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Objective: Syncope is sudden transient loss of consciousness and postural tone with spontaneous recovery; the most common form is vasovagal syncope (VVS). We previously demonstrated impaired post-synaptic adrenergic responsiveness in young VVS patients was reversed by blocking nitric oxide synthase (NOS). We hypothesised that nitric oxide may account for reduced orthostatic tolerance in young recurrent VVS patients., Methods: We recorded haemodynamics in supine VVS and healthy volunteers (aged 15-27 years), challenged with graded lower body negative pressure (LBNP) (-15, -30, -45 mm Hg each for 5 min, then -60 mm Hg for a maximum of 50 min) with and without NOS inhibitor N G -monomethyl-L-arginine acetate (L-NMMA). Saline plus phenylephrine (Saline+PE) was used as volume and pressor control for L-NMMA., Results: Controls endured 25.9±4.0 min of LBNP during Saline+PE compared with 11.6±1.4 min for fainters (p<0.001). After L-NMMA, control subjects endured 24.8±3.2 min compared with 22.6±1.6 min for fainters. Mean arterial pressure decreased more in VVS patients during LBNP with Saline+PE (p<0.001) which was reversed by L-NMMA; cardiac output decreased similarly in controls and VVS patients and was unaffected by L-NMMA. Total peripheral resistance increased for controls but decreased for VVS during Saline+PE (p<0.001) but was similar following L-NMMA. Splanchnic vascular resistance increased during LBNP in controls, but decreased in VVS patients following Saline+PE which L-NMMA restored., Conclusions: We conclude that arterial vasoconstriction is impaired in young VVS patients, which is corrected by NOS inhibition. The data suggest that both pre- and post-synaptic arterial vasoconstriction may be affected by nitric oxide., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Sympathetic circulatory control is key to the rapid cardiovascular adjustments that occur within seconds of standing upright (orthostasis) and which are required for bipedal stance. Indeed, patients with ineffective sympathetic adrenergic vasoconstriction rapidly develop orthostatic hypotension, prohibiting effective upright activities. One speaks of orthostatic intolerance (OI) when signs, such as hypotension, and symptoms, such as lightheadedness, occur when upright and are relieved by recumbence. The experience of transient mild OI is part of daily life. However, many people experience episodic acute OI as postural faint or chronic OI in the form of orthostatic tachycardia and orthostatic hypotension that significantly reduce the quality of life. Potential mechanisms for OI are discussed including forms of sympathetic hypofunction, forms of sympathetic hyperfunction, and OI that results from regional blood volume redistribution attributable to regional adrenergic hypofunction.

Low flow postural tachycardia syndrome (LFP) is associated with vasoconstriction, reduced cardiac output, increased plasma angiotensin II, reduced bioavailable nitric oxide (NO), and oxidative stress. We tested whether ascorbate would improve cutaneous NO and reduce vasoconstriction when delivered systemically. We used local cutaneous heating to 42°C and laser Doppler flowmetry to assess NO-dependent conductance (%CVC(max)) to sodium ascorbate and the systemic hemodynamic response to ascorbic acid in 11 LFP patients and in 8 control subjects (aged 23 ± 2 yr). We perfused intradermal microdialysis catheters with sodium ascorbate (10 mM) or Ringer solution. Predrug heat response was reduced in LFP, particularly the NO-dependent plateau phase (56 ± 6 vs. 88 ± 7%CVC(max)). Ascorbate increased baseline skin flow in LFP and control subjects and increased the LFP plateau response (82 ± 6 vs. 92 ± 6 control). Systemic infusion experiments used Finometer and ModelFlow to estimate relative cardiac index (CI) and forearm and calf venous occlusion plethysmography to estimate blood flows, peripheral arterial and venous resistances, and capacitance before and after infusing ascorbic acid. CI increased 40% after ascorbate as did peripheral flows. Peripheral resistances were increased (nearly double control) and decreased by nearly 50% after ascorbate. Calf capacitance and venous resistance were decreased compared with control but normalized with ascorbate. These data provide experimental support for the concept that oxidative stress and reduced NO possibly contribute to vasoconstriction and venoconstriction of LFP.

