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1.
Physiol Rep ; 12(7): e15998, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38570312

RESUMEN

Chronic kidney disease (CKD) is characterized by an elevated risk for cerebrovascular disease including stroke. One mechanism that may contribute to this heightened risk is an impairment in cerebrovascular carbon dioxide reactivity (CVR). We compared CVR between CKD patients stages III-IV and controls (CON) without CKD but matched for hypertension and diabetes status. CVR was measured via 5% CO2 inhalation followed by voluntary hyperventilation in 14 CKD and 11 CON participants while mean arterial pressure, end-tidal carbon dioxide, and middle cerebral artery blood velocity (MCAv) were measured continuously. CVR was quantified as the linear relationship between etCO2 and MCAv. We observed no difference in CVR between groups. Hypercapnic CVR: CKD = 1.2 ± 0.9 cm/s/mm Hg, CON = 1.3 ± 0.8 cm/s/mm Hg, hypocapnic CVR: CKD = 1.3 ± 0.9 cm/s/mm Hg, CON = 1.5 ± 0.7 cm/s/mm Hg, integrated CVR: CKD = 1.5 ± 1.1 cm/s/mm Hg, CON = 1.7 ± 0.8 cm/s/mm Hg, p ≥ 0.48. Unexpectedly, CVR was inversely related to estimated glomerular filtration rate in CKD (R2 = 0.37, p = 0.02). We report that CVR remains intact in CKD and is inversely related to eGFR. These findings suggest that other mechanisms beyond CVR contribute to the elevated stroke risk observed in CKD.


Asunto(s)
Insuficiencia Renal Crónica , Accidente Cerebrovascular , Humanos , Dióxido de Carbono , Velocidad del Flujo Sanguíneo , Circulación Cerebrovascular
2.
Microvasc Res ; 151: 104624, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37926135

RESUMEN

Vascular impairment is closely related to increased mortality in chronic kidney disease (CKD). The objective of this study was to assess impairments in the regulation of peripheral microvascular perfusion in patients with CKD based on time-frequency spectral analysis of resting near-infrared spectroscopy (NIRS) signals. Total hemoglobin (tHb) concentration and tissue saturation index (TSI) signals were collected using NIRS for a continuous 5 mins at 10 Hz from the forearm of 55 participants (34 CKD including 5 with end-stage renal disease, and 21 age-matched control). Continuous wavelet transform-based spectral analysis was used to quantify the spectral amplitude within five pre-defined frequency intervals (I, 0.0095-0.021 Hz; II, 0.021-0.052 Hz; III, 0.052-0.145 Hz; IV, 0.145-0.6 Hz and V, 0.6-2.0 Hz), representing endothelial, neurogenic, myogenic, respiratory and heartbeat activity, respectively. CKD patients showed lower tHb average spectral amplitude within the neurogenic frequency interval compared with controls (p = 0.014), consistent with an increased sympathetic outflow observed in CKD. CKD patients also showed lower TSI average spectral amplitude within the endothelial frequency interval compared with controls (p = 0.046), consistent with a reduced endothelial function in CKD. These findings demonstrate the potential of wavelet analysis of NIRS to provide complementary information on peripheral microvascular regulation in CKD.


Asunto(s)
Fallo Renal Crónico , Análisis de Ondículas , Humanos , Espectroscopía Infrarroja Corta , Microcirculación
3.
Am J Physiol Heart Circ Physiol ; 324(6): H843-H855, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37000610

RESUMEN

Chronic kidney disease (CKD) is characterized by pronounced exercise intolerance and exaggerated blood pressure reactivity during exercise. Classic mechanisms of exercise intolerance in CKD have been extensively described previously and include uremic myopathy, chronic inflammation, malnutrition, and anemia. We contend that these classic mechanisms only partially explain the exercise intolerance experienced in CKD and that alterations in cardiovascular and autonomic regulation also play a key contributing role. The purpose of this review is to examine the physiological factors that contribute to neurocirculatory dysregulation during exercise and discuss the adaptations that result from regular exercise training in CKD. Key neurocirculatory mechanisms contributing to exercise intolerance in CKD include augmentation of the exercise pressor reflex, aberrations in neurocirculatory control, and increased neurovascular transduction. In addition, we highlight how some contributing factors may be improved through exercise training, with a specific focus on the sympathetic nervous system. Important areas for future work include understanding how the exercise prescription may best be optimized in CKD and how the beneficial effects of exercise training may extend to the brain.


