The Influence of a Total Body Resistance Training Program on Autonomic Modulation and Strength Variables in Young Adults.

The purpose of this study was to examine autonomic modulation using multiple quantitative measures before and after a resistance training (RT) intervention. Seventeen young adults (age 18-35 years) were tested for body composition, muscular strength, and autonomic activity. The RT protocol targeted total-body large muscle groups, which were performed three days a week for eight-weeks. Autonomic assessments included respiratory sinus arrhythmia (RSA), static handgrip exercise, Valsalva maneuver, heart rate variability (HRV), and tilt-table testing. The main finding was that tilt-table duration increased by 68 seconds (p = 0.05) after RT. Upper body strength increased by 11.2 kg (p = 0.001) and lower body strength increased by 68.3 kg (p < 0.001) following completion of the RT intervention. The average total lean mass increased by 1.5 kg (p < 0.01), while total fat mass was unchanged (Δ = 0.5 kg, p = 0.23). RSA (Δ = 0.4, p = 0.89), Valsalva ratio (Δ = -0.09, p = 0.48), static handgrip (Δ = 8 mm Hg, p = 0.07), and HRV (Δ = -0.4, p = 0.53) were not affected by RT. The results from this study suggest that RT improves tilt-table tolerance in a young healthy population as evidence by improved tilt-table duration. However, RT seemed to have no effect on cardio-vagal or adrenergic function.

Head Trauma not Associated with Long Term Effects on Autonomic Function.

Contact-sports can elicit concussions, which impacts autonomic function, as well as elicit repetitive head trauma, where autonomic function has not yet been assessed. The purpose of this study was to determine if differences in autonomic function exist among three groups (CTRL: healthy non-contact-sport participant, RHT: repetitive head trauma contact-sport participant, CONC: previous concussion). Forty participants (16 men and 24 women), aged 18-37 (22 ± 3), participated in the study. Participants were grouped based on their sport and concussion history (CTRL, RHT, and CONC). Body composition was measured via air displacement plethysmography. Prior to testing, participants were outfitted with equipment to evaluate heart rate, blood pressure, and cerebral-artery blood flow velocity (CBFv). The participant performed against three stimuli: deep breathing, Valsalva maneuver, and a 70° head-up tilt test. Following autonomic function testing, a YMCA submaximal cycle test was performed. All group comparisons were analyzed using a one-way ANOVA and all data are presented as means ± standard deviation. The results of this study indicated that the groups did not differ in respiratory sinus arrhythmia (CTRL: 22 ± 6 bpm, RHT: 21 ± 8 bpm, CONC: 19 ± 7 bpm, p = 0.471), Valsalva ratio (CTRL: 2.19 ± 0.39, RHT: 2.09 ± 0.37, CONC: 2.00 ± 0.47, p = 0.519), CBFv (CTRL: 47.74 ± 25.28 cm/s, RHT: 40.99 ± 10.93 cm/s, CONC: 43.97 ± 17.55 cm/s, p = 0.657), or tilt time (CTRL: 806.09 ± 368.37 sec, RHT: 943.07 ± 339.54 sec, CONC: 978.40 ± 387.98 sec, p = 0.479). However, CONC (113.24 ± 11.64 mmHg) had a significantly higher mean systolic blood pressure during the tilt test than CTRL (102.66 ± 7.79 mmHg, p = 0.026), while RHT (107.9 ± 9.0 mmHg) was not significantly different than CTRL (p = 0.39) or CONC (p = 0.319). The results of this study are the first step in determining if long-lasting deficits to the autonomic nervous system occur following a diagnosis of concussion. However, concussions do not seem to have lasting effects on autonomic function. Overwhelmingly, dysautonomia is not present during chronic recovery from concussions or in individuals with RHT from contact-sports. In the future, sex should be considered as a variable.

Effect of Sex and Menstrual Cycle on Skin Sensory Nerve Contribution to Local Heating.

