RESUMEN
Sympathetic transduction is reduced following chronic high-altitude (HA) exposure; however, vascular α-adrenergic signaling, the primary mechanism mediating sympathetic vasoconstriction at sea level (SL), has not been examined at HA. In nine male lowlanders, we measured forearm blood flow (Doppler ultrasound) and calculated changes in vascular conductance (ΔFVC) during 1) incremental intra-arterial infusion of phenylephrine to assess α1-adrenergic receptor responsiveness and 2) combined intra-arterial infusion of ß-adrenergic and α-adrenergic antagonists propranolol and phentolamine (α-ß-blockade) to assess adrenergic vascular restraint at rest and during exercise-induced sympathoexcitation (cycling; 60% peak power). Experiments were performed near SL (344 m) and after 3 wk at HA (4,383 m). HA abolished the vasoconstrictor response to low-dose phenylephrine (ΔFVC: SL: -34 ± 15%, vs. HA; +3 ± 18%; P < 0.0001) and markedly attenuated the response to medium (ΔFVC: SL: -45 ± 18% vs. HA: -28 ± 11%; P = 0.009) and high (ΔFVC: SL: -47 ± 20%, vs. HA: -35 ± 20%; P = 0.041) doses. Blockade of ß-adrenergic receptors alone had no effect on resting FVC (P = 0.500) and combined α-ß-blockade induced a similar vasodilatory response at SL and HA (P = 0.580). Forearm vasoconstriction during cycling was not different at SL and HA (P = 0.999). Interestingly, cycling-induced forearm vasoconstriction was attenuated by α-ß-blockade at SL (ΔFVC: Control: -27 ± 128 vs. α-ß-blockade: +19 ± 23%; P = 0.0004), but unaffected at HA (ΔFVC: Control: -20 ± 22 vs. α-ß-blockade: -23 ± 11%; P = 0.999). Our results indicate that in healthy males, altitude acclimatization attenuates α1-adrenergic receptor responsiveness; however, resting α-adrenergic restraint remains intact, due to concurrent resting sympathoexcitation. Furthermore, forearm vasoconstrictor responses to cycling are preserved, although the contribution of adrenergic receptors is diminished, indicating a reliance on alternative vasoconstrictor mechanisms.
Asunto(s)
Adrenérgicos , Vasoconstricción , Masculino , Humanos , Adrenérgicos/farmacología , Vasoconstrictores/farmacología , Fenilefrina/farmacología , Flujo Sanguíneo Regional , Músculo Esquelético/fisiología , HipoxiaRESUMEN
PURPOSE: Resistance training (RT) is an effective countermeasure to combat physical deconditioning whereby localized hypoxia within the limb increases metabolic stress eliciting muscle adaptation. The current study sought to examine the influence of gravity on muscle oxygenation (SmO2) alongside vascular hemodynamic responses. METHODS: In twelve young healthy adults, an ischemic occlusion test and seven minutes of low-intensity rhythmic plantarflexion exercise were used alongside superficial femoral blood flow and calf near-infrared spectroscopy to assess the microvascular vasodilator response, conduit artery flow-mediated dilation, exercise-induced hyperemia, and SmO2 with the leg positioned above or below the heart in a randomized order. RESULTS: The microvascular vasodilator response, assessed by peak blood flow (798 ± 231 mL/min vs. 1348 ± 290 mL/min; p < 0.001) and reperfusion slope 10 s of SmO2 after cuff deflation (0.75 ± 0.45%.s-1 vs.2.40 ± 0.94%.s-1; p < 0.001), was attenuated with the leg above the heart. This caused a blunted dilatation of the superficial femoral artery (3.0 ± 2.4% vs. 5.2 ± 2.1%; p = 0.008). Meanwhile, blood flow area under the curve was comparable (above the heart: 445 ± 147 mL vs. below the heart: 474 ± 118 mL; p = 0.55) in both leg positions. During rhythmic exercise, the increase in femoral blood flow was lower in the leg up position (above the heart: 201 ± 94% vs. below the heart: 292 ± 114%; p = 0.001) and contributed to a lower SmO2 (above the heart: 41 ± 18% vs. below the heart 67 ± 5%; p < 0.001). CONCLUSION: Positioning the leg above the heart results in attenuated peak vascular dilator response and exercise-induced hyperemia that coincided with a lower SmO2 during low-intensity plantarflexion exercise.