Asunto(s)
Sistema Cardiovascular , Insuficiencia Renal Crónica , Humanos , Músculo Esquelético , Insuficiencia Renal Crónica/terapia , Ejercicio Físico/fisiología , Presión Sanguínea , Sistema Nervioso Simpático
4.
JCI Insight ; 8(4)2023 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-36810250

RESUMEN

BACKGROUNDChronic kidney disease (CKD) is characterized by chronic overactivation of the sympathetic nervous system (SNS), which increases the risk of cardiovascular (CV) disease and mortality. SNS overactivity increases CV risk by multiple mechanisms, including vascular stiffness. We tested the hypothesis that aerobic exercise training would reduce resting SNS activity and vascular stiffness in patients with CKD.METHODSIn this randomized controlled trial, sedentary older adults with CKD underwent 12 weeks of exercise (cycling, n = 32) or stretching (an active control group, n = 26). Exercise and stretching interventions were performed 20-45 minutes/session at 3 days/week and were matched for duration. Primary endpoints include resting muscle sympathetic nerve activity (MSNA) via microneurography, arterial stiffness by central pulse wave velocity (PWV), and aortic wave reflection by augmentation index (AIx).RESULTSThere was a significant group × time interaction in MSNA and AIx with no change in the exercise group but with an increase in the stretching group after 12 weeks. The magnitude of change in MSNA was inversely associated with baseline MSNA in the exercise group. There was no change in PWV in either group over the study period.CONCLUSIONOur data demonstrate that 12 weeks of cycling exercise has beneficial neurovascular effects in patients with CKD. Specifically, exercise training safely and effectively ameliorated the increase in MSNA and AIx observed over time in the control group. This sympathoinhibitory effect of exercise training showed greater magnitude in patients with CKD with higher resting MSNA.TRIAL REGISTRATIONClinicalTrials.gov, NCT02947750.FUNDINGNIH R01HL135183; NIH R61AT10457; NIH NCATS KL2TR002381; and NIH T32 DK00756; NIH F32HL147547; and VA Merit I01CX001065.


Asunto(s)
Enfermedades Cardiovasculares , Insuficiencia Renal Crónica , Rigidez Vascular , Humanos , Anciano , Análisis de la Onda del Pulso , Ejercicio Físico/fisiología , Insuficiencia Renal Crónica/complicaciones , Rigidez Vascular/fisiología
5.
Physiol Rep ; 10(21): e15495, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36325592

RESUMEN

Chronic Kidney Disease (CKD) patients experience an elevated risk for cerebrovascular disease. One factor that may contribute to this heightened risk is an impairment in dynamic cerebral autoregulation, the mechanism by which cerebral vessels modulate cerebral blood flow during fluctuations in arterial pressure. We hypothesized that dynamic cerebral autoregulation would be impaired in CKD. To test this hypothesis, we compared dynamic cerebral autoregulation between CKD patients stages III-IV and matched controls (CON) without CKD. Fifteen patients with CKD and 20 CON participants performed 2, 5-minute bouts of repeated sit-to-stand maneuvers at 0.05 Hz and 0.10 Hz while mean arterial pressure (MAP, via finger photoplethysmography) and middle cerebral artery blood velocity (MCAv, via transcranial Doppler ultrasound) were measured continuously. Cerebral autoregulation was characterized by performing a transfer function analysis (TFA) on the MAP-MCAv relationship to derive coherence, phase, gain, and normalized gain (nGain). We observed no group differences in any of the TFA metrics during the repeated sit-to-stand maneuvers. During the 0.05 Hz maneuver, Coherence: CKD = 0.83 ± 0.13, CON = 0.85 ± 0.12, Phase (radians): CKD = 1.39 ± 0.41, CON = 1.25 ± 0.30, Gain (cm/s/mmHg): CKD = 0.69 ± 0.20, CON = 0.71 ± 0.22, nGain (%/mmHg): CKD = 1.26 ± 0.35, CON = 1.20 ± 0.28, p ≥ 0.24. During the 0.10 Hz maneuver (N = 6 CKD and N = 12 CON), Coherence: CKD = 0.61 ± 0.10, CON = 0.67 ± 0.11, Phase (radians): CKD = 1.43 ± 0.26, CON = 1.30 ± 0.23, Gain (cm/s/mmHg): CKD = 0.75 ± 0.15, CON = 0.84 ± 0.26, nGain (%/mmHg): CKD = 1.50 ± 0.28, CON = 1.29 ± 0.24, p ≥ 0.12. Contrary to our hypothesis, dynamic cerebral autoregulation remains intact in CKD stages III-IV. These findings suggest that other mechanisms likely contribute to the increased cerebrovascular disease burden experienced by this population. Future work should determine if other cerebrovascular regulatory mechanisms are impaired and related to cerebrovascular disease risk in CKD.


Asunto(s)
Circulación Cerebrovascular , Insuficiencia Renal Crónica , Humanos , Velocidad del Flujo Sanguíneo/fisiología , Homeostasis/fisiología , Circulación Cerebrovascular/fisiología , Ultrasonografía Doppler Transcraneal , Arteria Cerebral Media/fisiología , Presión Sanguínea/fisiología
6.
Auton Neurosci ; 241: 103007, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35716525