The purpose of this study was to determine sex differences in the contribution of sensory nerves to rapid cutaneous thermal hyperemia. Healthy young females (n = 15, tested during both the early follicular (EF) and the mid-luteal (ML) phase of the menstrual cycle) and males (n = 15) had a 4 cm2 area of skin on one forearm and one leg treated with a eutectic mixture of local anesthetic (EMLA). EMLA sites, along with corresponding control sites, were instrumented with laser Doppler flowmetry probes and local skin heaters. Baseline (33 °C), rapid and sustained vasodilation (42 °C), and maximal vasodilation (44 °C) skin blood flow data were obtained and expressed as a percentage of maximal cutaneous vascular conductance (%CVCmax). Contribution of sensory nerve involvement was determined by comparing the EMLA site to its matched control site utilizing the formula [(% CVCmax control - % CVCmax treatment) / % CVCmax control] × 100. The contribution of sensory nerves to rapid cutaneous thermal hyperemia in the forearm was 24 ± 18 %CVCmax in males, 41 ± 17 %CVCmax in ML females (p = 0.02 vs. males), and 35 ± 17 %CVCmax in EF females (p > 0.05 vs. males). In the leg, the contribution of sensory nerves was 16 ± 15 %CVCmax in males, 34 ± 17 %CVCmax for ML females (p = 0.02 vs. males), and 28 ± 21 %CVCmax in EF females (p > 0.05 vs. males). ML females exhibited a greater contribution of sensory nerves to rapid cutaneous thermal hyperemia in the forearm and leg, possibly attributed to elevated reproductive hormones during the ML phase.

Comparison of Body Composition Prediction Equations with Air Displacement Plethysmography in Overweight and Obese Caucasian Males.

Body mass index (BMI) has been used for years by clinicians to approximate total body fat. However, the body adiposity index (BAI), body adiposity index from the FELS longitudinal study (BAIFELS), and an equation developed by Deurenberg et al. (BFD) were created recently to offset BMI's limitations and accurately estimate percent body fat (%BF). The prevalence of overweight and obese Caucasian men is increasing in the United States; currently, there is no established way to quickly and accurately predict their %BF. PURPOSE: To compare the existing %BF equations (BAI, BAIFELS, and BFD) to measured %BF via air displacement plethysmography (ADP) in order to determine the most accurate way to predict %BF in overweight and obese Caucasian men. METHODS: Four hundred and fifty-two Caucasian men aged from 18 to 76, with a BMI of 25.0 to 42.4 kg/m2, participated in this study. Height, weight, waist circumference, hip circumference, and body composition using ADP were measured on each participant. These measurements were inserted into the three equations to determine any differences between the equations and the actual %BF measured by ADP. RESULTS: Differences in %BF between ADP and the BAI (p < 0.001) and ADP and the BAIFELS (p < 0.001) were discovered. While no differences (p = 1.00) between ADP and BFD existed. CONCLUSION: In a population of overweight and obese Caucasian adults from the United States, the BAI and BAIFELS are not appropriate to predict %BF while the BFD prediction equation proved worthy of consideration.

Postural orthostatic tachycardia syndrome in primary care: diagnosis, treatment and a case of African-American man presenting with POTS.

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous autonomic disorder characterised by orthostatic intolerance and a rise in heart rate by at least 30 bpm or an absolute heart rate value of at least 120 bpm within 10 min of standing or during a tilt table test. Overwhelmingly, POTS affects young Caucasian women, which can lead physicians to miss the diagnosis in men or non-white patients. We describe a case of 29-year-old African-American man who developed lightheadedness, generalised weakness, tachycardia and palpitations and was subsequently diagnosed with POTS. We review its clinical features, differential diagnosis, pathophysiology and treatment options. We also emphasise that POTS should be considered as a differential diagnosis in any patient presenting with typical clinical features, who may not be in the usual demographics of the disorder.

Effect of sympathetic nerve blockade on low-frequency oscillations of forearm and leg skin blood flow in healthy humans.

