The vascular response to acute sauna heating is similar in young and middle-aged adults.

Sauna has been linked to a reduction of cardiovascular disease risk and is a promising nonpharmacological treatment for populations at risk of cardiovascular disease. This study examined the vascular response to an acute bout of sauna heating in young and middle-aged individuals. Ten young (25 ± 4 yr, 6 males and 4 females) and eight middle-aged adults (56 ± 4 yr, 4 males and 4 females) underwent 40 min of sauna exposure at 80°C. Esophageal and intramuscular temperatures, brachial and superficial femoral artery blood flow, artery diameter, and shear rates were recorded at baseline and following heat exposure. Brachial artery flow-mediated dilation (FMD) was measured at baseline and following 90 min of recovery. Esophageal and muscle temperatures increased similarly in the young and middle-aged adults by 1.5 ± 0.53 and 1.95 ± 0.70°C, respectively (P < 0.05). The shear rate increased by 170-200% (P < 0.001), while blood flow increased by 180-390% (P < 0.001) in the superficial femoral and brachial arteries, respectively, and did not differ between age groups (P = 0.190-0.899). Systolic blood pressure was reduced from 135 ± 17 to 122 ± 20 mmHg (P = 0.017) in middle-aged participants. These data indicate that young and middle-aged adults have similar vascular responses to acute sauna heating.NEW & NOTEWORTHY Sauna therapy has been shown to improve cardiovascular health and function in older adults and individuals with cardiovascular disease risk factors. Specifically, improvements in vascular function have been reported and have been attributed to the increased hemodynamic stimuli on the vasculature associated with thermal stress. The present study quantified this hemodynamic response to a sauna protocol associated with improved cardiovascular health across the lifespan. Our data show that middle-aged adults have the same shear rate and blood flow response to sauna as young adults.

Physiological assessment of a 16 day, 4385 km ultra-endurance mountain bike race: A case study.

The Tour Divide (TD) is a 4385 km ultra-endurance bicycle race that follows the continental divide from Canada to Mexico. In this case study, we performed a comprehensive molecular and physiological profile before and after the completion of the TD. Assessments were performed 35 days before the start (Pre-TD) and ∼36 h after the finish (Post-TD). Total energy expenditure was assessed during the first 9 days by doubly labelled water (2 H2 18 O), abdominal and leg tissue volumes via MRI, and graded exercise tests to quantify fitness and substrate preference. Vastus lateralis muscle biopsies were taken to measure mitochondrial function via respirometry, and vascular function was assessed using Doppler ultrasound. The 47-year-old male subject took 16 days 7 h 45 min to complete the route. He rode an average of 16.8 h/day. Neither maximal O2 uptake nor maximal power output changed pre- to post-TD. Measurement of total energy expenditure and dietary recall records suggested maintenance of energy balance, which was supported by the lack of change in body weight. The subject lost both appendicular and trunk fat mass and gained leg lean mass pre- to post-TD. Skeletal muscle mitochondrial and vascular endothelial function decreased pre- to post-TD. Overall, exercise performance was maintained despite reductions in muscle mitochondrial and vascular endothelial function post-TD, suggesting a metabolic reserve in our highly trained athlete.

Rapid onset vasodilation during baroreceptor loading and unloading.

