adulto , Presión Arterial/efectos de los fármacos , Estudios Cruzados , Método Doble Ciego , Femenino , Voluntarios Sanos , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Conceptos Matemáticos , Pennsylvania , Nervio Peroneo/fisiopatología , Estrés Psicológico/etiología , Sistema Nervioso Simpático/fisiopatología , Factores de Tiempo

RESUMEN

Incidences of adverse cardiac events and orthostatic hypotension are associated with diurnal variations. The primary purpose of the present study was to determine if the vestibulosympathetic reflex (VSR) follows a diurnal variation in humans. We hypothesized that the VSR would be attenuated at night based on the relation between melatonin and the VSR. Arterial blood pressure, heart rate, calf blood flow, and muscle sympathetic nerve activity (MSNA) were measured in nine healthy subjects (28 ± 1 yr, 5 men and 4 women) at rest and during head-down rotation. Each subject was tested during the day at 11:34 ± 13 and again at night 22:10 ± 5. MSNA was significantly decreased at night compared with day (8 ± 1 vs. 11 ± 2 bursts/min, respectively, P < 0.02). Heart rate and arterial blood pressure at rest were significantly increased at night compared with day (heart rate: 70 ± 4 vs. 66 ± 4 beats/min and mean arterial blood pressure: 91 ± 2 vs. 87 ± 1 mmHg, respectively). MSNA and hemodynamic responses to head-down rotation were not significantly altered at night compared with day (changes of 3 ± 1 bursts/min and 25 ± 6% for MSNA and calf blood flow, respectively). The data indicate that MSNA at rest decreases during the late evening hours and exhibits a diurnal variation, whereas the VSR does not. In summary, diurnal variation of orthostatic hypotension in humans does not appear to be associated with changes in the VSR and MSNA at rest.

Asunto(s)

Ritmo Circadiano , Hipotensión Ortostática/fisiopatología , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/inervación , Reflejo , Sistema Nervioso Simpático/fisiopatología , Vestíbulo del Laberinto/inervación , Adulto , Presión Arterial , Femenino , Inclinación de Cabeza , Frecuencia Cardíaca , Humanos , Extremidad Inferior , Masculino , Flujo Sanguíneo Regional , Rotación , Factores de Tiempo

RESUMEN

Mental stress (MS) is a known trigger of myocardial infarction and sudden death. By activating the sympathetic nervous system, MS may have deleterious effect on the cardiovascular system but this process is not completely understood. The primary aim of this study was to quantify the effect of MS on skin sympathetic nerve activity (SSNA). The secondary aim was to determine the reproducibility of SSNA to MS within a given day and ~1 week later. Ten subjects (26±1 yr.) performed two bouts of mental arithmetic lasting 3 min. The bouts were separated by 45 min. One week later the subjects returned to repeat MS. All experiments were conducted in the supine posture during the morning hours. To maintain neutral skin temperature, each subject wore a custom suit (34-35°C). Skin blood flow and sweat rate were measured on the dorsal foot. MS elicited a marked increase in SSNA within the first 10 s (184±42%; P<0.01) in all subjects, which was less during the remaining period of MS but remained elevated (87±20; P<0.01). The pattern of responses to MS was unchanged during the second bout (10 s, 247±55%; 3 min avg., 133±29%) and during the retest 1 week later (10 s, 196±55%; 3 min avg., 117±36%). MS did not significantly affect cutaneous vascular conductance or sweat rate during any trial. In summary, MS elicits robust and reproducible increases in SSNA in humans which may be followed over time to observe alterations in the regulation of the autonomic nervous system.