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Hiperemia , Pierna , Adulto , Humanos , Pierna/irrigación sanguínea , Músculo Esquelético/fisiología , Flujo Sanguíneo Regional/fisiología , Vasodilatadores , HemodinámicaRESUMEN
Chronic exposure to hypoxia (high-altitude, HA; >4000 m) attenuates the vasodilatory response to exercise and is associated with a persistent increase in basal sympathetic nerve activity (SNA). The mechanism(s) responsible for the reduced vasodilatation and exercise hyperaemia at HA remains unknown. We hypothesized that heightened adrenergic signalling restrains skeletal muscle blood flow during handgrip exercise in lowlanders acclimatizing to HA. We tested nine adult males (n = 9) at sea-level (SL; 344 m) and following 21-28 days at HA (â¼4300 m). Forearm blood flow (FBF; duplex ultrasonography), mean arterial pressure (MAP; brachial artery catheter), forearm vascular conductance (FVC; FBF/MAP), and arterial and venous blood sampling (O2 delivery ( DO2${D}_{{{\rm{O}}}_{\rm{2}}}$ ) and uptake ( VÌO2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ )) were measured at rest and during graded rhythmic handgrip exercise (5%, 15% and 25% of maximum voluntary isometric contraction; MVC) before and after local α- and ß-adrenergic blockade (intra-arterial phentolamine and propranolol). HA reduced ΔFBF (25% MVC: SL: 138.3 ± 47.6 vs. HA: 113.4 ± 37.1 ml min-1 ; P = 0.022) and Δ VÌO2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ (25% MVC: SL: 20.3 ± 7.5 vs. HA: 14.3 ± 6.2 ml min-1 ; P = 0.014) during exercise. Local adrenoreceptor blockade at HA restored FBF during exercise (25% MVC: SLα-ß blockade : 164.1 ± 71.7 vs. HAα-ß blockade : 185.4 ± 66.6 ml min-1 ; P = 0.947) but resulted in an exaggerated relationship between DO2${D}_{{{\rm{O}}}_{\rm{2}}}$ and VÌO2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ( DO2${D}_{{{\rm{O}}}_{\rm{2}}}$ / VÌO2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ slope: SL: 1.32; HA: slope: 1.86; P = 0.037). These results indicate that tonic adrenergic signalling restrains exercise hyperaemia in lowlanders acclimatizing to HA. The increase in adrenergic restraint is necessary to match oxygen delivery to demand and prevent over perfusion of contracting muscle at HA. KEY POINTS: In exercising skeletal muscle, local vasodilatory signalling and sympathetic vasoconstriction integrate to match oxygen delivery to demand and maintain arterial blood pressure. Exposure to chronic hypoxia (altitude, >4000 m) causes a persistent increase in sympathetic nervous system activity that is associated with impaired functional capacity and diminished vasodilatation during exercise. In healthy male lowlanders exposed to chronic hypoxia (21-28 days; â¼4300 m), local adrenoreceptor blockade (combined α- and ß-adrenergic blockade) restored skeletal muscle blood flow during handgrip exercise. However, removal of tonic adrenergic restraint at high altitude caused an excessive rise in blood flow and subsequently oxygen delivery for any given metabolic demand. This investigation is the first to identify greater adrenergic restraint of blood flow during acclimatization to high altitude and provides evidence of a functional role for this adaptive response in regulating oxygen delivery and demand.
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Altitud , Hiperemia , Adrenérgicos , Adulto , Fuerza de la Mano/fisiología , Humanos , Hiperemia/metabolismo , Hipoxia , Masculino , Músculo Esquelético/fisiología , Oxígeno/metabolismo , Flujo Sanguíneo Regional/fisiologíaRESUMEN
Andeans with chronic mountain sickness (CMS) and polycythemia have similar maximal oxygen uptakes to healthy Andeans. Therefore, this study aimed to explore potential adaptations in convective oxygen transport, with a specific focus on sympathetically mediated vasoconstriction of nonactive skeletal muscle. In Andeans with (CMS+, n = 7) and without (CMS-, n = 9) CMS, we measured components of convective oxygen delivery, hemodynamic (arterial blood pressure via intra-arterial catheter), and autonomic responses [muscle sympathetic nerve activity (MSNA)] at rest and during steady-state submaximal cycling exercise [30% and 60% peak power output (PPO) for 5 min each]. Cycling caused similar increases in heart rate, cardiac output, and oxygen delivery at both workloads between both Andean groups. However, at 60% PPO, CMS+ had a blunted reduction in Δtotal peripheral resistance (CMS-, -10.7 ± 3.8 vs. CMS+, -4.9 ± 4.1 mmHg·L-1·min-1; P = 0.012; d = 1.5) that coincided with a greater Δforearm vasoconstriction (CMS-, -0.2 ± 0.6 vs. CMS+, 1.5 ± 1.3 mmHg·mL-1·min-1; P = 0.008; d = 1.7) and a rise in Δdiastolic blood pressure (CMS-, 14.2 ± 7.2 vs. CMS+, 21.6 ± 4.2 mmHg; P = 0.023; d = 1.2) compared with CMS-. Interestingly, although MSNA burst frequency did not change at 30% or 60% of PPO in either group, at 60% Δburst incidence was attenuated in CMS+ (P = 0.028; d = 1.4). These findings indicate that in Andeans with polycythemia, light intensity exercise elicited similar cardiovascular and autonomic responses compared with CMS-. Furthermore, convective oxygen delivery is maintained during moderate-intensity exercise despite higher peripheral resistance. In addition, the elevated peripheral resistance during exercise was not mediated by greater sympathetic neural outflow, thus other neural and/or nonneural factors are perhaps involved.NEW & NOTEWORTHY During submaximal exercise, convective oxygen transport is maintained in Andeans suffering from polycythemia. Light intensity exercise elicited similar cardiovascular and autonomic responses compared with healthy Andeans. However, during moderate-intensity exercise, we observed a blunted reduction in total peripheral resistance, which cannot be ascribed to an exaggerated increase in muscle sympathetic nerve activity, indicating possible contributions from other neural and/or nonneural mechanisms.