The purpose of these experiments was to determine if the increase in vascular conductance following a single muscle contraction (50% of maximal voluntary contraction) (6 male and 6 female subjects) was altered during baroceptor loading and unloading. Rapid onset vasodilation (ROV) was determined by measuring brachial artery blood flow (Doppler ultrasound) and blood pressure (Finapress monitor). Brachial artery vascular conductance was calculated by dividing blood flow by mean arterial pressure. ROV was described by the area under the Δvascular conductance (VC)-time curve during the 30 s following muscle contraction. ROV was determined using chamber pressures of +20, +10, 0, -10, -20, and -40 mmHg (lower body positive and negative pressure, LBPP, and LBNP). We tested the hypothesis that the impact of baroreceptor loading and unloading produces a proportion change in ROV. The level of ROV following each contraction was proportional to the peak force (r2 = 0.393, P = 0.0001). Peak force was therefore used as a covariate in further analysis. ROV during application of -40 mmHg LBNP (0.345 ± 0.229 mL·mmHg-1) was lower than that observed at Control (0.532 ± 0.284 mL·mmHg-1, P = 0.034) and +20 mmHg LBPP (0.658 ± 0.364 mL·mmHg-1, P = 0.0008). ROV was linearly related to chamber pressure from -40 to +20 mmHg chamber pressure (r2 = 0.512, P = 0.022, n = 69) and from -20 to +10 mmHg chamber pressure (r2= 0.973, P < 0.0425, n = 45), Overall, vasoconstrictor tone altered with physiologically relevant baroreceptor loading and unloading resulted in a proportion change in ROV.NEW & NOTEWORTHY Rapid onset vasodilation (ROV) was linearly related to the peak force of each single 1-s muscle contraction. In addition, ROV is reduced by baroreceptor unloading (LBNP: -10, -120, and -40 mmHg) and increased by baroreceptor loading (LBPP: +10 and +20 mmHg). Without accounting for peak force and the level of baroreceptor engagement makes comparison of ROV in subjects of differing muscle size or strength untenable.

The influence of exercise volume and posture on exercise-induced plasma volume expansion.

Acute high-intensity interval exercise is known to expand plasma volume 24 h after exercise. Upright exercise posture plays a role in expanding plasma volume by influencing lymphatic outflow and redistributing albumin while supine exercise does not. We examined if further upright and weight-bearing exercises could further promote plasma volume expansion. We also tested the volume of intervals needed to induce plasma volume expansion. To test the first hypothesis, 10 subjects performed intermittent high-intensity exercise (4 min at 85% V̇O2max , 5 min at 40% V̇O2max repeated 8 times) on separate days on the treadmill and cycle ergometer. For the second study, 10 subjects performed four, six, and eight intervals of the same interval protocol on separate days. Changes in plasma volume were calculated from changes in hematocrit and hemoglobin. Transthoracic impedance (Z0 ) and plasma albumin were assessed while seated before and postexercise. Plasma volume increased 7.3% ± 4.4% and 6.3% ± 3.5% following treadmill and cycle ergometer exercise, respectively. For four, six, and eight intervals, plasma volume increased by 6.6% ± 4.0%, 4.7% ± 2.6%, and 4.2% ± 5.6%, respectively. The increases in plasma volume were similar for both exercise modes and all three exercise volumes. There were no differences in Z0 or plasma albumin content between trials. In conclusion, rapid plasma volume expansion following eight bouts of high-intensity intervals appears to be independent of upright exercise posture (treadmill versus cycle ergometer). Meanwhile, plasma volume expansion was similar after four, six, and eight intervals of cycle ergometry.

Cold-induced vasodilation in abstinent smokers with and without a 12-hour nicotine patch.

This study was designed to identify the effects of a 12-h nicotine patch administration on cold induced vasodilation (CIVD) in healthy young chronic smokers following 16 h of abstinence from smoking. Two laser Doppler probes and temperature thermocouples were placed on the dorsal part of the distal phalanx of the middle and ring fingers of 7 smokers (>12 cigarettes/day). Following 16 h of abstinence from smoking, smokers were tested with and without administration of a 21 mg transdermal nicotine patch (NicoDerm® ). Each participant's right hand was immersed in cold (~5°C) water for 40 min. Cutaneous vascular conductance (CVC) was calculated from non-invasive arterial finger blood pressure and skin blood flow and expressed as a percentage of peak CVC observed during hand skin heating to 44°C. For comparison purposes, the CIVD response of a non-smoking cohort without nicotine patch (n = 10) was also examined. Baseline CVC was similar in smokers and non-smokers (27.8 ± 12.6 CVC % peak). The initial vasoconstriction during cold-water immersion decreased skin blood flow to 4.0 ± 3.9 CVC % peak in both smokers and non-smokers. The onset of CIVD in smokers (4.5 ± 1.5 min) was delayed compared to non-smoker (3.3 ± 0.8 min, p < .05). The area under the CVC %peak-time curve during cold-water immersion averaged 1250 ± 388 CVC %peak · min in non-smokers which was larger (p < .05) than smokers with or without nicotine (789 ± 542 and 862 ± 517 CVC %peak · min, respectively). Chronic smoking impaired the CIVD response to cold-water immersion of the hand; however, the impaired CIVD response in 16 h of abstinence from smoking was not influenced by application of a 21 mg transdermal nicotine patch.