Asunto(s)

Barorreflejo/fisiología , Fenómenos Fisiológicos Cardiovasculares , Postura/fisiología , Reflejo/fisiología , Vestíbulo del Laberinto/fisiología , Animales , Masculino

RESUMEN

The mechanism(s) for post-bed rest (BR) orthostatic intolerance is equivocal. The vestibulosympathetic reflex contributes to postural blood pressure regulation. It was hypothesized that muscle sympathetic nerve responses to otolith stimulation would be attenuated by prolonged head-down BR. Arterial blood pressure, heart rate, muscle sympathetic nerve activity (MSNA), and peripheral vascular conductance were measured during head-down rotation (HDR; otolith organ stimulation) in the prone posture before and after short-duration (24 h; n = 22) and prolonged (36 ± 1 day; n = 8) BR. Head-up tilt at 80° was performed to assess orthostatic tolerance. After short-duration BR, MSNA responses to HDR were preserved (Δ5 ± 1 bursts/min, Δ53 ± 13% burst frequency, Δ65 ± 13% total activity; P < 0.001). After prolonged BR, MSNA responses to HDR were attenuated ∼50%. MSNA increased by Δ8 ± 2 vs. Δ3 ± 2 bursts/min and Δ83 ± 12 vs. Δ34 ± 22% total activity during HDR before and after prolonged BR, respectively. Moreover, these results were observed in three subjects tested again after 75 ± 1 days of BR. This reduction in MSNA responses to otolith organ stimulation at 5 wk occurred with reductions in head-up tilt duration. These results indicate that prolonged BR (∼5 wk) unlike short-term BR (24 h) attenuates the vestibulosympathetic reflex and possibly contributes to orthostatic intolerance following BR in humans. These results suggest a novel mechanism in the development of orthostatic intolerance in humans.

Asunto(s)

Reposo en Cama/efectos adversos , Músculo Esquelético/inervación , Intolerancia Ortostática/etiología , Reflejo , Sistema Nervioso Simpático/fisiopatología , Vestíbulo del Laberinto/inervación , Adulto , Análisis de Varianza , Presión Sanguínea , Femenino , Inclinación de Cabeza , Frecuencia Cardíaca , Humanos , Masculino , Músculo Esquelético/irrigación sanguínea , Intolerancia Ortostática/fisiopatología , Pennsylvania , Flujo Sanguíneo Regional , Rotación , Factores de Tiempo , Adulto Joven

RESUMEN

The glycerol dehydration test (GDT) has been used to test for the presence of Ménière's disease and elicits acute alterations in vestibular reflexes in both normal and pathological states. Activation of the vestibulosympathetic reflex (VSR) increases muscle sympathetic nerve activity (MSNA) and peripheral vascular resistance. We hypothesized that the GDT would attenuate the VSR through fluid shifts of the inner ear. Sixteen male subjects (26 ± 1 yr) were randomly assigned to be administered either glycerol mixed with cranberry juice (97 ± 3 ml glycerol + equal portion of cranberry juice; n = 9) or a placebo control [water + cranberry juice (100 ml each); n = 7]. Subjects in both groups performed head-down rotation (HDR), which engages the VSR, before and after administration of either the glycerol or placebo. MSNA (microneurography), arterial blood pressure, and leg blood flow (venous occlusion plethysmography) were measured during HDR. Before glycerol administration, HDR significantly increased MSNA burst frequency (Δ8 ± 1 bursts/min; P < 0.01) and total activity (Δ77 ± 18%; P < 0.01) and decreased calf vascular conductance (-Δ20 ± 3%; P < 0.01). However, HDR performed postadministration of glycerol resulted in an attenuated MSNA increase (Δ3 ± 1 bursts/min, Δ22 ± 3% total activity) and decrease in calf vascular conductance (-Δ7 ± 4%). HDR significantly increased MSNA burst frequency (Δ5 ± 1 and Δ5 ± 2 bursts/min) and total activity (Δ58 ± 13% and Δ52 ± 18%) in the placebo group before and after placebo, respectively (P < 0.01). Likewise, decreases in calf vascular conductance during HDR before and after placebo were not different (-Δ13 ± 4% and -Δ14 ± 2%, respectively; P < 0.01). These results suggest that fluid shifts of the inner ear via glycerol dehydration attenuate the VSR. These data provide support that inner ear fluid dynamics can have a significant impact on blood pressure regulation via the VSR in humans.