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Mal de Altura , Policitemia , Presión Sanguínea/fisiología , Enfermedad Crónica , Hemodinámica/fisiología , Humanos , Músculo Esquelético/inervación , Oxígeno , Sistema Nervioso SimpáticoRESUMEN
RATIONALE: Chronic exposure to hypoxia is associated with elevated sympathetic nervous activity and reduced vascular function in lowlanders, and Andean highlanders suffering from excessive erythrocytosis (EE); however, the mechanistic link between chronically elevated sympathetic nervous activity and hypoxia-induced vascular dysfunction has not been determined. OBJECTIVE: To determine the impact of heightened sympathetic nervous activity on resistance artery endothelial-dependent dilation (EDD), and endothelial-independent dilation, in lowlanders and Andean highlanders with and without EE. METHODS AND RESULTS: We tested healthy lowlanders (n=9) at sea level (344 m) and following 14 to 21 days at high altitude (4300 m), and permanent Andean highlanders with (n=6) and without (n=9) EE at high altitude. Vascular function was assessed using intraarterial infusions (3 progressive doses) of acetylcholine (ACh; EDD) and sodium nitroprusside (endothelial-independent dilation) before and after local α+ß adrenergic receptor blockade (phentolamine and propranolol). Intraarterial blood pressure, heart rate, and simultaneous brachial artery diameter and blood velocity were recorded at rest and during drug infusion. Changes in forearm vascular conductance were calculated. The main findings were (1) chronic hypoxia reduced EDD in lowlanders (changes in forearm vascular conductance from sea level: ACh1: -52.7±19.6%, ACh2: -25.4±38.7%, ACh3: -35.1±34.7%, all P≤0.02); and in Andeans with EE compared with non-EE (changes in forearm vascular conductance at ACh3: -36.4%, P=0.007). Adrenergic blockade fully restored EDD in lowlanders at high altitude, and normalized EDD between EE and non-EE Andeans. (2) Chronic hypoxia had no effect on endothelial-independent dilation in lowlanders, and no differences were detected between EE and non-EE Andeans; however, EID was increased in the non-EE Andeans after adrenergic blockade (P=0.012), but this effect was not observed in the EE Andeans. CONCLUSIONS: These data indicate that chronic hypoxia reduces EDD via heightened α-adrenergic signaling in lowlanders and in Andeans with EE. These vascular mechanisms have important implications for understanding the physiological consequences of acute and chronic high altitude adaptation.
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Adaptación Fisiológica , Mal de Altura/metabolismo , Policitemia/metabolismo , Receptores Adrenérgicos/metabolismo , Vasodilatación , Acetilcolina/metabolismo , Acetilcolina/farmacología , Adrenérgicos/farmacología , Adulto , Altitud , Mal de Altura/sangre , Mal de Altura/fisiopatología , Presión Sanguínea , Vasos Sanguíneos/efectos de los fármacos , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiopatología , Frecuencia Cardíaca , Humanos , Masculino , Nitroprusiato/farmacología , Fentolamina/farmacología , Policitemia/etiología , Policitemia/fisiopatología , Propranolol/farmacología , Transducción de Señal , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/metabolismo , Sistema Nervioso Simpático/fisiopatología , Vasodilatadores/farmacologíaRESUMEN
KEY POINTS: Humans suffering from polycythaemia undergo multiple circulatory adaptations including changes in blood rheology and structural and functional vascular adaptations to maintain normal blood pressure and vascular shear stresses, despite high blood viscosity. During exercise, several circulatory adaptations are observed, especially involving adrenergic and non-adrenergic mechanisms within non-active and active skeletal muscle to maintain exercise capacity, which is not observed in animal models. Despite profound circulatory stress, i.e. polycythaemia, several adaptations can occur to maintain exercise capacity, therefore making early identification of the disease difficult without overt symptomology. Pharmacological treatment of the background heightened sympathetic activity may impair the adaptive sympathetic response needed to match local oxygen delivery to active skeletal muscle oxygen demand and therefore inadvertently impair exercise capacity. ABSTRACT: Excessive haematocrit and blood viscosity can increase blood pressure, cardiac work and reduce aerobic capacity. However, past clinical investigations have demonstrated that certain human high-altitude populations suffering from excessive erythrocytosis, Andeans with chronic mountain sickness, appear to have phenotypically adapted to life with polycythaemia, as their exercise capacity is comparable to healthy Andeans and even with sea-level inhabitants residing at high altitude. By studying this unique population, which has adapted through natural selection, this study aimed to describe how humans can adapt to life with polycythaemia. Experimental studies included Andeans with (n = 19) and without (n = 17) chronic mountain sickness, documenting exercise capacity and characterizing the transport of oxygen through blood rheology, including haemoglobin mass, blood and plasma volume and blood viscosity, cardiac output, blood pressure and changes in total and local vascular resistances through pharmacological dissection of α-adrenergic signalling pathways within non-active and active skeletal muscle. At rest, Andeans with chronic mountain sickness had a substantial plasma volume contraction, which alongside a higher red blood cell volume, caused an increase in blood viscosity yet similar total blood volume. Moreover, both morphological and functional alterations in the periphery normalized vascular shear stress and blood pressure despite high sympathetic nerve activity. During exercise, blood pressure, cardiac work and global oxygen delivery increased similar to healthy Andeans but were sustained by modifications in both non-active and active skeletal muscle vascular function. These findings highlight widespread physiological adaptations that can occur in response to polycythaemia, which allow the maintenance of exercise capacity.
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Mal de Altura , Policitemia , Aclimatación , Altitud , Animales , Humanos , FenotipoRESUMEN
Background: This study aimed to evaluate a Multiple Stent Delivery System for provisional focal stenting of the femoropopliteal artery. Patient and methods: The LOCOMOTIVE EXTENDED study (Multi-LOC for flOw liMiting Outcomes after plain old balloon angioplasty and/or drug-coated balloon Treatment in the infrainguinal position with the objectIVE to implant multiple stent segments) is a prospective, single-arm, multicentre observational study. The Multi-LOC Multiple Stent Delivery System (B.Braun, Melsungen, Germany) was used for provisional focal stenting of the femoropopliteal artery. We enrolled 357 patients with 449 femoropopliteal lesions; all had flow-limiting dissections or recoil following angioplasty. Eligibility included Rutherford classification 2 to 5 with a de novo or non-stented restenotic femoropopliteal lesion undergoing plain balloon or drug-coated balloon angioplasty. The 6- and 12-month efficacy endpoints encompassed target lesion revascularisation and primary patency rates. Results: The mean patient age was 71 ± 10 years. The mean lesion length was 16.0 ± 9.7 cm; 44.5% were TASC II C/D lesions and 31.4% were chronic total occlusions. By operator choice, 45% of the patients underwent drug-coated balloon angioplasty. On average, 4.0 stents (each 13 mm long) were placed in each lesion, resulting in a scaffolding proportion of 56% of the total lesion length with a technical success rate of 98.3%. At 6 and 12 months, the freedom from clinically driven target lesion revascularisation was 95.5% and 88.7% and the primary patency rates were 88.7% and 82.3%, respectively. At 12 months, significant improvements were noted in Rutherford categories and ankle-brachial indices. In multiple regression analyses, both diabetes mellitus and no distal run-off vessel showed a trend toward worse TLR, while other factors such as DCB predilation or the lesion length were not predictive. Conclusions: The LOCOMOTIVE EXTENDED study demonstrated the safety and efficacy of the Multi-LOC stent system for focal provisional stenting of complex femoropopliteal lesions.