Our prior studies indicated that postural fainting relates to thoracic hypovolemia. A supranormal increase in initial vascular resistance was sustained by increased peripheral resistance until late during head-up tilt (HUT), whereas splanchnic resistance, cardiac output, and blood pressure (BP) decreased throughout HUT. Our aim in the present study was to investigate the alterations of baroreflex activity that occur in synchrony with the beat-to-beat time-dependent changes in heart rate (HR), BP, and total peripheral resistance (TPR). We proposed that changes of low-frequency Mayer waves reflect sympathetic baroreflex. We used DWT multiresolution analyses to measure their time dependence. We studied 22 patients, 13 to 21 yr old, 14 who fainted within 10 min of upright tilt (fainters) and 8 healthy control subjects. Multiresolution analysis was obtained of continuous BP, HR, and respirations as a function of time during 70 degrees upright tilt at different scales corresponding to frequency bands. Wavelet power was concentrated in scales corresponding to 0.125 and 0.25 Hz. A major difference from control subjects was observed in fainters at the 0.125 Hz AP scale, which progressively decreased from early HUT. The alpha index at 0.125 Hz was increased in fainters. RR interval 0.25 Hz power decreased in fainters and controls but was markedly increased in fainters with syncope and thereafter corresponding to increased vagal tone compared with control subjects at those times only. The data imply a rapid reduction in time-dependent sympathetic baroreflex activity in fainters but not control subjects during HUT.

Transient orthostatic hypotension is a common experience of many healthy adolescents and is the expected outcome of relatively dilated-dependent vascular tone. These children may experience brief symptoms of orthostatic intolerance when standing up rapidly, but they have no chronic symptoms or diseases. However, persistent orthostatic hypotension and chronic symptoms of orthostatic intolerance indicate postural tachycardia syndrome.

The Valsalva maneuver is frequently used to test autonomic function. Previous work demonstrated that the blood pressure decrease during the Valsalva maneuver relates to thoracic hypovolemia, which may preclude pressure recovery during phase II, even with normal resting peripheral vasoconstriction. We hypothesized that increased regional blood volume, specifically splanchnic hypervolemia, accounts for the degree of thoracic hypovolemia during the Valsalva maneuver. We studied 17 healthy volunteers aged 15-22 yr. All had normal blood volumes by dye dilution. Subjects also had normal vascular resistance while supine as well as normal vasoconstrictor responses during 35[degrees] upright tilt. We assessed changes in estimated splanchnic, pelvic-thigh, and lower leg blood volume, along with thoracic blood volume shifts, by impedance plethysmography before and during the Valsalva maneuver performed in the supine position. Early increases in splanchnic blood volume dominated the regional vascular changes during the Valsalva maneuver. The increase in splanchnic blood volume correlated well ([r.sup.2] = 0.65, P < 0.00001) with the decrease in thoracic blood volume, there was less correlation of the increase in pelvic blood volume ([r.sup.2] = 0.21, P < 0.03), and there was no correlation of the increase in leg blood volume ([r.sup.2] = 0.001, P = 0.9). There was no relation of thoracic hypovolemia with blood volume or peripheral resistance in supine or upright positions. Thoracic hypovolemia during the Valsalva maneuver is closely related to splanchnic hyperemia and weakly related to regional changes in blood volume elsewhere. Changes in baseline splanchnic vascular properties may account for variability in thoracic blood volume changes during the Valsalva maneuver. vasoconstriction; veins; capacitance; mesenteric; autonomic

Head-up tilt test (TT) has been used for >50 years to study heart rate/blood pressure adaptation to positional changes, to model responses to haemorrhage, to assess orthostatic hypotension, and to evaluate haemodynamic and neuroendocrine responses in congestive heart failure, autonomic dysfunction, and hypertension. During these studies, some subjects experienced syncope due to vasovagal reflex. As a result, tilt testing was incorporated into clinical assessment of syncope when the origin was unknown. Subsequently, clinical experience supports the diagnostic value of TT. This is highlighted in evidence-based professional practice guidelines, which provide advice for TT methodology and interpretation, while concurrently identifying its limitations. Thus, TT remains a valuable clinical asset, one that has added importantly to the appreciation of pathophysiology of syncope/collapse and, thereby, has improved care of syncopal patients. [ABSTRACT FROM AUTHOR]