Asunto(s)

Deshidratación/fisiopatología , Transferencias de Fluidos Corporales , Glicerol/administración & dosificación , Hemodinámica , Extremidad Inferior/irrigación sanguínea , Reflejo , Sistema Nervioso Simpático/fisiopatología , Vestíbulo del Laberinto/inervación , Administración Oral , Adulto , Presión Sanguínea , Deshidratación/inducido químicamente , Frecuencia Cardíaca , Humanos , Masculino , Flujo Sanguíneo Regional , Factores de Tiempo , Vasoconstricción

RESUMEN

Melatonin is synthesized and released into the circulation by the pineal gland in a circadian rhythm. Melatonin has been demonstrated to differentially alter blood flow to assorted vascular beds by the activation of different melatonin receptors in animal models. The purpose of the present study was to determine the effect of melatonin on blood flow to various vascular beds in humans. Renal (Doppler ultrasound), forearm (venous occlusion plethysmography), and cerebral blood flow (transcranial Doppler), arterial blood pressure, and heart rate were measured in 10 healthy subjects (29±1 yr; 5 men and 5 women) in the supine position for 3 min. The protocol began 45 min after the ingestion of either melatonin (3 mg) or placebo (sucrose). Subjects returned at least 2 days later at the same time of day to repeat the trial after ingesting the other substance. Melatonin did not alter heart rate and mean arterial pressure. Renal blood flow velocity (RBFV) and renal vascular conductance (RVC) were lower during the melatonin trial compared with placebo (RBFV, 40.5±2.9 vs. 45.4±1.5 cm/s; and RVC, 0.47±0.02 vs. 0.54±0.01 cm·s(-1)·mmHg(-1), respectively). In contrast, forearm blood flow (FBF) and forearm vascular conductance (FVC) were greater with melatonin compared with placebo (FBF, 2.4±0.2 vs. 1.9±0.1 ml·100 ml(-1)·min(-1); and FVC, 0.029±0.003 vs. 0.023±0.002 arbitrary units, respectively). Melatonin did not alter cerebral blood flow measurements compared with placebo. Additionally, phentolamine (5-mg bolus) after melatonin reversed the decrease in RVC, suggesting that melatonin increases sympathetic outflow to the kidney to mediate renal vasoconstriction. In summary, exogenous melatonin differentially alters vascular blood flow in humans. These data suggest the complex nature of melatonin on the vasculature in humans.

Asunto(s)

Antebrazo/irrigación sanguínea , Melatonina/farmacología , Flujo Sanguíneo Regional/efectos de los fármacos , Antagonistas Adrenérgicos alfa/farmacología , Adulto , Presión Sanguínea/efectos de los fármacos , Circulación Cerebrovascular/efectos de los fármacos , Método Doble Ciego , Ecocardiografía Doppler , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Fentolamina/farmacología , Pletismografía , Circulación Renal/efectos de los fármacos , Ultrasonografía Doppler Transcraneal

Asunto(s)

Acetilcolina/administración & dosificación , Fibras Colinérgicas/fisiología , Ejercicio Físico/fisiología , Glándulas Sudoríparas/inervación , Glándulas Sudoríparas/fisiología , Adulto , Colinérgicos/administración & dosificación , Fibras Colinérgicas/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Consumo de Oxígeno/fisiología

RESUMEN

Endurance training has been associated with increased orthostatic intolerance. The purpose of the present study was to test the hypothesis that endurance training reduces renal vasoconstriction to orthostatic stress. Blood pressure, heart rate, and renal blood flow velocity were measured during a 25-min 60 degrees head-up tilt (HUT) test before and after 8 wk of endurance training in eight healthy sedentary subjects (26 +/- 1 yrs). Training elicited a 21 +/- 3% increase in peak oxygen uptake (V(O(2)peak)) and a reduction in heart rate at rest of 8 +/- 2 beats/min. During HUT, heart rate progressively increased (approximately 20 beats/min) over the 25-min HUT trial both before and after training. Systolic arterial blood pressure during HUT was unchanged with training, whereas diastolic arterial blood pressure was lower at the end of HUT after training. Before training renal blood flow velocity (Delta14 +/- 5 cm/s) and renal vascular conductance (Delta22 +/- 7%) decreased during HUT, whereas after training renal blood flow velocity (Delta2 +/- 5 cm/s) and renal vascular conductance (Delta1 +/- 12%) did not change significantly during HUT. Renal blood flow velocity and vascular conductance responses to HUT did not change in control subjects during the 8-wk period. These results demonstrate that endurance training reduces renal vasoconstriction during an orthostatic challenge and may contribute to training-induced orthostatic intolerance.