OBJECTIVE: To Examine the effect of inhibiting sympathetic function on cutaneous vasomotion in the forearm and leg. METHODS: Intradermal microdialysis fibers were placed in the forearm and leg, one as an untreated control (lactated Ringer's) and the other perfused with bretylium tosylate to block sympathetic nerves. Skin blood flow was monitored using laser Doppler flowmetry. Baseline was collected for 10 minutes before local skin temperature was increased to 42°C. Spectral analysis was performed using a Morlet wavelet. RESULTS: Bretylium tosylate increased skin blood flow during baseline in the forearm (d=1.6, P<.05) and leg (d=0.5, P<.05) and decreased skin blood flow at both sites during both the initial peak (d≥1.0, P<.05) and plateau (d≥0.8, P<.05). Treatment with bretylium tosylate reduced wavelet amplitude associated with neural activity during baseline in the forearm (d=1.6, P<.05) and leg (d=0.9, P<.05). This reduction in wavelet amplitude at bretylium tosylate-treated sites was also observed during the initial vasodilation to local heating in both the forearm (d=1.6, P<.05) and leg (d=1.4, P<.05) and during the sustained vasodilation in both the forearm (d=1.6, P<.05) and leg (d=1.2, P<.05). CONCLUSIONS: Our data support that the frequency band (0.021-0.052 Hz) associated with neurogenic activity appears to be correct having a large sympathetic component.

Neuropeptide Y not involved in cutaneous vascular control in young human females taking oral contraceptive hormones.

We previously reported that the cutaneous vasodilator response to local warming in males required noradrenaline (NA) and neuropeptide-Y (NPY). Animal work has shown no role for NPY in female vascular control. We investigated the contribution of NA and NPY in human female cutaneous vascular control. Nine female and nine male participants volunteered. To elucidate whether synthetic oestrogen and progesterone altered cutaneous vascular responses, females were tested in high-hormone (HH) and low-hormone (LH) phases of oral contraceptive pill (OCP). Skin blood flow was assessed by laser-Doppler flowmetry and expressed as cutaneous vascular conductance (CVC). Treatments were: control, combined yohimbine and propranolol (YP), BIBP-3226, and bretylium tosylate (BT). YP and BT increased basal CVC (p<0.05) relative to control sites in both HH and LH phases; though, BIBP-3226 had no effect in either phase (both p>0.05). Males basal CVC was increased at all treated sites compared to control sites (all p<0.05). YP and BT treated sites were higher in HH compared to LH (p<0.05). YP and BT treatment reduced the local warming-induced vasodilatation compared to control sites (p>0.05) in both HH and LH phases; whereas, BIBP-3226 treatment had no effect (p>0.05). In males, the vasodilatation achieved at all treated sites was reduced compared to the untreated control site (p<0.05). Data indicate that NA, not NPY, regulates basal skin blood flow and contributes to the vasodilator response to local warming in young females; however, both NA and NPY play a role in both basal and heat-induced cutaneous responses in males.

The effect of heating rate on the cutaneous vasomotion responses of forearm and leg skin in humans.

We examined skin blood flow (SkBF) and vasomotion in the forearm and leg using laser-Doppler fluxmetry (LDF) and spectral analysis to investigate endothelial, sympathetic, and myogenic activities in response to slow (0.1 °C·10 s(-1)) and fast (0.5 °C·10 s(-1)) local heating. At 33 °C (thermoneutral) endothelial activity was higher in the legs than the forearms (P ≤ 0.02). Fast-heating increased SkBF more than slow heating (P=0.037 forearm; P=0.002 leg). At onset of 42 °C, endothelial (P=0.043 forearm; P=0.48 leg) activity increased in both regions during the fast-heating protocol. Following prolonged heating (42 °C) endothelial activity was higher in both the forearm (P=0.002) and leg (P<0.001) following fast-heating. These results confirm regional differences in the response to local heating and suggest that the greater increase in SkBF in response to fast local heating is initially due to increased endothelial and sympathetic activity. Furthermore, with sustained local skin heating, greater vasodilatation was observed with fast heating compared to slow heating. These data indicate that this difference is due to greater endothelial activity following fast heating compared to slow heating, suggesting that the rate of skin heating may alter the mechanisms contributing to cutaneous vasodilatation.

Oscillatory lower body negative pressure impairs task related functional hyperemia in healthy volunteers.