Upright hyperventilation occurs in ~25% of our patients with postural tachycardia syndrome (POTS). Poikilocapnic hyperventilation alone causes tachycardia. Here, we examined changes in respiration and hemodynamics comprising cardiac output (CO), systemic vascular resistance (SVR), and blood pressure (BP) measured during head-up tilt (HUT) in three groups: patients with POTS and hyperventilation (POTS-HV), patients with panic disorder who hyperventilate (Panic), and healthy controls performing voluntary upright hyperpnea (Voluntary-HV). Though all were comparably tachycardic during hyperventilation, POTS-HV manifested hyperpnea, decreased CO, increased SVR, and increased BP during HUT; Panic patients showed both hyperpnea and tachypnea, increased CO, and increased SVR as BP increased during HUT; and Voluntary-HV were hyperpneic by design and had increased CO, decreased SVR, and decreased BP during upright hyperventilation. Mechanisms of hyperventilation and hemodynamic changes differed among POTS-HV, Panic, and Voluntary- HV subjects. We hypothesize that the hyperventilation in POTS is caused by a mechanism involving peripheral chemoreflex sensitization by intermittent ischemic hypoxia. NEW & NOTEWORTHY Hyperventilation is common in postural tachycardia syndrome (POTS) and has distinctive cardiovascular characteristics when compared with hyperventilation in panic disorder or with voluntary hyperventilation. Hyperventilation in POTS is hyperpnea only, distinct from panic in which tachypnea also occurs. Cardiac output is decreased in POTS, whereas peripheral resistance and blood pressure (BP) are increased. This is distinct from voluntary hyperventilation where cardiac output is increased and resistance and BP are decreased and from panic where they are all increased. [ABSTRACT FROM AUTHOR]

Introduction The aim of this paper is to describe and demonstrate how a new bioimpedance analytical procedure can be used to monitor cellular hydration of End Stage Renal Disease (ESRD) patients during hemodialysis (HD). Methods A tetra-polar bioimpedance spectroscope (BIS), (UFI Inc., Morro Bay, CA), was used to measure the tissue resistance and reactance of the calf of 17 ESRD patients at 40 discrete frequencies once a minute during dialysis treatment. These measurements were then used to derive intracellular, interstitial, and intravascular compartment volume changes during dialysis. Findings The mean (± SD) extracellular resistance increased during dialysis from 92.4 ± 3.5 to 117.7 ± 5.8 Ohms. While the mean intracellular resistance decreased from 413.5 ± 11.7 to 348.5 ± 8.2 Ohms. It was calculated from these data that the mean intravascular volume fell 9.5%; interstitial volume fell 33.4%; and intracellular volume gained 20.3%. Discussion These results suggest that an extensive fluid shift into the cells may take place during HD. The present research may contribute to a better understanding of how factors that influence fluid redistribution may affect an ESRD patient during dialysis. In light of this finding, it is concluded that the rate of vascular refill is jointly determined with the rate of 'cellular refill' and the transfer of fluid from the intertitial compartment into the intravascular space. [ABSTRACT FROM AUTHOR]

We used breath-holding during inspiration as a model to study the effect of pulmonary stretch on sympathetic nerve activity. Twelve healthy subjects (7 females, 5 males; 19–27 years) were tested while they performed an inspiratory breath-hold, both supine and during a 60° head-up tilt (HUT 60). Heart rate (HR), mean arterial blood pressure (MAP), respiration, muscle sympathetic nerve activity (MSNA), oxygen saturation (SaO2) and end tidal carbon dioxide (ETCO2) were recorded. Cardiac output (CO) and total peripheral resistance (TPR) were calculated. While breath-holding, ETCO2 increased significantly from 41 ± 2 to 60 ± 2 Torr during supine ( p < 0.05) and 38 ± 2 Torr to 58 ± 2 during HUT60 ( p < 0.05); SaO2 decreased from 98 ± 1.5% to 95 ± 1.4% supine, and from 97 ± 1.5% to 94 ± 1.7% during HUT60 ( p = NS). MSNA showed three distinctive phases, a quiescent phase due to pulmonary stretch associated with decreased MAP, HR, CO, and TPR; a second phase of baroreflex-mediated elevated MSNA which was associated with recovery of MAP and HR only during HUT60; CO and peripheral resistance returned to baseline while supine and HUT60; a third phase of further increased MSNA activity related to hypercapnia and associated with increased TPR. Breath-holding results in initial reductions of MSNA, MAP, and HR by the pulmonary stretch reflex followed by increased sympathetic activity related to the arterial baroreflex and chemoreflex. [ABSTRACT FROM AUTHOR]