RESUMEN

A reciprocal relationship between the baroreflex and cerebral autoregulation (CA) has been demonstrated at rest and in response to acute hypotension. We hypothesized that the reciprocal relationship between cardiac baroreflex sensitivity (BRS) and CA would be maintained during sustained central hypovolemia induced by lower body negative pressure (LBNP), and that the strength of this relationship would be greater in subjects with higher tolerance to this stress. Healthy young adults (n = 51; 23F/28M) completed a LBNP protocol to presyncope. Subjects were classified as high tolerant (HT; completion of -60 mmHg LBNP stage, ≥20-min) or low tolerant (LT; did not complete -60 mmHg LBNP stage, <20-min). R-R intervals (RRI), systolic arterial pressure (SAP), mean arterial pressure (MAP), and middle cerebral artery velocity (MCAv) were measured continuously. Cardiac BRS was calculated in the time domain (ΔHR/ΔSAP) and frequency domain (RRI-SAP low frequency (LF) transfer function gain), and CA was calculated in the time domain (ΔMCAv/ΔMAP) and frequency domain (MAP-mean MCAv LF transfer function gain). There was a moderate relationship between cardiac BRS and CA for the group of 51 subjects in both the time (R = -0.54, P < 0.0001) and frequency (R = 0.61, P < 0.001) domains; there was a stronger relationship in the HT group (R = 0.73) compared to the LT group (R = 0.31) in the frequency domain (P = 0.08), but no difference between groups in the time domain (HT: R = -0.73 vs. LT: R = -0.63; P = 0.27). These findings suggest that an interaction between BRS and CA may be an important compensatory mechanism that contributes to tolerance to simulated hemorrhage in young healthy adults.


Asunto(s)
Presión Negativa de la Región Corporal Inferior , Presorreceptores , Presión Sanguínea/fisiología , Frecuencia Cardíaca/fisiología , Hemorragia , Homeostasis/fisiología , Humanos , Adulto Joven
7.
J Appl Physiol (1985) ; 132(3): 785-793, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35142559

RESUMEN

Patients with chronic kidney disease (CKD) have exaggerated increases in blood pressure during exercise that are associated with endothelial dysfunction. We hypothesized that aerobic exercise training would improve endothelial function and attenuate blood pressure reactivity during exercise in CKD. Sedentary individuals with CKD stages III-IV underwent 12 wk of aerobic cycling exercise (n = 26) or nonaerobic exercise (n = 22, control). Both interventions were performed 3 days/wk and matched for duration. Endothelial function was measured via peripheral arterial tonometry and quantified as reactive hyperemia index (RHI). Peak oxygen uptake (V̇o2peak) was assessed via maximal treadmill exercise testing with concomitant blood pressure monitoring. All measurements were performed at baseline and after the 12-wk intervention. A linear mixed model was used to compare the rate of increase in blood pressure during the test. RHI improved with exercise (Pre = 1.78 ± 0.10 vs. Post = 2.01 ± 0.13, P = 0.03) with no change following stretching (Pre = 1.73 ± 0.08 vs. Post = 1.67 ± 0.10, P = 0.69). Peak systolic blood pressure during the maximal treadmill exercise test was lower after exercise training (Pre = 186 ± 5 mmHg, Post = 174 ± 4 mmHg, P = 0.003) with no change after stretching (Pre = 190 ± 6 mmHg, Post = 190 ± 4 mmHg, P = 0.12). The rate of increase in systolic blood pressure during the V̇o2peak test tended to decrease after training for both groups (-2 mmHg/stage) with no differences between groups (P = 0.97). There was no change in V̇o2peak after either intervention. In conclusion, aerobic exercise training improves endothelial function and attenuates peak blood pressure reactivity during exercise in CKD.NEW & NOTEWORTHY Patients with chronic kidney disease (CKD) exhibit increased blood pressure reactivity during exercise that is associated with endothelial dysfunction. Twelve weeks of structured, aerobic, exercise training improves endothelial function and attenuates peak blood pressure responses during exercise in CKD stages III-IV.


Asunto(s)
Ejercicio Físico , Insuficiencia Renal Crónica , Presión Sanguínea/fisiología , Ejercicio Físico/fisiología , Prueba de Esfuerzo , Terapia por Ejercicio , Femenino , Humanos , Masculino , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia
8.
Kidney Blood Press Res ; 47(2): 103-112, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34758473

RESUMEN

BACKGROUND: Chronic kidney disease (CKD) patients have exercise intolerance and exaggerated blood pressure reactivity during exercise that are mediated by sympathetic nervous system (SNS) overactivation and decreased nitric oxide (NO) bioavailability. The activation of the renin-angiotensin system (RAS) increases SNS activation and reduces NO synthesis, and prior studies suggest that RAS blockade attenuates declines in physical function. We hypothesized that RAS inhibitor (RASi) use is associated with higher exercise capacity mediated by decreased SNS activity and increased NO-dependent endothelial function in CKD. METHOD: In 35 CKD patients (57 ± 7 years) and 20 controls (CONs) (53 ± 8 years), we measured exercise capacity (peak oxygen consumption [VO2peak]), muscle sympathetic nervous activity (MSNA), and flow-mediated dilation (FMD) for NO-dependent endothelial function. RESULTS: CKD patients treated with RASi (CKD + RASi, n = 25) had greater VO2peak than CKD patients not treated with RASi (CKD no RASi, n = 10), but lower VO2peak than CONs (23.3 ± 5.8 vs. 16.4 ± 2.9, p = 0.007; vs. 30.0 ± 7.7, p = 0.016 mL/min/kg, respectively). CKD + RASi had lower resting MSNA and greater FMD than CKD no RASi. Compared to CONs, CKD + RASi had similar MSNA but lower FMD. VO2peak was positively associated with FMD (r = 0.417, p = 0.038) and was predicted by the combination of FMD and RASi status (r2 = 0.344, p = 0.01) and MSNA and RASi status (r2 = 0.575, p = 0.040) in CKD patients. CONCLUSION: In summary, CKD patients with RASi have higher exercise capacity than those not on RASi. Higher exercise capacity in the RASi-treated group was associated with lower resting SNS activity and higher NO-dependent vascular endothelial function.