Asunto(s)

Riñón/irrigación sanguínea , Intolerancia Ortostática/fisiopatología , Educación y Entrenamiento Físico , Resistencia Física , Vasoconstricción , Adulto , Ciclismo , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Consumo de Oxígeno , Carrera , Pruebas de Mesa Inclinada

RESUMEN

Cardiovascular-related mortality peaks during cold winter months, particularly in older adults. Acute physiological responses, such as increases in blood pressure, in response to cold exposure may contribute to these associations. To determine whether the blood pressure-raising effect (pressor response) of non-internal body temperature-reducing cold stress is greater with age, we measured physiological responses to 20 min of superficial skin cooling, via water-perfused suit, in 12 younger [25 +/- 1 (SE) yr old] and 12 older (65 +/- 2 yr old) adults. We found that superficial skin cooling elicited an increase in blood pressure from resting levels (pressor response; P < 0.05) in younger and older adults. However, the magnitude of this pressor response (systolic and mean blood pressure) was more than twofold higher in older adults (P < 0.05 vs. younger adults). The magnitude of the pressor response was similar at peripheral (brachial) and central (estimated in the aorta) measurement sites. Regression analysis revealed that aortic pulse wave velocity, a measure of central arterial stiffness obtained before cooling, was the best predictor of the increased pressor response to superficial skin cooling in older adults, explaining approximately 63% of its variability. These results indicate that there is a greater pressor response to non-internal body temperature-reducing cold stress with age in humans that may be mediated by increased levels of central arterial stiffness.

Asunto(s)

Envejecimiento , Aorta/fisiología , Frío , Hemodinámica , Temperatura Cutánea , Estrés Fisiológico , Adulto , Factores de Edad , Anciano , Aorta/diagnóstico por imagen , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Elasticidad , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Manometría , Persona de Mediana Edad , Flujo Pulsátil , Flujo Sanguíneo Regional , Factores de Tiempo , Ultrasonografía Doppler , Adulto Joven

RESUMEN

The purpose of the study was to determine the interactive effect of aging and forearm muscle heating on renal vascular conductance and muscle sympathetic nerve activity (MSNA) during ischemic isometric handgrip. A tube-lined, water-perfused sleeve was used to heat the forearm in 12 young (27 +/- 1 yr) and 9 older (63 +/- 1 yr) subjects. Ischemic isometric handgrip was performed before and after heating. Muscle temperature (intramuscular thermistor) was 34.3 +/- 0.2 and 38.7 +/- 0.1 degrees C during normothermia and heating, respectively. At rest, heating had no effect on renal blood velocity (Doppler ultrasound) or renal vascular conductance in either group (young, n = 12; older, n = 8). Heating compared with normothermia caused a significantly greater increase in renal vasoconstriction during exercise and postexercise muscle ischemia (PEMI) in both groups. However, the increase in renal vasoconstriction during heating was greater in the older compared with the young subjects (18 +/- 3 vs. 8 +/- 3%). During handgrip, heating elicited greater increases in MSNA responses in the older group (young, n = 12; older, n = 6), whereas no statistical difference was observed between groups during PEMI. In summary, aging augments renal vascular responses to ischemic isometric handgrip during heating of the exercising muscle. The greater renal vasoconstriction was associated with augmented MSNA in the older subjects.