Postural tachycardia syndrome (POTS) is characterized by exercise intolerance and sympathoactivation. To examine whether abnormal cardiac output and central blood volume changes occur during exercise in POTS, we studied 29 patients with POTS (17-29 yr) and 12 healthy subjects (18-27 yr) using impedance and venous occlusion plethysmography to assess regional blood volumes and flows during supine static handgrip to evoke the exercise pressor reflex. POTS was subgrouped into normal and low-flow groups based on calf blood flow. We examined autonomic effects with variability techniques. During handgrip, systolic blood pressure increased from 112 ± 4 to 139 ± 9 mmHg in control, from 119 ± 6 to 143 ± 9 in normal-flow POTS, but only from 117 ± 4 to 128 ± 6 in low-flow POTS. Heart rate increased from 63 ± 6 to 82 ± 4 beats/mm in control, 76 ± 3 to 92 ± 6 beats/mm in normal-flow POTS, and 88 ± 4 to 100 ± 6 beats/mm in low-flow POTS. Heart rate variability and coherence markedly decreased in low-flow POTS, indicating uncoupling of baroreflex heart rate regulation. The increase in central blood volume with handgrip was absent in low-flow POTS and blunted in normal-flow POTS associated with abnormal splanchnic emptying. Cardiac output increased in control, was unchanged in low-flow POTS, and was attenuated in normal-flow POTS. Total peripheral resistance was increased compared with control in all POTS. The exercise pressor reflex was attenuated in low-flow POTS. While increased cardiac output and central blood volume characterizes controls, increased peripheral resistance with blunted or eliminated in central blood volume increments characterizes POTS and may contribute to exercise intolerance. [ABSTRACT FROM AUTHOR]

Recent studies have indicated that plantar-based vibration may be an effective approach for the prevention and treatment of osteoporosis. We addressed the hypothesis of whether the plantar vibration, operated by way of the skeletal muscle pump, resulting in enhanced blood and fluid flow to the lower body. We combined plantar stimulation with upright tilt table testing in 18 women aged 46-63 yr. We used strain-gauge plethysmography to measure calf blood flow, venous capacitance, and the microvascular filtration relation, as well as impedance plethysmography to examine changes in leg, splanchnic, and thoracic blood flow while supine at a 35° upright tilt. A vibrating platform was placed on the footboard of a tilt table, and measurements were made at 0, 15, and 45 Hz with an amplitude of 0.2 g point to point, presented in random order. Impedance-measured supine blood flows were significantly (P = 0.05) increased in the calf (30%), pelvic (26%), and thoracic regions (20%) by plantar vibration at 45 Hz. Moreover, the 25-35% decreases in calf and pelvic blood flows associated with upright tilt were reversed by plantar vibration, and the decrease in thoracic blood flow was significantly attenuated. Strain-gauge measurements showed an attenuation of upright calf blood flow. In addition, the microvascular filtration relation was shifted with vibration, producing a pronounced increase in the threshold for edema, P1, due to enhanced lymphatic flow. Supine values for P1 increased from 24 ± 2 mmHg at 0 Hz to 27 ± 3 mmHg at 15 Hz, and finally to 31 ± 2 mmHg at 45 Hz (P < 0.01). Upright values for P, increased from 25 ± 3 mmHg at 0 Hz, to 28 ± 4 mmHg at 15 Hz, and finally to 35 ± 4 mmHg at 45 Hz. The results suggest that plantar vibration serves to significantly enhance peripheral and systemic blood flow, peripheral lymphatic flow, and venous drainage, which may account for the apparent ability of such stimuli to influence bone mass. [ABSTRACT FROM AUTHOR]