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Angioplastia de Balón , Enfermedad Arterial Periférica , Anciano , Anciano de 80 o más Años , Angioplastia de Balón/efectos adversos , Arteria Femoral/diagnóstico por imagen , Alemania , Humanos , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/terapia , Arteria Poplítea/diagnóstico por imagen , Estudios Prospectivos , Stents , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
Sympathetic vasoconstriction is mediated by α-adrenergic receptors under resting conditions. During exercise, increased sympathetic nerve activity (SNA) is directed to inactive and active skeletal muscle; however, it is unclear what mechanism(s) are responsible for vasoconstriction during large muscle mass exercise in humans. The aim of this study was to determine the contribution of α-adrenergic receptors to sympathetic restraint of inactive skeletal muscle and active skeletal muscle during cycle exercise in healthy humans. In ten male participants (18-35 yr), mean arterial pressure (intra-arterial catheter) and forearm vascular resistance (FVR) and conductance (FVC) were assessed during cycle exercise (60% total peak workload) alone and during combined cycle exercise + handgrip exercise (HGE) before and after intra-arterial blockade of α- and ß-adrenoreceptors via phentolamine and propranolol, respectively. Cycle exercise caused vasoconstriction in the inactive forearm that was attenuated ~80% with adrenoreceptor blockade (%ΔFVR, +81.7 ± 84.6 vs. +9.7 ± 30.7%; P = 0.05). When HGE was performed during cycle exercise, the vasodilatory response to HGE was restrained by ~40% (ΔFVC HGE, +139.3 ± 67.0 vs. cycle exercise: +81.9 ± 66.3 ml·min-1·100 mmHg-1; P = 0.03); however, the restraint of active skeletal muscle blood flow was not due to α-adrenergic signaling. These findings highlight that α-adrenergic receptors are the primary, but not the exclusive mechanism by which sympathetic vasoconstriction occurs in inactive and active skeletal muscle during exercise. Metabolic activity or higher sympathetic firing frequencies may alter the contribution of α-adrenergic receptors to sympathetic vasoconstriction. Finally, nonadrenergic vasoconstrictor mechanisms may be important for understanding the regulation of blood flow during exercise.NEW & NOTEWORTHY Sympathetic restraint of vascular conductance to inactive skeletal muscle is critical to maintain blood pressure during moderate- to high-intensity whole body exercise. This investigation shows that cycle exercise-induced restraint of inactive skeletal muscle vascular conductance occurs primarily because of activation of α-adrenergic receptors. Furthermore, exercise-induced vasoconstriction restrains the subsequent vasodilatory response to hand-grip exercise; however, the restraint of active skeletal muscle vasodilation was in part due to nonadrenergic mechanisms. We conclude that α-adrenergic receptors are the primary but not exclusive mechanism by which sympathetic vasoconstriction restrains blood flow in humans during whole body exercise and that metabolic activity modulates the contribution of α-adrenergic receptors.
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Antagonistas Adrenérgicos alfa/farmacología , Antagonistas Adrenérgicos beta/farmacología , Ejercicio Físico , Músculo Esquelético/fisiología , Sistema Nervioso Simpático/fisiología , Adulto , Presión Sanguínea , Humanos , Masculino , Contracción Muscular , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/inervación , Fentolamina/farmacología , Propranolol/farmacología , Flujo Sanguíneo Regional , Sistema Nervioso Simpático/efectos de los fármacos , Vasoconstricción , VasodilataciónRESUMEN
PURPOSE: We examined the effects of hypoxaemia on dynamic cerebral autoregulation (dCA) in lowlanders and Sherpa highlanders. We hypothesized that dCA in lowlanders would be reduced to a greater extent in the common carotid artery (CCA) compared to the internal carotid artery (ICA) during acute hypoxia at sea level and at high altitude, whereas Sherpa highlanders would have preserved dCA upon ascent to high altitude. METHODS: dCA was calculated as the change in cerebrovascular conductance during transient hypotension induced via dual thigh-cuff release. Data were collected in 13 healthy lowlanders in normobaric normoxia and hypoxia (FIO2 = 0.11) at sea-level (344 m), and the day after arrival at 3440 m and 5050 m. In addition, 10 healthy Sherpa highlanders were tested at Kathmandu (~ 1400 m), and the day after arrival at 3440 m and 5050 m. RESULTS: The main findings were that: (1) in lowlanders, dCA in the CCA and ICA were both reduced by ~ 35% during normobaric hypoxia exposure at sea-level (P = 0.06 and P = 0.04, respectively); (2) CCA and ICA dCA were both similarly attenuated by ~ 40% at 5050 m in lowlanders, but not 3440 m, compared to sea-level (both P = 0.04); and (3) in Sherpa, high altitude had no impact on CCA dCA (P = 0.275), indicating intact cerebral autoregulation. CONCLUSION: Herein, we provide novel evidence that dCA, assessed via Duplex ultrasound, was attenuated in lowlanders with exposure to normobaric and hypobaric hypoxia, whereas it is potentially preserved in the Sherpa. The clinical implications of attenuated dCA in lowlanders, and the adaptive significance of this response in the Sherpa highlanders, remains to be elucidated.