Asunto(s)

Envejecimiento , Fuerza de la Mano , Hipotermia Inducida , Isquemia/fisiopatología , Contracción Isométrica , Músculo Esquelético/fisiopatología , Arteria Renal/fisiopatología , Circulación Renal , Vasoconstricción , Adulto , Factores de Edad , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Temperatura Corporal , Femenino , Antebrazo , Frecuencia Cardíaca , Humanos , Isquemia/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/inervación , Percepción , Nervio Peroneo/fisiopatología , Esfuerzo Físico , Arteria Renal/diagnóstico por imagen , Sistema Nervioso Simpático/fisiopatología , Factores de Tiempo , Ultrasonografía Doppler

RESUMEN

Engagement of the otolith organs elicits differential activation of sympathetic nerve activity and vascular responses to muscle and skin in humans. Additionally, aging attenuates the otolith organ-mediated increases in muscle sympathetic nerve activity in older adults. In this study, we hypothesized that 1) the vestibulosympathetic reflex (VSR) would elicit visceral vascular vasoconstriction and 2) visceral vascular response to the VSR would be attenuated in older subjects compared with young. To test these hypotheses, heart rate, mean arterial blood pressure, and renal, celiac trunk, and superior mesenteric arterial blood velocity (Doppler ultrasound) were measured in 22 young (25+/-1 yr) and 18 older (65+/-2 yr) healthy subjects during head-down rotation (HDR), which selectively activates the otolith organs. Mean arterial pressure and heart rate did not change from baseline during HDR in young or older subjects. Renal blood velocity (Delta -2+/-1 cm/s) and vascular conductance (Delta -0.03+/-0.01 cm.s(-1).mmHg(-1)) significantly decreased from baseline during HDR (P<0.05) in young subjects. In contrast, renal blood velocity and conductance did not change in older subjects (Delta -0.2+/-1 cm/s and Delta0.02+/-0.08 mmHg.cm(-1).s(-1), respectively) during HDR. Superior mesenteric and celiac blood velocity and vascular conductance did not change in response to HDR in either the young or older subjects. These data suggest that renal vasoconstriction occurs during otolith organ activation in young but not older humans. Together with our previous studies, we conclude that the VSR elicits a diverse patterning of sympathetic outflow that results in heterogeneous vascular responses in humans and that these responses are significantly attenuated in older humans.

Asunto(s)

Envejecimiento/fisiología , Membrana Otolítica/fisiología , Flujo Sanguíneo Regional/fisiología , Arteria Renal/inervación , Sistema Nervioso Simpático/fisiología , Vasoconstricción/fisiología , Adulto , Anciano , Arteria Celíaca/inervación , Arteria Celíaca/fisiología , Femenino , Humanos , Riñón/irrigación sanguínea , Masculino , Arteria Mesentérica Superior/inervación , Arteria Mesentérica Superior/fisiología , Persona de Mediana Edad , Reflejo/fisiología , Arteria Renal/fisiología , Vestíbulo del Laberinto/fisiología , Vísceras/irrigación sanguínea

RESUMEN

Otolith organs have been shown to activate the sympathetic nervous system in the prone position by head-down rotation (HDR) in humans. To date, otolithic stimulation by HDR has not been comprehensively studied in the upright posture. The purpose of the present study was to determine whether otolithic stimulation increases muscle sympathetic nerve activity (MSNA) in the upright posture. It was hypothesized that stimulation of the otolith organs would increase MSNA in the upright posture, despite increased baseline sympathetic activation due to unloading of the baroreceptors. MSNA, arterial blood pressure, heart rate, and degree of head rotation were measured during HDR in 18 volunteers (23 +/- 1 yr) in different postures. Study 1 (n = 11) examined HDR in the prone and sitting positions and study 2 (n = 7) examined HDR in the prone and 60 degrees head-up tilt positions. Baseline MSNA was 8 +/- 4, 15 +/- 4, and 33 +/- 2 bursts/min for prone, sitting, and head-up tilt, respectively. HDR significantly increased MSNA in the prone (Delta4 +/- 1 and Delta105 +/- 37% for burst frequency and total activity, respectively), sitting (Delta5 +/- 1 and Delta43 +/- 12%), and head-up tilt (Delta7 +/- 1 and Delta110 +/- 41%; P < 0.05). Sensitivity of the vestibulosympathetic reflex (%DeltaMSNA/DeltaHDR; degree of head rotation) was significantly greater in the sitting and head-up tilt than prone position (prone = 74 +/- 22; sitting = 109 +/- 30; head-up tilt = 276 +/- 103; P < 0.05). These data indicate that stimulation of the otolith organs can mediate increases in MSNA in the upright posture and suggest a greater sensitivity of the vestibulosympathetic reflex in the upright posture in humans.