Neurovascular coupling refers to the link between an increase in neural activity in response to a task and an increase in cerebral blood flow denoted "functional hyperemia." Recent work on postural tachycardia syndrome indicated that increased oscillatory cerebral blood flow velocity (CBFv) was associated with reduced functional hyperemia. We hypothesized that a reduction in functional hyperemia could be causally produced in healthy volunteers by using oscillations in lower body negative pressure (OLBNP) to force oscillations in CBFv. CBFv was measured by transcranial Doppler ultrasound of the left middle cerebral artery. We used passive arm flexion applied during eight periodic 60-s flexion/60-s relaxation epochs to produce 120-s periodic changes in functional hyperemia (at 0.0083 Hz). We used -30 mmHg of OLBNP at 0.03, 0.05, and 0.10 Hz, the range for cerebral autoregulation, and measured spectral power of CBFv at all frequencies. Arm flexion power performed without OLBNP was compared with arm flexion power during OLBNP. OLBNP power performed in isolation was compared with power during OLBNP plus arm flexion. Cerebral flow velocity oscillations at 0.05 Hz reduced and at 0.10 Hz eliminated functional hyperemia, while 0.03 Hz did not reach significance. In contrast, arm flexion reduced OLBNP-induced oscillatory power at all frequencies. The interactions between OLBNP-driven CBFv oscillations and arm flexion-driven CBFv oscillations are reciprocal. Thus induced cerebral blood flow oscillations suppress functional hyperemia, and functional hyperemia suppresses cerebral blood flow oscillations. We conclude that oscillatory cerebral blood flow produces a causal reduction of functional hyperemia.

The contribution of sensory nerves to the onset threshold for cutaneous vasodilatation during gradual local skin heating of the forearm and leg.

During local skin heating, the temporal onset of vasodilatation is delayed in the leg compared to the forearm, and sensory nerve blockade abolishes these differences. However, previous work using rapid skin heating did not allow for determination of sensory nerve influences on temperature thresholds for vasodilatation. Two sites were examined on both the forearm and leg, one control (CTRL), and one treated for sensory nerve blockade (EMLA). Skin blood flux was monitored using laser-Doppler probes, with heaters controlling local skin temperature (Tloc). Tloc was increased from 32-44 °C (+1 °C·10 min(-1)). Stimulus-response curves were constructed by fitting a four-parameter logistic function. EMLA significantly increased Tloc onset in the forearm (CTRL=35.3 ± 0.4 °C; EMLA=36.8 ± 0.7 °C) and leg (CTRL=36.5 ± 0.4 °C; EMLA=38.4 ± 0.5 °C; both P<0.05). At both CTRL and EMLA, Tloc onset was higher in the leg compared to the forearm (both P<0.05). In the forearm, median effective temperature to elicit 50% vasodilatation (ET50) was similar between sites (CTRL=39.7 ± 0.3 °C; EMLA=40.2 ± 0.4 °C; P=0.09); however, in the leg, EMLA significantly increased ET50 (CTRL=40.2 ± 0.3 °C; EMLA=41.0 ± 0.3 °C)(P<0.05). At CTRL sites, no limb difference was observed for ET50 (P=0.06); however, with EMLA, ET50 was significantly higher in the leg (P<0.05). EMLA significantly increased the gain of the slope at the forearm, (CTRL=0.31 ± 0.01%CVCmax·°C(-1); EMLA=0.45 ± 0.07%CVCmax·°C(-1)), and leg (CTRL=0.37 ± 0.05%CVCmax·°C(-1); EMLA=0.54 ± 0.04%CVCmax·°C(-1))(both P<0.05). At CTRL sites, the gain was significantly higher in the leg (P<0.05); however, for EMLA, no significant limb difference existed (P=0.10). These data indicate that the onset of vasodilatation occurs at a lower temperature in the forearm than the legs, and sensory nerves play an important role in both limbs.

The contribution of sensory nerves to cutaneous vasodilatation of the forearm and leg to local skin heating.