Asunto(s)
Insuficiencia Renal Crónica , Sistema Renina-Angiotensina , Presión Sanguínea , Tolerancia al Ejercicio , Humanos , Insuficiencia Renal Crónica/tratamiento farmacológico , Sistema Nervioso Simpático
9.
Front Physiol ; 12: 642850, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33815146

RESUMEN

Cerebrovascular control and its integration with other physiological systems play a key role in the effective maintenance of homeostasis in brain functioning. Maintenance, restoration, and promotion of such a balance are one of the paramount goals of brain rehabilitation and intervention programs. Cerebrovascular reactivity (CVR), an index of cerebrovascular reserve, plays an important role in chemo-regulation of cerebral blood flow. Improved vascular reactivity and cerebral blood flow are important factors in brain rehabilitation to facilitate desired cognitive and functional outcomes. It is widely accepted that CVR is impaired in aging, hypertension, and cerebrovascular diseases and possibly in neurodegenerative syndromes. However, a multitude of physiological factors influence CVR, and thus a comprehensive understanding of underlying mechanisms are needed. We are currently underinformed on which rehabilitation method will improve CVR, and how this information can inform on a patient's prognosis and diagnosis. Implementation of targeted rehabilitation regimes would be the first step to elucidate whether such regimes can modulate CVR and in the process may assist in improving our understanding for the underlying vascular pathophysiology. As such, the high spatial resolution along with whole brain coverage offered by MRI has opened the door to exciting recent developments in CVR MRI. Yet, several challenges currently preclude its potential as an effective diagnostic and prognostic tool in treatment planning and guidance. Understanding these knowledge gaps will ultimately facilitate a deeper understanding for cerebrovascular physiology and its role in brain function and rehabilitation. Based on the lessons learned from our group's past and ongoing neurorehabilitation studies, we present a systematic review of physiological mechanisms that lead to impaired CVR in aging and disease, and how CVR imaging and its further development in the context of brain rehabilitation can add value to the clinical settings.

10.
J Appl Physiol (1985) ; 130(6): 1786-1797, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33914663

RESUMEN

Trauma-induced hemorrhage is a leading cause of disability and death due, in part, to impaired perfusion and oxygenation of the brain. It is unknown if cerebrovascular responses to blood loss are differentiated based on sex. We hypothesized that compared to males, females would have reduced tolerance to simulated hemorrhage induced by maximal lower body negative pressure (LBNP), and this would be associated with an earlier reduction in cerebral blood flow and cerebral oxygenation. Healthy young males (n = 29, 26 ± 4 yr) and females (n = 23, 27 ± 5 yr) completed a step-wise LBNP protocol to presyncope. Mean arterial pressure (MAP), stroke volume (SV), middle cerebral artery velocity (MCAv), end-tidal CO2 (etCO2), and cerebral oxygen saturation (ScO2) were measured continuously. Unexpectedly, tolerance to LBNP was similar between the sexes (males, 1,604 ± 68 s vs. females, 1,453 ± 78 s; P = 0.15). Accordingly, decreases (%Δ) in MAP, SV, MCAv, and ScO2 were similar between males and females throughout LBNP and at presyncope (P ≥ 0.20). Interestingly, although decreases in etCO2 were similar between the sexes throughout LBNP (P = 0.16), at presyncope, the %Δ etCO2 from baseline was greater in males compared to females (-30.8 ± 2.6% vs. -21.3 ± 3.0%; P = 0.02). Contrary to our hypothesis, sex does not influence tolerance, or the central or cerebral hemodynamic responses to simulated hemorrhage. However, the etCO2 responses at presyncope do suggest potential sex differences in cerebral vascular sensitivity to CO2 during central hypovolemia.NEW & NOTEWORTHY Tolerance and cerebral blood velocity responses to simulated hemorrhage (elicited by lower body negative pressure) were similar between male and female subjects. Interestingly, the change in etCO2 from baseline was greater in males compared to females at presyncope, suggesting potential sex differences in cerebral vascular sensitivity to CO2 during simulated hemorrhage. These findings may facilitate development of individualized therapeutic interventions to improve survival from hemorrhagic injuries in both men and women.