Asunto(s)

Postura/fisiología , Reflejo/fisiología , Sistema Nervioso Simpático/fisiología , Vestíbulo del Laberinto/fisiología , Adulto , Presión Sanguínea/fisiología , Femenino , Inclinación de Cabeza , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Fibras Musculares Esqueléticas/fisiología , Músculo Esquelético/inervación , Músculo Esquelético/fisiología , Membrana Otolítica/fisiología , Posición Prona/fisiología , Mecánica Respiratoria/fisiología

RESUMEN

The purpose of this study was to determine neurovascular responses to mental stress (MS) in the supine and upright postures. MS was elicited in 23 subjects (26 +/- 1 yr) by 5 min of mental arithmetic. In study 1 (n = 9), Doppler ultrasound was used to measure mean blood flow velocity in the renal (RBFV) and superior mesenteric arteries (SMBFV), and venous occlusion plethysmography was used to measure forearm blood flow (FBF). In study 2 (n = 14), leg blood flow (LBF; n = 9) was measured by Doppler ultrasound, and muscle sympathetic nerve activity (MSNA; n = 5) was measured by microneurography. At rest, upright posture increased heart rate and MSNA and decreased LBF, FBF, RBFV, and SMBFV and their respective conductances. MS elicited similar increases in mean arterial blood pressure ( approximately 12 mmHg) and heart rate ( approximately 17 beats/min), regardless of posture. MS in both postures elicited a decrease in RBFV, SMBFV, and their conductances and an increase in LBF, FBF, and their conductances. Changes in blood flow were blunted in the upright posture in all vascular beds examined, but the pattern of the vascular response was the same as the supine posture. MS did not change MSNA in either posture (change: approximately 1 +/- 3 and approximately 3 +/- 3 bursts/min, respectively). In conclusion, the augmented sympathetic activity of the upright posture does not alter heart rate, mean arterial blood pressure, or MSNA responses to MS. MS elicits divergent vascular responses in the visceral and peripheral vasculature. These results indicate that, although the upright posture attenuates vascular responses to MS, the pattern of neurovascular responses does not differ between postures.

Asunto(s)

Postura/fisiología , Estrés Psicológico/fisiopatología , Posición Supina/fisiología , Sistema Nervioso Simpático/fisiopatología , Adulto , Presión Sanguínea/fisiología , Femenino , Antebrazo/irrigación sanguínea , Frecuencia Cardíaca/fisiología , Humanos , Pierna/irrigación sanguínea , Masculino , Arteria Mesentérica Superior/fisiología , Flujo Sanguíneo Regional/fisiología , Arteria Renal/fisiología , Ultrasonografía Doppler Dúplex , Resistencia Vascular/fisiología