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Altitud , Circulación Cerebrovascular , Homeostasis , Adaptación Fisiológica , Adulto , Mal de Altura/fisiopatología , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
The purpose of the study was to assess if high-intensity interval training (HIIT) using functional exercises is as effective as traditional running HIIT in improving maximum oxygen uptake (VO2max) and muscular endurance. Fifteen healthy, moderately trained female (n = 11) and male (n= 4) participants (age 25.6 ± 2.6 years) were assigned to either running HIIT (HIIT-R; n = 8, 6 females, 2 males) or functional HIIT (HIIT-F; n = 7, 5 females, 2 males). Over a four-week period, both groups performed 14 exercise sessions of either HIIT-R or, HIIT-F consisting of 3-4 sets of low-volume HIIT (8x 20 s, 10 s rest; set rest: 5 min). Training heart rate (HR) data were collected throughout all training sessions. Mean and peak HR during the training sessions were significantly different (p = 0.018 and p = 0.022, respectively) between training groups, with HIIT-F eliciting lower HR responses than the HIIT-R. However, despite these differences in exercise HR, VO2max improved similarly (~13% for the HIIT-R versus ~11% for the HIIT-F, p=0.300). Muscular endurance (burpees and toes to bar) significantly improved (p =0.004 and p = 0.001, respectively) independent of training modality. These findings suggest that classic running HIIT and functional HIIT both improve VO2max and affect muscular endurance to the same extent despite a lower cardiovascular strain in the functional protocol.
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Entrenamiento de Intervalos de Alta Intensidad/métodos , Músculo Esquelético/fisiología , Consumo de Oxígeno/fisiología , Resistencia Física/fisiología , Carrera/fisiología , Adulto , Capacidad Cardiovascular/fisiología , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Percepción/fisiología , Esfuerzo Físico/fisiología , Adulto JovenRESUMEN
KEY POINTS: The reduced oxygen tension of high altitude compromises performance in lowlanders. In this environment, Sherpa display superior performance, but little is known on this issue. Sherpa present unique genotypic and phenotypic characteristics at the muscular level, which may enhance resistance to peripheral fatigue at high altitude compared to lowlanders. We studied the impact of gradual ascent and exposure to high altitude (5050 m) on peripheral fatigue in age-matched lowlanders and Sherpa, using intermittent electrically-evoked contractions of the knee extensors. Peripheral fatigue (force loss) was lower in Sherpa during the first part of the protocol. Post-protocol, the rate of force development and contractile impulse recovered faster in Sherpa than in lowlanders. At any time, indices of muscle oxygenation were not different between groups. Muscle contractile properties in Sherpa, independent of muscle oxygenation, were less perturbed by non-volitional fatigue. Hence, elements within the contractile machinery contribute to the superior physical performance of Sherpa at high altitude. ABSTRACT: Altitude-related acclimatisation is characterised by marked muscular adaptations. Lowlanders and Sherpa differ in their muscular genotypic and phenotypic characteristics, which may influence peripheral fatigability at altitude. After gradual ascent to 5050 m, 12 lowlanders and 10 age-matched Sherpa (32 ± 10 vs. 31 ± 11 years, respectively) underwent three bouts (separated by 15 s rest) of 75 intermittent electrically-evoked contractions (12 pulses at 15 Hz, 1.6 s between train onsets) of the dominant leg quadriceps, at the intensity which initially evoked 30% of maximal voluntary force. Trains were also delivered at minutes 1, 2 and 3 after the protocol to measure recovery. Tissue oxygenation index (TOI) and total haemoglobin (tHb) were quantified by a near-infrared spectroscopy probe secured over rectus femoris. Superficial femoral artery blood flow was recorded using ultrasonography, and delivery of oxygen was estimated (eDO2 ). At the end of bout 1, peak force was greater in Sherpa than in lowlanders (91.5% vs. 84.5% baseline, respectively; P < 0.05). Peak rate of force development (pRFD), the first 200 ms of the contractile impulse (CI200 ), and half-relaxation time (HRT) recovered faster in Sherpa than in lowlanders (percentage of baseline at 1 min: pRFD: 89% vs. 74%; CI200 : 91% vs. 80%; HRT: 113% vs. 123%, respectively; P < 0.05). Vascular measures were pooled for lowlanders and Sherpa as they did not differ during fatigue or recovery (P < 0.05). Mid bout 3, TOI was decreased (90% baseline) whereas tHb was increased (109% baseline). After bout 3, eDO2 was markedly increased (1266% baseline). The skeletal muscle of Sherpa seemingly favours repeated force production at altitude for similar oxygen delivery compared to lowlanders.