Asunto(s)
Hipovolemia , Presión Negativa de la Región Corporal Inferior , Presión Sanguínea , Circulación Cerebrovascular , Femenino , Hemodinámica , Humanos , Masculino , Arteria Cerebral Media
12.
Top Stroke Rehabil ; 28(4): 251-257, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-32783602

RESUMEN

BACKGROUND: Stroke survivors have exercise intolerance that contributes to reduced quality of life and survival. While exaggerated blood pressure responses during exercise have been documented in other chronic diseases, whether stroke patients have abnormal hemodynamic responses during aerobic exercise remains unexplored. OBJECTIVES: This cross-sectional study aimed to examine whether stroke survivors have exaggerated increases in blood pressure during maximal treadmill exercise and whether these responses may be related to systemic inflammation. METHODS: Forty-six participants (25 stroke survivors, STROKE, and 21 controls, CON) performed a maximal treadmill exercise test via the modified Naughton protocol while blood pressure was measured manually during each treadmill stage. A linear mixed model was used to compare the slope of rise in heart rate and blood pressure within and between groups. Spearmans rho analysis was performed to explore the relationship between these responses and circulating concentrations of inflammatory biomarkers. RESULTS: The STROKE group exhibited a lower VO2peak (16.4 ± 0.8 vs. 30.0 ± 1.8 ml/kg/min, P < .001) and a greater rate of increase in systolic blood pressure compared to CON (17.4 ± 1.5 vs. 9.9 ± 1.4 mmHg/stage, P < .001). We observed no relationship; however, between inflammatory biomarkers and the exaggerated hemodynamic responses in the STROKE group. CONCLUSION: In conclusion, stroke survivors exhibit greater increases in systolic blood pressure during maximal treadmill exercise compared to controls. These responses do not appear to be related to systemic inflammation. Future work should seek to delineate the mechanisms responsible for exaggerated blood pressure responses during exercise in stroke.


Asunto(s)
Prueba de Esfuerzo , Accidente Cerebrovascular , Estudios Transversales , Ejercicio Físico , Humanos , Inflamación/etiología , Calidad de Vida , Accidente Cerebrovascular/complicaciones , Sobrevivientes
13.
J Appl Physiol (1985) ; 130(2): 380-389, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33211600

RESUMEN

Lower body negative pressure (LBNP) elicits central hypovolemia, and it has been used to simulate the cardiovascular and cerebrovascular responses to hemorrhage in humans. LBNP protocols commonly use progressive stepwise reductions in chamber pressure for specific time periods. However, continuous ramp LBNP protocols have also been utilized to simulate the continuous nature of most bleeding injuries. The aim of this study was to compare tolerance and hemodynamic responses between these two LBNP profiles. Healthy human subjects (N = 19; age, 27 ± 4 y; 7 female/12 male) completed a 1) step LBNP protocol (5-min steps) and 2) continuous ramp LBNP protocol (3 mmHg/min), both to presyncope. Heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), middle and posterior cerebral artery velocity (MCAv and PCAv), cerebral oxygen saturation (ScO2), and end-tidal CO2 (etCO2) were measured. LBNP tolerance, via the cumulative stress index (CSI, summation of chamber pressure × time at each pressure), and hemodynamic responses were compared between the two protocols. The CSI (step: 911 ± 97 mmHg/min vs. ramp: 823 ± 83 mmHg/min; P = 0.12) and the magnitude of central hypovolemia (%Δ SV, step: -54.6% ± 2.6% vs. ramp: -52.1% ± 2.8%; P = 0.32) were similar between protocols. Although there were no differences between protocols for the maximal %Δ HR (P = 0.88), the %Δ MAP during the step protocol was attenuated (P = 0.05), and the reductions in MCAv, PCAv, ScO2, and etCO2 were greater (P ≤ 0.08) when compared with the ramp protocol at presyncope. These results indicate that when comparing cardiovascular responses to LBNP across different laboratories, the specific pressure profile must be considered as a potential confounding factor.NEW & NOTEWORTHY Ramp lower body negative pressure (LBNP) protocols have been utilized to simulate the continuous nature of bleeding injuries. However, it unknown if tolerance or the physiological responses to ramp LBNP are similar to the more common stepwise LBNP protocol. We report similar tolerance between the two protocols, but the step protocol elicited a greater increase in cerebral oxygen extraction in the presence of reduced blood flow, presumably facilitating the matching of metabolic supply and demand.


Asunto(s)
Circulación Cerebrovascular , Presión Negativa de la Región Corporal Inferior , Adulto , Presión Sanguínea , Femenino , Frecuencia Cardíaca , Hemorragia , Humanos , Hipovolemia , Masculino , Arteria Cerebral Media , Adulto Joven
14.
Am J Physiol Renal Physiol ; 319(5): F782-F791, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32985235

RESUMEN

Patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) experience an increased risk of cerebrovascular disease and cognitive dysfunction. Hemodialysis (HD), a major modality of renal replacement therapy in ESKD, can cause rapid changes in blood pressure, osmolality, and acid-base balance that collectively present a unique stress to the cerebral vasculature. This review presents an update regarding cerebral blood flow (CBF) regulation in CKD and ESKD and how the maintenance of cerebral oxygenation may be compromised during HD. Patients with ESKD exhibit decreased cerebral oxygen delivery due to anemia, despite cerebral hyperperfusion at rest. Cerebral oxygenation further declines during HD due to reductions in CBF, and this may induce cerebral ischemia or "stunning." Intradialytic reductions in CBF are driven by decreases in cerebral perfusion pressure that may be partially opposed by bicarbonate shifts during dialysis. Intradialytic reductions in CBF have been related to several variables that are routinely measured in clinical practice including ultrafiltration rate and blood pressure. However, the role of compensatory cerebrovascular regulatory mechanisms during HD remains relatively unexplored. In particular, cerebral autoregulation can oppose reductions in CBF driven by reductions in systemic blood pressure, while cerebrovascular reactivity to CO2 may attenuate intradialytic reductions in CBF through promoting cerebral vasodilation. However, whether these mechanisms are effective in ESKD and during HD remain relatively unexplored. Important areas for future work include investigating potential alterations in cerebrovascular regulation in CKD and ESKD and how key regulatory mechanisms are engaged and integrated during HD to modulate intradialytic declines in CBF.