RESUMEN

The purpose of the present study was to examine the effect of heating and cooling the forearm muscles on renal vascular responses to ischemic isometric handgrip (IHG). It was hypothesized that heating and cooling the forearm would augment and attenuate, respectively, renal vascular responses to IHG. Renal vascular responses to IHG were studied during forearm heating at 39 degrees C (n = 15, 26 +/- 1 yr) and cooling at 26 degrees C (n = 12, 26 +/- 1 yr). For a control trial, subjects performed the experimental protocol while the forearm was normothermic (approximately 34 degrees C). Muscle temperature (measured by intramuscular probe) was controlled by changing the temperature of water cycling through a water-perfused sleeve. The experimental protocol was as follows: 3 min at baseline, 1 min of ischemia, ischemic IHG to fatigue, and 2 min of postexercise muscle ischemia. At rest, renal artery blood velocity (RBV; Doppler ultrasound) and renal vascular conductance (RVC = RBV/mean arterial blood pressure) were not different between normothermia and the two thermal conditions. During ischemic IHG, there were greater decreases in RBV and RVC in the heating trial. However, RBV and RVC were similar during postexercise muscle ischemia during heating and normothermia. RVC decreased less during cooling than in normothermia while the subjects performed the ischemic IHG protocol. During postexercise muscle ischemia, RVC was greater during cooling than in normothermia. These results indicate that heating augments mechanoreceptor-mediated renal vasoconstriction whereas cooling blunts metaboreceptor-mediated renal vasoconstriction.

Asunto(s)

Temperatura Corporal , Ejercicio Físico , Fuerza de la Mano , Isquemia/fisiopatología , Contracción Isométrica , Músculo Esquelético/fisiopatología , Circulación Renal , Sistema Nervioso Simpático/fisiopatología , Vasoconstricción , Adulto , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Frío , Femenino , Antebrazo , Calor , Humanos , Isquemia/diagnóstico por imagen , Isquemia/metabolismo , Masculino , Mecanotransducción Celular , Fatiga Muscular , Husos Musculares/metabolismo , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/inervación , Músculo Esquelético/metabolismo , Reflejo , Arteria Renal/inervación , Arteria Renal/fisiopatología , Sistema Nervioso Simpático/metabolismo , Factores de Tiempo , Ultrasonografía

RESUMEN

Skin-surface cooling elicits a pronounced systemic pressor response, which has previously been reported to be associated with peripheral vasoconstriction and may not fully account for the decrease in systemic vascular conductance. To test the hypothesis that whole body skin-surface cooling would also induce renal and splanchnic vasoconstriction, 14 supine subjects performed 26 skin-surface cooling trials (15-18 degrees C water perfused through a tube-lined suit for 20 min). Oral and mean skin temperature, heart rate, stroke volume (Doppler ultrasound), mean arterial blood pressure (MAP), cutaneous blood velocity (laser-Doppler), and mean blood velocity of the brachial, celiac, renal, and superior mesenteric arteries (Doppler ultrasound) were measured during normothermia and skin-surface cooling. Cardiac output (heart rate x stroke volume) and indexes of vascular conductance (flux or blood velocity/MAP) were calculated. Skin-surface cooling increased MAP (n = 26; 78 +/- 5 to 88 +/- 5 mmHg; mean +/- SD) and decreased mean skin temperature (n = 26; 33.7 +/- 0.7 to 27.5 +/- 1.2 degrees C) and cutaneous (n = 12; 0.93 +/- 0.68 to 0.36 +/- 0.20 flux/mmHg), brachial (n = 10; 32 +/- 15 to 20 +/- 12), celiac (n = 8; 85 +/- 22 to 73 +/- 22 cm.s(-1).mmHg(-1)), superior mesenteric (n = 8; 55 +/- 16 to 48 +/- 10 cm.s(-1).mmHg(-1)), and renal (n = 8; 74 +/- 26 to 64 +/- 20 cm.s(-1).mmHg(-1); all P < 0.05) vascular conductance, without altering oral temperature, cardiac output, heart rate, or stroke volume. These data identify decreases in vascular conductance of skin and of brachial, celiac, superior mesenteric, and renal arteries. Thus it appears that vasoconstriction in both peripheral and visceral arteries contributes importantly to the pressor response produced during skin-surface cooling in humans.

Asunto(s)

Regulación de la Temperatura Corporal/fisiología , Frío , Temperatura Cutánea/fisiología , Piel/irrigación sanguínea , Circulación Esplácnica/fisiología , Vasoconstricción/fisiología , Adulto , Femenino , Hemodinámica/fisiología , Humanos , Masculino , Flujo Sanguíneo Regional/fisiología , Resistencia Vascular