PURPOSE: The initial cutaneous vasodilatory response to local skin heating is larger in the forearm than the leg. While the initial vasodilatation of the forearm to local heating is primarily dependent on sensory nerves, their role in the leg is unknown. We compared the contribution of sensory nerves in driving the cutaneous vasodilatory response of the forearm and leg to local heating using local anaesthetic (EMLA) cream. METHOD: In seven participants, two skin sites were selected on both the dorsal forearm and anterolateral calf; one site on each region received EMLA, with the other an untreated control. All sites were controlled at 33 °C and then locally heated to 42 °C with integrated laser-Doppler local heating probes. RESULTS: Cutaneous vascular conductance (CVC) during the initial vasodilatation to local heating was smaller in the leg (47 ± 9% max) compared to the forearm (62 ± 7 % max) (P = 0.012). EMLA reduced the initial vasodilatation at both the leg (27 ± 13 % max) (P = 0.02) and forearm (33 ± 14% max) (P < 0.001). The times to onset of vasodilatation, initial vasodilatory peak, and plateau phase were longer in the leg compared to the forearm (all P < 0.05), and EMLA increased these times in both regions (both P < 0.05). CVC during the plateau phase to sustained local skin heating was higher in the leg compared to the forearm at both the untreated (93 ± 6 vs. 85 ± 4% max) (P = 0.33) and EMLA-treated (94 ± 5 vs. 86 ± 6% max) (P = 0.001) sites; EMLA did not affect CVC (P > 0.05). CONCLUSION: The differences in the initial vasodilatory peak to local skin heating between the forearm and the leg are due to the contribution of sensory nerves.

Comparison of the noradrenergic sympathetic nerve contribution during local skin heating at forearm and leg sites in humans.

PURPOSE: We investigated the role of noradrenergic sympathetic nerves in the cutaneous circulation at rest and in response to local heating. METHODS: Dorsal forearm and lateral leg sites were each instrumented with 2 microdialysis fibers, 2 local skin heaters, and 2 laser-Doppler probes. All sites were heated from 33° to 42 °C. Each limb had 1 skin site treated with bretylium tosylate (BT) to block noradrenergic sympathetic neurotransmitter release and 1 site infused with lactated Ringer's (Control). RESULTS: During baseline (33 °C), cutaneous vascular conductance (CVC; laser-Doppler flux/blood pressure) at control (24 ± 2 %max) and BT-treated (29 ± 4 %max) sites in the leg was significantly higher than the forearm (control: 12 ± 1 %max; BT-treated: 17 ± 2 %max) (P = 0.032 and P = 0.042). At 42 °C local skin temperature, the initial peak CVC response with BT decreased compared to control at both forearm (62 ± 3 vs. 86 ± 6 %max, P < 0.01) and leg (67 ± 3 vs. 77 ± 2 %max, P = 0.035) sites. CVC at the forearm with BT was lower than that of the leg (P = 0.02). With control, plateau phase (~35 min at 42 °C) CVC was greater in the leg (98 ± 2 %max) than the forearm (89 ± 4 %max) (P = 0.027). BT reduced the peak CVC in the leg (90 ± 4 %max, P = 0.027) and in the forearm (69 ± 5 %max, P < 0.01). CVC at the BT-treated sites was reduced more in the forearm than in the legs (P < 0.01). CONCLUSIONS: The contribution of noradrenergic sympathetic nerves during local heating differs between leg and forearm at rest and with skin heating.

To reheat, or to not reheat: that is the question: the efficacy of a local reheating protocol on mechanisms of cutaneous vasodilatation.

The aim of this study is to determine the effect of repeated bouts of local skin heating on the roles of nitric oxide synthase (NOS) and sympathetic nerves in cutaneous vasodilatation. In 3 repeated-heating protocols skin blood flux of the forearm and leg was measured using laser-Doppler flowmetry and data are presented as cutaneous vascular conductance (CVC; flux/blood pressure). Local heating was performed from 33°C (thermoneutral) to 42°C at 0.5°C·10s(-1), allowed to cool passively for ~60-min, then reheated at the same rate. In protocol 1, CVC was measured in response to repeated heating. In protocol 2, NOS was inhibited with N(G)-nitro-l-arginine methyl ester (L-NAME) and in protocol 3, sympathetic nerve blockade was achieved with bretylium tosylate (BT), both infused via intradermal microdialysis. In protocol 1, there were no differences (P>0.05) in CVC at either the forearm (88±4 vs. 86±4%max) or the leg (97±4 vs. 96±6%max) between heating bouts. In protocol 2, no differences (P>0.05) in CVC were observed between heating bouts at L-NAME treated sites at either the forearm (55±3 vs. 51±4%max) or the leg (71±3 vs. 70±4%max) . In protocol 3, there were differences (P<0.001) between BT treated sites when comparing the first and second bouts of heating for both the forearm (75±3 vs. 88±4%max) and the leg (79±3 vs. 97±4%max). The effect of sympathetic blockade on CVC responses to local heating was abolished following repeated bouts of heating. Consequently, it is our suggestion that when examining mechanisms of skin blood flow control, investigators use single bouts of local heating.