Asunto(s)
Circulación Cerebrovascular/fisiología , Hipotensión/fisiopatología , Fallo Renal Crónico/fisiopatología , Insuficiencia Renal Crónica/fisiopatología , Presión Sanguínea/fisiología , Encéfalo/fisiopatología , Homeostasis/fisiología , Humanos , Diálisis Renal/efectos adversos
15.
Am J Physiol Regul Integr Comp Physiol ; 319(6): R611-R616, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-32966119

RESUMEN

Posttraumatic stress disorder (PTSD) is an independent risk factor for the development of hypertension and cardiovascular disease. Patients with PTSD have heightened blood pressure and sympathetic nervous system reactivity; however, it is unclear if patients with PTSD have exaggerated vasoconstriction in response to sympathetic nerve activation that could also contribute to increased blood pressure reactivity. Therefore, we hypothesized that patients with PTSD have increased sensitivity of vascular α1-adrenergic receptors (α1ARs), the major mediators of vasoconstriction in response to release of norepinephrine at sympathetic nerve terminals. To assess vascular α1AR sensitivity, we measured the degree of venoconstriction in a dorsal hand vein in response to exponentially increasing doses of the selective α1AR agonist, phenylephrine (PE), in 9 patients with PTSD (age = 59 ± 2 yr) and 10 age-matched controls (age = 60 ± 1 yr). Individual dose-response curves were generated to determine the dose of PE that induces 50% of maximal venoconstriction (i.e., PE ED50) reflective of vascular α1AR sensitivity. In support of our hypothesis, PE ED50 values were lower in PTSD compared with controls (245 ± 54 ng/min vs. 1,995 ± 459 ng/min, P = 0.012), indicating increased vascular α1AR sensitivity in PTSD. The PTSD group also had an increase in slope of rise in venoconstriction, indicative of an altered venoconstrictive reactivity to PE compared with controls (19.8% ± 1.2% vs. 15.1% ± 1.2%, P = 0.009). Heightened vascular α1AR sensitivity in PTSD may contribute to augmented vasoconstriction and blood pressure reactivity to sympathoexcitation and to increased cardiovascular disease risk in this patient population.


Asunto(s)
Envejecimiento/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Trastornos por Estrés Postraumático/metabolismo , Sistema Nervioso Simpático/metabolismo , Vasoconstricción , Agonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Factores de Edad , Presión Sanguínea , Estudios de Casos y Controles , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Fenilefrina/administración & dosificación , Receptores Adrenérgicos alfa 1/efectos de los fármacos , Transducción de Señal , Trastornos por Estrés Postraumático/fisiopatología , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/fisiopatología , Vasoconstricción/efectos de los fármacos
16.
Am J Physiol Regul Integr Comp Physiol ; 319(4): R466-R475, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32847397

RESUMEN

Posttraumatic stress disorder (PTSD) is characterized by increased risk for developing hypertension and cardiovascular disease. We recently showed that device-guided slow breathing (DGB) acutely lowers blood pressure (BP) and muscle sympathetic activity (MSNA) and improves baroreflex sensitivity (BRS) in PTSD. The aim of this study was to assess the long-term benefits of DGB on autonomic function at rest and during stress. We hypothesized that long-term DGB improves arterial BRS and lowers BP and MSNA in PTSD. Twenty-five veterans with PTSD were studied and randomized to either 8 wk of daily DGB (n = 12) or 8 wk of sham device (Sham; n = 13). BP, heart rate (HR), and MSNA were measured at rest and during mental math. Arterial BRS was assessed using the modified Oxford technique. Resting MSNA, BP, and heart rate (HR) remained comparable before and after 8 wk in both groups (DGB and Sham). Likewise, the change in sympathetic and cardiovagal BRS was not different between the groups. Interestingly, DGB significantly decreased MSNA reactivity to mental math when expressed as burst frequency (P = 0.012) or burst incidence (P = 0.008) compared with Sham, suggesting a sustained effect of DGB on sympathetic reactivity to stress in PTSD. Contrary to our hypothesis, long-term DGB did not lower systolic BP, diastolic BP, or HR responses to stress compared with Sham. Likewise, pulse pressure reactivity after 8 wk (P = 0.121) was also comparable. In summary, these data suggest that long-term use of DGB may lead to a sustained dampening of sympathetic reactivity to mental stress in PTSD.