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Aclimatación/fisiología , Altitud , Expediciones , Fatiga , Músculo Esquelético/fisiopatología , Adulto , Humanos , Hipoxia/fisiopatología , Masculino , Contracción Muscular , Nepal , Adulto JovenRESUMEN
NEW FINDINGS: What is the central question of the study? Does the use of antioxidants alter cerebrovascular function and blood flow at sea level (344 m) and/or high altitude (5050 m)? What is the main finding and its importance? This is the first study to investigate whether antioxidant administration alters cerebrovascular regulation and blood flow in response to hypercapnia, acute hypoxia and chronic hypoxia in healthy humans. We demonstrate that an acute dose of antioxidants does not alter cerebrovascular function and blood flow at sea level (344 m) or after 12 days at high altitude (5050 m). ABSTRACT: Hypoxia is associated with an increase in systemic and cerebral formation of free radicals and associated reactants that may be linked to impaired cerebral vascular function and neurological sequelae. To what extent oral antioxidant prophylaxis impacts cerebrovascular function in humans throughout the course of acclimatization to the hypoxia of terrestrial high altitude has not been examined. Thus, the purpose of the present study was to examine the influence of orally ingested antioxidants at clinically relevant doses (vitamins C and E and α-lipoic acid) on cerebrovascular regulation at sea level (344 m; n = 12; female n = 2 participants) and at high altitude (5050 m; n = 9; female n = 2) in a randomized, placebo-controlled and double-blinded crossover design. Hypercapnic and hypoxic cerebrovascular reactivity tests of the internal carotid artery (ICA) were conducted at sea level, and global and regional cerebral blood flow (CBF; i.e. ICA and vertebral artery) were assessed 10-12 days after arrival at 5050 m. At sea level, acute administration of antioxidants did not alter cerebral hypoxic cerebrovascular reactivity (pre versus post: 1.5 ± 0.7 versus 1.2 ± 0.8%∆CBF/-%∆SpO2; P = 0.96) or cerebral hypercapnic cerebrovascular reactivity (pre versus post: 5.7 ± 2.0 versus 5.8 ± 1.9%∆CBF/∆mmHg; P = 0.33). Furthermore, global CBF (P = 0.43) and cerebral vascular conductance (ICA P = 0.08; vertebral artery P = 0.32) were unaltered at 5050 m after antioxidant administration. In conclusion, these data show that an oral antioxidant cocktail known to attenuate systemic oxidative stress failed to alter cerebrovascular function at sea level and CBF during acclimatization to high altitude.
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Antioxidantes/administración & dosificación , Encéfalo/efectos de los fármacos , Hipoxia/tratamiento farmacológico , Hipoxia/fisiopatología , Aclimatación/efectos de los fármacos , Aclimatación/fisiología , Adulto , Altitud , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Velocidad del Flujo Sanguíneo/fisiología , Encéfalo/fisiopatología , Arteria Carótida Interna/efectos de los fármacos , Arteria Carótida Interna/fisiopatología , Circulación Cerebrovascular/efectos de los fármacos , Circulación Cerebrovascular/fisiología , Estudios Cruzados , Método Doble Ciego , Expediciones , Femenino , Humanos , Hipercapnia/tratamiento farmacológico , Hipercapnia/fisiopatología , Masculino , Nepal , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Arteria Vertebral/efectos de los fármacos , Arteria Vertebral/fisiopatología , Adulto JovenRESUMEN
Antibiotics are widely used in pig farming across the world which has led to concerns about the potential impact on human health through the selection of antibiotic resistant pathogenic bacteria. This worry has resulted in the development of a production scheme known as pigs Raised Without Antibiotics (RWA), in which pigs are produced in commercial farms, but are ear-tagged as RWA until slaughter unless they receive treatment, thus allowing the farmer to sell the pigs either as premium priced RWA or as conventional meat. Development of antibiotic resistance in pig farming has been studied in national surveys of antibiotic usage and resistance, as well as in experimental studies of groups of pigs, but not in individual pigs followed longitudinally in a commercial pig farm. In this study, a cohort of RWA designated pigs were sampled at 10 time points from birth until slaughter along with pen-mates treated with antibiotics at the same farm. From these samples, the microbiome, determined using 16S sequencing, and the resistome, as determined using qPCR for 82 resistance genes, was investigated, allowing us to examine the difference between RWA pigs and antibiotic treated pigs. We furthermore included 176 additional pigs from six different RWA farms which were sampled at the slaughterhouse as an endpoint to substantiate the cohort as well as for evaluation of intra-farm variability. The results showed a clear effect of age in both the microbiome and resistome composition from early life up until slaughter. As a function of antibiotic treatment, however, we observed a small but significant divergence between treated and untreated animals in their microbiome composition immediately following treatment, which disappeared before 8 weeks of age. The effect on the resistome was evident and an effect of treatment could still be detected at week 8. In animals sampled at the slaughterhouse, we observed no difference in the microbiome or the resistome as a result of treatment status but did see a strong effect of farm origin. Network analysis of co-occurrence of microbiome and resistome data suggested that some resistance genes may be transferred through mobile genetic elements, so we used Hi-C metagenomics on a subset of samples to investigate this. We conclude that antibiotic treatment has a differential effect on the microbiome vs. the resistome and that although resistance gene load is increased by antibiotic treatment load, this effect disappears before slaughter. More studies are needed to elucidate the optimal way to rear pigs without antibiotics.
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BACKGROUND: The American College of Surgeons National Surgical Quality Improvement Program-Pediatric (ACS-NSQIP-P) database monitors quality outcomes in pediatric surgery. However, the registry might underreport low-volume procedures. This review describes complications after laryngotracheal reconstruction (LTR) based on ACS-NSQIP-P reporting standards. METHODS: A case series with chart review at a tertiary children's hospital included consecutive LTR procedures between 2010 and 2018. Surgical procedures were grouped into single- or double-stage for comparison of thirty-day complication rates. RESULTS: Eighty-four procedures were reviewed with 70% (59/84) double-stage and 30% (25/84) single-stage. Children requiring double-stage procedures were younger (3.3 vs. 6.0 years, P = .002) and more often Black or African American (51% vs. 24%, P = .03). Double-stage LTR was frequently performed on children with grade 3 or 4 subglottic stenosis (90% vs. 52%, P < 001), with a tracheostomy (97% vs. 68%, P = .001) and with gastroesophageal reflux disease (93% vs. 67%, P = .004). Airway-related complications occurred in 19% (16/84) of children and non-airway complications occurred in 16% (13/84) with similar rates between groups. Unplanned reintubation (20% vs. 0%, P = .002), ventilator support longer than 48 hours (12% vs. 0%, P = .02), and total hospitalization lengths (15.6 vs. 6.5 days, P < .001) were increased after single-stage LTR. Children with non-airway complications had more central nervous system disorders (46% vs. 10%, P = .004). CONCLUSION: Postoperative complications after pediatric LTR occur in nearly 20% of children and single-stage procedures have higher unplanned reintubations, prolonged ventilator support and hospitalization lengths. Surgeons should recognize that these typically minor events should be consistently monitored and reported after surgical expansion of the pediatric airway. LEVEL OF EVIDENCE: IV.