Oscillatory cerebral blood flow is associated with impaired neurocognition and functional hyperemia in postural tachycardia syndrome during graded tilt.

We hypothesize that upright cognitive impairment in patients with postural tachycardia syndrome (POTS) is caused by reduced cerebral blood flow (CBF). The CBF velocity (CBF(v)) measured by transcranial Doppler ultrasound decreased excessively during 70° tilt in a minority of patients with intermittent hyperpnea/hypocapnia. Incremental tilt showed no difference in mean CBF(v). But N-back memory tasking indicated progressive compromised memory, reduced functional hyperemia, and reduced neurovascular coupling. Orthostasis caused slow oscillations in CBF(v) linked to oscillations in arterial pressure in patients with POTS. We also hypothesize that oscillatory CBF(v) degrades neurovascular coupling. We performed 2-back testing when subjects were in supine position and during incremental tilts to 15°, 30°, 45°, and 60° in 11 patients with POTS and 9 controls. Oscillatory arterial pressure, oscillatory CBF(v), and neurovascular coupling were similar in supine position. The oscillatory arterial pressure increased by 31%, 45%, 67%, and 93% in patients with POTS during tilt and remained unchanged in the controls. Oscillatory CBF(v) increased by 61%, 82%, 161%, and 264% in patients with POTS during tilt and remained unchanged in the controls. Functional hyperemia decreased from 4.1% to 3.0%, 1.1%, 0.2%, and to 0.04% in patients with POTS, but it was unchanged at 4% in the controls. Percent correct N-back responses decreased from 78% to 33% in patients with POTS, whereas they remained at 89% in the controls. In patients with POTS, oscillatory CBF(v) was linearly correlated with functional hyperemia (r(2)=0.76). Increased oscillatory CBF is associated with reduced neurovascular coupling and diminished cognitive performance in patients with POTS.

Altered oscillatory cerebral blood flow velocity and autoregulation in postural tachycardia syndrome.

Decreased upright cerebral blood flow (CBF) with hyperpnea and hypocapnia is seen in a minority of patients with postural tachycardia syndrome (POTS). More often, CBF is not decreased despite upright neurocognitive dysfunction. This may result from time-dependent changes in CBF. We hypothesized that increased oscillations in CBF occurs in POTS (N = 12) compared to healthy controls (N = 9), and tested by measuring CBF velocity (CBFv) by transcranial Doppler ultrasound of the middle cerebral artery, mean arterial pressure (MAP) and related parameters, supine and during 70° upright tilt. Autospectra for mean CBFv and MAP, and transfer function analysis were obtained over the frequency range of 0.0078-0.4 Hz. Upright HR was increased in POTS (125 ± 8 vs. 86 ± 2 bpm), as was diastolic BP (74 ± 3 vs. 65 ± 3 mmHg) compared to control, while peripheral resistance, cardiac output, and mean CBFv increased similarly with tilt. Upright BP variability (BPV), low frequency (LF) power (0.04-0.13 Hz), and peak frequency of BPV were increased in POTS (24.3 ± 4.1, and 18.4 ± 4.1 mmHg(2)/Hz at 0.091 Hz vs. 11.8 ± 3.3, and 8.8 ± 2 mmHg(2)/Hz c at 0.071 Hz), as was upright overall CBFv variability, low frequency power and peak frequency of CBFv variability (29.3 ± 4.7, and 22.1 ± 2.7 [cm/s](2)/Hz at.092 Hz vs. 14.7 ± 2.6, and 6.7 ± 1.2 [cm/s](2)/Hz at 0.077Hz). Autospectra were sharply peaked in POTS. LF phase was decreased in POTS (-14 ± 4 vs. -25 ± 10 degrees) while upright. LF gain was increased (1.51 ± 0.09 vs. 0.86 ± 0.12 [cm/s]/ mmHg) while coherence was increased (0.96 ± 0.01 vs. 0.80 ± 0.04). Increased oscillatory BP in upright POTS patients is closely coupled to oscillatory CBFv over a narrow bandwidth corresponding to the Mayer wave frequency. Therefore combined increased oscillatory BP and increased LF gain markedly increases CBFv oscillations in a narrow bandwidth. This close coupling of CBF to MAP indicates impaired cerebral autoregulation that may underlie upright neurocognitive dysfunction in POTS.