Asunto(s)
Barorreflejo/fisiología , Respiración , Trastornos por Estrés Postraumático/fisiopatología , Estrés Psicológico/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Adulto , Presión Sanguínea/fisiología , Método Doble Ciego , Femenino , Frecuencia Cardíaca/fisiología , Hemodinámica/fisiología , Humanos , Masculino , Frecuencia Respiratoria , Veteranos
17.
Am J Physiol Regul Integr Comp Physiol ; 317(3): R485-R490, 2019 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-31314543

RESUMEN

Chronic kidney disease (CKD) is often complicated by difficult-to-control hypertension, in part due to chronic overactivation of the sympathetic nervous system (SNS). CKD patients also exhibit a greater increase in arterial blood pressure for a given increase in sympathetic nerve activation, suggesting an augmented vasoconstrictive response to SNS activation (i.e., neurovascular transduction). One potential mechanism of increased sympathetic neurovascular transduction is heightened sensitivity of the vascular α1-adrenergic receptors (α1ARs), the major effectors of vasoconstriction in response to norepinephrine release at the sympathetic nerve terminals. Therefore, we hypothesized that patients with CKD have increased vascular α1AR sensitivity. We studied 32 patients with CKD stages III and IV (age 59.9 ± 1.3 yr) and 19 age-matched controls (CON, age 63.2 ± 1.6 yr). Using a linear variable differential transformer (LVDT), we measured change in venoconstriction in response to exponentially increasing doses of the selective α1AR agonist phenylephrine (PE) administered sequentially into a dorsal hand vein. Individual semilogarithmic PE dose-response curves were constructed for each participant to determine the PE dose at which 50% of maximum venoconstriction occurred (ED50), reflecting α1AR sensitivity. In support of our hypothesis, CKD patients had a lower PE ED50 than CON (CKD = 2.23 ± 0.11 vs. CON = 2.63 ± 0.20, P = 0.023), demonstrating increased vascular α1AR sensitivity. Additionally, CKD patients had a greater venoconstrictive capacity to PE than CON (P = 0.015). Augmented α1AR sensitivity may contribute mechanistically to enhanced neurovascular transduction in CKD and may explain, in part, the greater blood pressure reactivity exhibited in these patients.


Asunto(s)
Fenilefrina/farmacología , Receptores Adrenérgicos alfa 1/metabolismo , Insuficiencia Renal Crónica/fisiopatología , Vasoconstricción/fisiología , Agonistas de Receptores Adrenérgicos alfa 1/farmacología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vasoconstricción/efectos de los fármacos
18.
Exp Physiol ; 104(8): 1190-1201, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31090115

RESUMEN

NEW FINDINGS: What is the central question of this study? Do low-frequency oscillations in arterial pressure and cerebral blood velocity protect cerebral blood velocity and oxygenation during central hypovolaemia? What is the main finding and its importance? Low-frequency oscillations in arterial pressure and cerebral blood velocity attenuate reductions in cerebral oxygen saturation but do not protect absolute cerebral blood velocity during central hypovolaemia. This finding indicates the potential importance of haemodynamic oscillations in maintaining cerebral oxygenation and therefore viability of tissues during challenges to cerebral blood flow and oxygen delivery. ABSTRACT: Tolerance to both real and simulated haemorrhage varies between individuals. Exaggerated low-frequency (∼0.1 Hz) oscillations in mean arterial pressure and brain blood flow [indexed via middle cerebral artery velocity (MCAv)] have been associated with improved tolerance to reduced central blood volume. The mechanism for this association has not been explored. We hypothesized that inducing low-frequency oscillations in arterial pressure and cerebral blood velocity would attenuate reductions in cerebral blood velocity and oxygenation during simulated haemorrhage. Fourteen subjects (11 men and three women) were exposed to oscillatory (0.1 and 0.05 Hz) and non-oscillatory (0 Hz) lower-body negative pressure profiles with an average chamber pressure of -60 mmHg (randomized and counterbalanced order). Measurements included arterial pressure and stroke volume via finger photoplethysmography, MCAv via transcranial Doppler ultrasound, and cerebral oxygenation of the frontal lobe via near-infrared spectroscopy. Tolerance was higher during the two oscillatory profiles compared with the 0 Hz profile (0.05 Hz, P = 0.04; 0.1 Hz, P = 0.09), accompanied by attenuated reductions in stroke volume (P < 0.001) and cerebral oxygenation of the frontal lobe (P ≤ 0.02). No differences were observed between profiles for reductions in mean arterial pressure (P = 0.17) and MCAv (P = 0.30). In partial support of our hypothesis, cerebral oxygenation, but not cerebral blood velocity, was protected during the oscillatory profiles. Interestingly, more subjects tolerated the oscillatory profiles compared with the static 0 Hz profile, despite similar arterial pressure responses. These findings emphasize the potential importance of haemodynamic oscillations in maintaining perfusion and oxygenation of cerebral tissues during haemorrhagic stress.