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Laringoestenosis , Especialidades Quirúrgicas , Niño , Humanos , Laringoestenosis/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Mejoramiento de la Calidad , Estudios Retrospectivos , Traqueostomía/efectos adversos , Resultado del TratamientoRESUMEN
Purpose: To develop a method to determine the volume of peripapillary hyperreflective ovoid masslike structures (PHOMS) and to examine the correlation between PHOMS and anatomic optic nerve head characteristics in a large cohort of patients with optic disc drusen (ODD). Design: Retrospective, observational study of patients with ODD. Participants: Patients with ODD seen in a 3-year period. Methods: We determined the prevalence of PHOMS. We then developed a method to calculate the volume of PHOMS and measured this in all patients where radial scans on OCT were available. We analyzed the correlation between PHOMS volume and patient age, size of Bruch's membrane opening (BMO), ODD visibility, and anatomic location of ODD in the optic nerve. Main Outcome Measures: Prevalence and characteristics of PHOMS in patients with ODD. Results: In 247 (77%) eyes with ODD, PHOMS were found. Among these, 80% were in the first decade of life, 87% were in the second decade, 89% were in the third decade, 85% were in the fourth decade, 74% were in the fifth decade, 73% were in the sixth decade, 58% were in the seventh decade, 40% were in the eighth decade, and 0% were in the ninth decade. The ophthalmoscopic visibility of ODD increased with age. The volume of PHOMS decreased with age, but with no correlation to the size of BMO. The median volume of PHOMS was 0.27 mm3 (interquartile range [IQR], 0.13-0.49 mm3). Predominantly, PHOMS were observed in the nasal peripapillary area (87.5% nasal, 78.5% superior, 67% inferior, and 63.5% temporal). Conclusions: In patients with ODD, PHOMS are seen frequently, with the highest prevalence in younger individuals. The volume of PHOMS decreases with age, and PHOMS are seen more frequently in patients with superficial ODD.
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High entropy alloy (HEA) nanoparticles hold promise in heterogeneous catalysis, and recently, simple and benign solvothermal synthesis was achieved for the equimolar PtIrPdRhRu. Here we experimentally explore the available composition space in this system, and we find that single-phase products can be obtained at significant deviations from the equimolar case.
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Passive hot water immersion (PHWI) provides a peripheral vasculature shear stimulus comparable to low-intensity exercise within the active skeletal muscle, whereas moderate- and high-intensity exercise elicit substantially greater shear rates in the peripheral vasculature, likely conferring greater vascular benefits. Notably, few studies have compared postintervention shear rates in the peripheral and cerebral vasculature after high-intensity exercise and PHWI, especially considering that the postintervention recovery period represents a key window in which adaptation occurs. Therefore, we aimed to compare shear rates in the internal carotid artery (ICA), vertebral artery (VA), and common femoral artery (CFA) between high-intensity exercise and whole body PHWI for up to 80 min after intervention. Fifteen healthy (27 ± 4 yr), moderately trained individuals underwent three time-matched interventions in a randomized order that included 30 min of whole body immersion in a 42°C hot bath, 30 min of treadmill running and 5 × 4-min high-intensity intervals (HIIE). There were no differences in ICA (P = 0.4643) and VA (P = 0.1940) shear rates between PHWI and exercise (both continuous and HIIE) after intervention. All three interventions elicited comparable increases in CFA shear rate after intervention (P = 0.0671); however, CFA shear rate was slightly higher 40 min after threshold running (P = 0.0464) and slightly higher, although not statistically, for HIIE (P = 0.0565) compared with PHWI. Our results suggest that time- and core temperature-matched high-intensity exercise and PHWI elicit limited changes in cerebral shear and comparable increases in peripheral vasculature shear rates when measured for up to 80 min after intervention.NEW & NOTEWORTHY The study aimed to compare shear rates in lower limb and extracranial cerebral blood vessels for up to 80 min after high-intensity exercise and whole body passive hot water immersion (PHWI). Time- and core temperature-matched high-intensity exercise and whole body PHWI both elicited minimal, but comparable, postintervention changes in cerebral artery shear rate. Furthermore, 30 min of PHWI caused a postintervention increase in femoral shear rate similar to high-intensity exercise; however, femoral shear remained slightly elevated for a longer period after high-intensity exercise. These results suggest that PHWI provides postintervention changes in lower limb peripheral shear rates comparable to intense exercise and is likely a therapeutic alternative in individuals unable to perform exercise.
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Ejercicio Físico , Inmersión , Arterias Cerebrales , Humanos , Músculo Esquelético , AguaRESUMEN
Polonium-210 (210Po) is a radionuclide sentinel as it bioaccumulates in marine organisms, thereby being the main contributor to committed dietary doses in seafood consumers. Although seafood and marine mammals are an important part of the traditional Inuit diet, there is a general lack of information on the 210Po concentrations in the Greenlandic marine food chain leading to the human consumer. Here, we determine background 210Po concentrations in edible parts of different marine organisms from Greenland and provide a dose assessment. Blue mussels (Mytilus edulis), organs of ringed seal (Pusa hispida) and polar bear (Ursus maritimus) displayed significantly elevated 210Po concentrations in respect to all other studied organisms (p < 0.001). 210Po concentrations ranged from 0.02 Bq kg-1, w.w. in Greenland halibut (Reinhardtius hippoglossoides) muscle to 78 Bq kg-1, w.w. and 202 Bq kg-1, w.w. in ringed seal muscle and kidneys, respectively. 210Po concentration ratio for edible parts increases in the order bladderwrack (Fucus Vesiculosus), northern shrimp (Pandalus borealis), blue mussels, and from fish species to ringed seal and polar bear. 210Po distribution in fish, ringed seal, and polar bear follows a general pattern, the lowest concentrations were in muscle, and the highest concentrations were in the organs involved in metabolism. The derived 210Po annual absorbed dose in edible parts of studied marine organisms are several orders of magnitude lower than the recommended dose rate screening value of 10 µGy h-1. Effective doses from intake of 210Po to Greenland average children (1.4 mSv y-1), and high seafood and marine mammal consumers (2 mSv y-1 for adults and 3.6 mSv y-1 for children) are higher than the world average annual effective dose due to ingestion of naturally occurring radionuclides.