Blunted cerebral blood flow velocity in response to a nitric oxide donor in postural tachycardia syndrome.

Cognitive deficits are characteristic of postural tachycardia syndrome (POTS). Intact nitrergic nitric oxide (NO) is important to cerebral blood flow (CBF) regulation, neurovascular coupling, and cognitive efficacy. POTS patients often experience defective NO-mediated vasodilation caused by oxidative stress. We have previously shown dilation of the middle cerebral artery in response to a bolus administration of the NO donor sodium nitroprusside (SNP) in healthy volunteers. In the present study, we hypothesized a blunted middle cerebral artery response to SNP in POTS. We used combined transcranial Doppler-ultrasound to measure CBF velocity and near-infrared spectroscopy to measure cerebral hemoglobin oxygenation while subjects were in the supine position. The responses of 17 POTS patients were compared with 12 healthy control subjects (age: 14-28 yr). CBF velocity in POTS patients and control subjects were not different at baseline (75 ± 3 vs. 71 ± 2 cm/s, P = 0.31) and decreased to a lesser degree with SNP in POTS patients (to 71 ± 3 vs. 62 ± 2 cm/s, P = 0.02). Changes in total and oxygenated hemoglobin (8.83 ± 0.45 and 8.13 ± 0.48 µmol/kg tissue) were markedly reduced in POTS patients compared with control subjects (14.2 ± 1.4 and 13.6 ± 1.6 µmol/kg tissue), primarily due to increased venous efflux. The data indicate reduced cerebral oxygenation, blunting of cerebral arterial vasodilation, and heightened cerebral venodilation. We conclude, based on the present study outcomes, that decreased bioavailability of NO is apparent in the vascular beds, resulting in a downregulation of NO receptor sites, ultimately leading to blunted responses to exogenous NO.

Reduced cerebral blood flow with orthostasis precedes hypocapnic hyperpnea, sympathetic activation, and postural tachycardia syndrome.

Hyperventilation and reduced cerebral blood flow velocity can occur in postural tachycardia syndrome (POTS). We studied orthostatically intolerant patients, with suspected POTS, with a chief complaint of upright dyspnea. On the basis of our observations of an immediate reduction of cerebral blood flow velocity with orthostasis, we hypothesize that the resulting ischemic hypoxia of the carotid body causes chemoreflex activation, hypocapnic hyperpnea, sympathetic activation, and increased heart rate and blood pressure in this subset of POTS. We compared 11 dyspneic POTS subjects with 10 healthy controls during a 70° head-up tilt. In POTS subjects during initial orthostasis before blood pressure recovery; central blood volume and mean arterial pressure were reduced (P<0.025), resulting in a significant (P<0.001) decrease in cerebral blood flow velocity, which temporally preceded (17±6 s; P<0.025) a progressive increase in minute ventilation and decrease in end tidal CO2 (P<0.05) when compared with controls. Sympathoexcitation, measured by muscle sympathetic nerve activity, was increased in POTS (P<0.01) and inversely proportional to end tidal CO2 and resulted in an increase in heart rate (P<0.001), total peripheral resistance (P<0.025), and a decrease in cardiac output (P<0.025). The decrease in cerebral blood flow velocity and mean arterial pressure during initial orthostasis was greater (P<0.025) in POTS. Our data suggest that exaggerated initial central hypovolemia during initial orthostatic hypotension in POTS results in reduced cerebral blood flow velocity and postural hypocapnic hyperpnea that perpetuates cerebral ischemia. We hypothesize that sustained hypocapnia and cerebral ischemia produce sympathoexcitation, tachycardia, and a statistically significant increase in blood pressure.

Noninvasive examination of endothelial, sympathetic, and myogenic contributions to regional differences in the human cutaneous microcirculation.