Asunto(s)
Velocidad del Flujo Sanguíneo/fisiología , Circulación Cerebrovascular/fisiología , Oxígeno/metabolismo , Adulto , Presión Arterial/fisiología , Encéfalo/metabolismo , Encéfalo/fisiología , Femenino , Humanos , Presión Negativa de la Región Corporal Inferior/métodos , Masculino , Arteria Cerebral Media/fisiología , Espectroscopía Infrarroja Corta/métodos , Volumen Sistólico/fisiología , Ultrasonografía Doppler Transcraneal/métodos
19.
Am J Physiol Regul Integr Comp Physiol ; 317(2): R312-R318, 2019 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31141417

RESUMEN

Chronic kidney disease (CKD) patients experience augmented blood pressure (BP) reactivity during exercise that is associated with an increased risk of cardiovascular mortality. Exaggerated exercise pressor responses in CKD are in part mediated by augmented sympathetic nerve activation due to heightened muscle mechanoreflex. One mechanism that may lead to sensitization of the muscle mechanoreflex in CKD is metabolic acidosis. We hypothesized that CKD patients with low serum [bicarbonate] would exhibit exaggerated increases in arterial BP, greater reductions in muscle interstitial pH, and fatigue earlier during exercise compared with CKD patients with normal serum bicarbonate concentration ([bicarbonate]). Eighteen CKD participants with normal serum [bicarbonate] (≥24 mmol/l, normal-bicarb) and 9 CKD participants with mild metabolic acidosis ([bicarbonate] range 20-22 mmol/l, low-bicarb) performed rhythmic handgrip (RHG) exercise to volitional fatigue at 40% of maximal voluntary contraction. BP, heart rate, and muscle interstitial pH using near infrared spectroscopy were measured continuously. While mean arterial pressure (MAP) increased with exercise in both groups (P ≤ 0.002), CKD with low-bicarb had an exaggerated MAP response compared with CKD with normal-bicarb (+5.9 ± 1.3 mmHg/30 s vs. +2.6 ± 0.5 mmHg/30 s, P = 0.01). The low-bicarb group reached exhaustion earlier than the normal-bicarb group (179 ± 21 vs. 279 ± 19 s, P = 0.003). There were no differences in the change in muscle interstitial pH during exercise between groups (P = 0.31). CKD patients with metabolic acidosis have augmented exercise-induced increases in BP and poorer exercise tolerance. There was no difference in change in muscle interstitial pH between groups, however, suggesting that augmented exercise BP responses in metabolic acidosis are not due to impaired muscle-buffering capacity.


Asunto(s)
Acidosis/metabolismo , Ejercicio Físico/fisiología , Fuerza de la Mano/fisiología , Insuficiencia Renal Crónica/fisiopatología , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Frecuencia Cardíaca/fisiología , Humanos , Hipertensión/fisiopatología , Músculo Esquelético/metabolismo , Sistema Nervioso Simpático/fisiopatología
20.
Am J Physiol Regul Integr Comp Physiol ; 316(5): R504-R511, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-30726117

RESUMEN

Patients with end-stage renal disease (ESRD) have decreased exercise capacity and exercise intolerance that contribute to cardiovascular risk. One potential mechanism underlying exercise intolerance in ESRD is impaired ability to oppose sympathetically mediated vasoconstriction within exercising skeletal muscle (i.e., functional sympatholysis, FS). We hypothesized that ESRD patients have impaired FS compared with healthy (CON) and hypertensive (HTN) controls and that impaired FS is related to circulating levels of the uremic toxin asymmetric dimethyl arginine (ADMA), an endogenous nitric oxide synthase inhibitor. Near-infrared spectroscopy-derived oxygen tissue saturation index (TSI) of the forearm muscle was measured continuously in 33 participants (9 CON, 14 HTN, 10 ESRD) at rest and during low-dose (-20 mmHg) lower body negative pressure (LBNP), moderate rhythmic handgrip exercise, and LBNP with concomitant handgrip exercise (LBNP+handgrip). Resting muscle TSI was lower in ESRD than in CON and HTN groups (CON = 67.8 ± 1.9%, HTN = 67.2 ± 1.1%, ESRD = 62.7 ± 1.5%, P = 0.03). Whereas CON and HTN groups had an attenuation in sympathetically mediated reduction in TSI during LBNP + handgrip compared with LBNP alone (P ≤ 0.05), this response was not present in ESRD (P = 0.71), suggesting impaired FS. There was no difference in plasma [ADMA] between groups (CON = 0.47 ± 0.05 µmol/l, HTN = 0.42 ± 0.06 µmol/l, ESRD = 0.63 ± 0.14 µmol/l, P = 0.106) and no correlation between plasma [ADMA] and resting muscle TSI (P = 0.84) or FS (P = 0.75). Collectively, these findings suggest that ESRD patients have lower muscle perfusion at rest and impaired FS but that these derangements are not related to circulating [ADMA].


Asunto(s)
Vasos Sanguíneos/inervación , Tolerancia al Ejercicio , Fallo Renal Crónico/fisiopatología , Músculo Esquelético/irrigación sanguínea , Sistema Nervioso Simpático/fisiopatología , Vasoconstricción , Adulto , Arginina/análogos & derivados , Arginina/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Antebrazo , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Contracción Muscular , Flujo Sanguíneo Regional , Diálisis Renal
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