Variants of postural tachycardia syndrome (POTS) are associated with increased ["high-flow" POTS (HFP)], decreased ["low-flow" POTS (LFP)], and normal ["normal-flow" POTS (NFP)] blood flow measured in the lower extremities while subjects were in the supine position. We propose that postural tachycardia is related to thoracic hypovolemia during orthostasis but that the patterns of peripheral blood flow relate to different mechanisms for thoracic hypovolemia. We studied 37 POTS patients aged 14-21 yr: 14 LFP, 15 NFP, and 8 HFP patients and 12 healthy control subjects. Peripheral blood flow was measured in the supine position by venous occlusion strain-gauge plethysmography of the forearm and calf to subgroup patients. Using indocyanine green techniques, we showed decreased cardiac index (CI) and increased total peripheral resistance (TPR) in LFP, increased CI and decreased TPR in HFP, and unchanged CI and TPR in NFP while subjects were supine compared with control subjects. Blood volume tended to be decreased in LFP compared with control subjects. We used impedance plethysmography to assess regional blood volume redistribution during upright tilt. Thoracic blood volume decreased, whereas splanchnic, pelvic, and leg blood volumes increased, for all subjects during orthostasis but were markedly lower than control for all POTS groups. Splanchnic volume was increased in NFP and LFP. Pelvic blood volume was increased in HFP only. Calf volume was increased above control in HFP and LFP. The results support the hypothesis of (at least) three pathophysiologic variants of POTS distinguished by peripheral blood flow related to characteristic changes in regional circulations. The data demonstrate enhanced thoracic hypovolemia during upright tilt and confirm that POTS is related to inadequate cardiac venous return during orthostasis. [ABSTRACT FROM AUTHOR]

The Valsalva maneuver (VM) is frequently used to test autonomic function. However, the VM is also affected by changes in blood volume and blood volume redistribution. We hypothesized that even a standardized VM may produce a wide range of thoracic blood volume shifts. Larger blood volume shifts in some normovolemic individuals may be sufficient to induce decreases in blood pressure (BP) that preclude autonomic restoration of BP in phase II of the VM. To test this hypothesis, we studied 17 healthy volunteers aged 15-22 yr. All had similar vasoconstrictor responses when supine and upright and normal blood volume measurements. We assessed changes in thoracic blood volume by impedance plethysmography before and during the VM performed while subjects were supine. In some subjects, large decreases in BP were produced by thoracic hypovolemia. The maxi- mum fractional decrease in BP correlated well (r²> = 0.64; P < 0.001) with thoracic hypovolemia and with systolic BP at the end of phase II of the VM (r² = 0.67; P < 0.001). The BP overshoot in phase IV of the VM was uncorrelated to phase II changes, which suggests intact autonomic vasoconstriction. We conclude that the BP decrease during the VM is related to a variable decrease in thoracic blood volume that may be sufficient to preclude pressure recovery during phase II even with normal resting peripheral vasoconstriction. The VM depends on vascular as well as autonomic activation, which broadens its utility but complicates its analysis. [ABSTRACT FROM AUTHOR]

Standing translocates thoracic blood volume into the dependent body. The skeletal muscle pump participates in preventing orthostatic intolerance by enhancing venous return. We investigated the hypothesis that skeletal muscle pump function is impaired in postural tachycardia (POTS) associated with low calf blood flow (low-flow POTS) and depends in general on muscle blood flow. We compared 12 subjects that have low-flow POTS with 10 controls and 7 patients that have POTS and normal calf blood flow using strain-gauge plethysmography to measure peripheral blood flow, venous capacitance, and calf muscle pump function. Blood volume was estimated by dye dilution. We found that calf circumference was reduced in low-flow POTS (32 ± 1 vs. 39 ± 3 and 43 ± 3 cm) and, compared with controls and POTS patients with normal blood flow, is related to the reduced fraction of calf venous capacity emptied during voluntary muscle contraction (ejection fraction, 0.52 ± 0.07 vs. 0.76 ± 0.07 and 0.80 ± 0.06). We found that blood flow was linearly correlated (rp = 0.69) with calf circumference (used as a surrogate for muscle mass). Blood volume measurements were 2.2 ± 0.3 in low-flow POTS vs. 2.6 ± 0.5 in controls (P = 0.17) and 2.4 ± 0.7 in normal-flow POTS patients. Decreased calf blood flow may reduce calf size in POTS and thereby impair the upright ejective ability of the skeletal muscle pump and further contribute to overall reduced blood flow and orthostatic intolerance in these patients. [ABSTRACT FROM AUTHOR]