The aim of this study was to examine whether there are regional differences in the cutaneous microvascular responses of the forearm and the leg. Utilizing a non-invasive measure (spectral analysis),we looked at the influence of the endothelial, sympathetic, and myogenic function between regions at thermoneutral conditions (33 °C) and in response to local skin warming (42 °C) using laser-Doppler flowmetry (LDF). We recruited 18 young, healthy participants, who visited the lab on 2 separate occasions. Participants were instrumented with LDF probes and local skin heater probe-holders, placed on the forearm or the leg. Blood pressure was recorded by oscillometry. At both 33 °C and during local skin warming to 42 °C, skin vasomotion for the forearm and leg were evaluated using spectral analysis of the LDF recordings. There were significant differences among all frequencies of interest between the forearm and the leg. At 33 °C the leg presented with higher (P=0.003) activity for endothelial (0.009-0.021 Hz), sympathetic (P=0.002) (0.021-0.052 Hz), and myogenic (P=0.004) (0.052-0.145 Hz) activity when compared to the forearm. In contrast, following 35 min of local skin warming, the forearm had greater endothelial (P=0.019), sympathetic (P=0.006), and myogenic (P=0.005) vasomotion than the leg. These outcomes indicate regional differences in the cutaneous microcirculation. The current results are similar to our previous work using invasive methods and pharmacological agents, indicating that non-invasive analyses may be useful in the diagnoses and understanding of the mechanisms that control the microvascular function of pathological conditions.

The regional differences in the contribution of nitric oxide synthase to skin blood flow at forearm and lower leg sites in response to local skin warming.

We investigated the role of nitric oxide synthase (NOS) on regional cutaneous vascular function at rest (thermoneutral conditions) and during the vasodilator response to increased local skin temperature (Tloc). Dorsal forearm and lateral leg sites were instrumented with microdialysis fibers, local heaters, and laser-Doppler probes. All sites were heated from 33 °C to 42 °C. Each limb had 1 skin site treated with l-NAME to inhibit NOS, and 1 site infused with lactated Ringer's to serve as a control. Basal cutaneous vascular conductance (CVC) was measured at 33 °C, forearm sites averaged 14 ± 1%max and 17 ± 1%max at l-NAME and control sites, respectively (P = 0.26). CVC sites in the leg were different between l-NAME (17 ± 1%max) and control (27 ± 2%max) (P = 0.04). CVC between the forearm and the leg across control sites differed (P < 0.05). In contrast, at l-NAME treated sites, there was no difference between the forearm and leg sites (P = 0.23). When Tloc was increased to 42 °C, CVC at the control sites differed between the forearm 93 ± 1%max and leg 98 ± 1%max (P = 0.02). There were no differences between the arm and leg at l-NAME treated sites at 42 °C (P = 0.45). The findings of the current study were that the contribution of nitric oxide (NO) to the vasodilator response to an elevated Tloc is consistent between the arm and the leg, and, under thermoneutral conditions (33 °C), NO plays a larger role in the basal vascular function in the legs than that of the forearm. Accordingly, these data suggest, in part, that the differences in basal CVC between the forearm and leg are due to NOS activity.

Effects of forearm vs. leg submersion in work tolerance time in a hot environment while wearing firefighter protective clothing.

This study compared physiological responses and total work tolerance time following forearm submersion (FS) or leg submersion (LS) in cool water, after performing work in a hot environment while wearing fire fighting protective clothing (FPC). Participants walked at 3.5 mph on a treadmill in a hot environment (WBGT 32.8 ± 0.9°C) until a rectal temperature (T(rec)) of 38.5°C was reached. Participants were then subjected to one of two peripheral cooling interventions, in a counterbalanced order. Forearms or lower legs were submerged in water (16.9 ± 0.8°C) for a total of 20 min, followed by a work tolerance trial. Results indicated no significant difference (p = 0.052) between work tolerance time (LS = 21.36 ± 5.35 min vs. FS = 16.27 ± 5.56 min). Similarly, there was no significant difference for T(rec) (p = 0.65), heart rate (HR) (p = 0.79), mean skin temperature (T(sk)) (p = 0.68), and rating of perceived exertion (RPE) (p = 0.54). However, LS ratings of thermal comfort (RTC) at Minute 14 (p = 0.03) were significantly lower for LS (10 ± 1) vs. FS (12 ± 1). Results indicate little difference between FS and LS for physiological measures. Despite a lack of statistical significance a 5-min (24%) increase was found during the work tolerance time following LS.