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Polonio , Contaminantes Radiactivos del Agua , Animales , Biota , Groenlandia , Humanos , Polonio/análisis , Contaminantes Radiactivos del Agua/análisisRESUMEN
Passive heating has emerged as a therapeutic intervention for the treatment and prevention of cardiovascular disease. Like exercise, heating increases peripheral artery blood flow and shear rate, which is thought to be a primary mechanism underpinning endothelium-mediated vascular adaptation. However, few studies have compared the increase in arterial blood flow and shear rate between dynamic exercise and passive heating. In a fixed crossover design study, 15 moderately trained healthy participants (25.6 ± 3.4 yr) (5 female) underwent 30 min of whole body passive heating (42°C bath), followed on a separate day by 30 min of semi-recumbent stepping exercise performed at two workloads corresponding to the increase in cardiac output (Qc) (Δ3.72 L·min-1) and heart rate (HR) (Δ40 beats/min) recorded at the end of passive heating. At the same Qc (Δ3.72 L·min-1 vs. 3.78 L·min-1), femoral artery blood flow (1,599 mL/min vs. 1,947 mL/min) (P = 0.596) and shear rate (162 s-1 vs. 192 s-1) (P = 0.471) measured by ultrasonography were similar between passive heating and stepping exercise. However, for the same HRMATCHED intensity, femoral blood flow (1,599 mL·min-1 vs. 2,588 mL·min-1) and shear rate (161 s-1 vs. 271 s-1) were significantly greater during exercise, compared with heating (both P = <0.001). The results indicate that, for moderately trained individuals, passive heating increases common femoral artery blood flow and shear rate similar to low-intensity continuous dynamic exercise (29% VÌo2max); however, exercise performed at a higher intensity (53% VÌo2max) results in significantly larger shear rates toward the active skeletal muscle.NEW & NOTEWORTHY Passive heating and exercise increase blood flow through arteries, generating a frictional force, termed shear rate, which is associated with positive vascular health. Few studies have compared the increase in arterial blood flow and shear rate elicited by passive heating with that elicited by dynamic continuous exercise. We found that 30 min of whole body passive hot-water immersion (42°C bath) increased femoral artery blood flow and shear rate equivalent to exercising at a moderate intensity (â¼57% HRmax).
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Ejercicio Físico , Calefacción , Adulto , Femenino , Arteria Femoral , Frecuencia Cardíaca , Hemodinámica , Humanos , Masculino , Flujo Sanguíneo Regional , Adulto JovenRESUMEN
Spaceflight-associated neuro-ocular syndrome (SANS) involves unilateral or bilateral optic disc edema, widening of the optic nerve sheath, and posterior globe flattening. Owing to posterior globe flattening, it is hypothesized that microgravity causes a disproportionate change in intracranial pressure (ICP) relative to intraocular pressure. Countermeasures capable of reducing ICP include thigh cuffs and breathing against inspiratory resistance. Owing to the coupling of central venous pressure (CVP) and intracranial pressure, we hypothesized that both ICP and CVP will be reduced during both countermeasures. In four male participants (32 ± 13 yr) who were previously implanted with Ommaya reservoirs for treatment of unrelated clinical conditions, ICP was measured invasively through these ports. Subjects were healthy at the time of testing. CVP was measured invasively by a peripherally inserted central catheter. Participants breathed through an impedance threshold device (ITD, -7 cmH2O) to generate negative intrathoracic pressure for 5 min, and subsequently, wore bilateral thigh cuffs inflated to 30 mmHg for 2 min. Breathing through an ITD reduced both CVP (6 ± 2 vs. 3 ± 1 mmHg; P = 0.02) and ICP (16 ± 3 vs. 12 ± 1 mmHg; P = 0.04) compared to baseline, a result that was not observed during the free breathing condition (CVP, 6 ± 2 vs. 6 ± 2 mmHg, P = 0.87; ICP, 15 ± 3 vs. 15 ± 4 mmHg, P = 0.68). Inflation of the thigh cuffs to 30 mmHg caused no meaningful reduction in CVP in all four individuals (5 ± 4 vs. 5 ± 4 mmHg; P = 0.1), coincident with minimal reduction in ICP (15 ± 3 vs. 14 ± 4 mmHg; P = 0.13). The application of inspiratory resistance breathing resulted in reductions in both ICP and CVP, likely due to intrathoracic unloading.NEW & NOTEWORTHY Spaceflight causes pathological changes in the eye that may be due to the absence of gravitational unloading of intracranial pressure (ICP) under microgravity conditions commonly referred to as spaceflight-associated neuro-ocular syndrome (SANS), whereby countermeasures aimed at lowering ICP are necessary. These data show that impedance threshold breathing acutely reduces ICP via a reduction in central venous pressure (CVP). Whereas, acute thigh cuff inflation, a popular known spaceflight-associated countermeasure, had little effect on ICP and CVP.