Role of nitric oxide synthase in human sweat gland output.

The mechanism by which nitric oxide synthase (NOS) inhibition impacts human sweating is unknown. We tested the hypothesis that the activation of NOS and release on nitric oxide acts to open K+ channels and enhance sweat gland output. Local sweat rate (LSR) was measured with a small sweat capsule mounted on the skin while sweating was initiated by intradermal electrical stimulation. Sigmoid shape stimulus-response curves were generated by plotting the area under the LSR-time curve (LSR AUC) versus log10 stimulus frequency and normalized to the peak AUC response during control trials. NOS inhibition alone reduced the peak sweat rate response to 81.5 ± 4.5% peak LSR AUC of that seen with lactated Ringer's (P = 0.0004). Fifty mM of tetraethylammonium chloride (TEA) alone reduced peak LSR (0.317 ± 0.060 vs. 0.511 ± 0.104 mg·min-1·cm-2, P = 0.03) and the peak LSR AUC response from 0.193 ± 0.170 to 0.158 ± 0.127 mg·cm-2 (P = 0.004). Delivery of a 20 mM nitro-l-arginine methyl ester (l-NAME) following 50 mM TEA produced a further decrease in the peak LSR AUC response to 0.095 ± 0.064 mg·cm-2 (≈20% reduction, P = 0.0145). These data support the hypothesis that sudomotor control of sweat gland activity is locally modulated by a functioning NOS system that appears to be additive and independent to the effect of blockade of K+ channels with TEA.NEW & NOTEWORTHY The contribution of nitric oxide synthase (NOS) to the process of cholinergic-mediated human eccrine sweat production is unclear. Using a novel model for cholinergic-mediated sweating in humans, I demonstrate that blocking the NOS system led to a reduction in local sweat rate (LSR). This reduction in LSR was maintained in the presence of K+ channel blockade with tetraethylammonium.

TEA-sensitive K+ channels and human eccrine sweat gland output.

Cholinergic-activated sweating depends on an influx of Ca2+ from extracellular fluid. It is thought that the opening of K+ channels on secretory epithelial cells facilitates Ca2+ entry. We examined the hypothesis that tetraethylammonium (TEA)-sensitive K+ channels participate in sweat production. We used a pre-post experimental design and initiated cholinergic-mediated sweating with intradermal electrical stimulation, monitored local sweat rate (SR) with a small sweat capsule mounted on the skin, and delivered 50 mM TEA via intradermal microdialysis. Local SR was activated by intradermal stimulation frequencies of 0.2-64 Hz, and we generated a sigmoid-shaped stimulus-response curve by plotting the area under the SR-time curve versus log10 stimulus frequency. Peak local SR was reduced from 0.372 ± 0.331 to 0.226 ± 0.190 mg·min-1·cm-2 (P = 0.0001) during application of 50 mM TEA, whereas the EC50 and Hill slopes were not altered. The global sigmoid-shaped stimulus-response curves for control and 50 mM TEA were significantly different (P < 0.0001), and the plateau region was significantly reduced (P = 0.0023) with the TEA treatment. The effect of TEA on peak local SR was similar in male and female subjects. However, we did note a small effect of sex on the shape of the stimulus-response curves during intradermal electrical stimulation. Overall, these data support the hypothesis that cholinergic control of sweat gland activity is modulated by the presence of TEA-sensitive K+ channels in human sweat gland epithelial cells.NEW & NOTEWORTHY The contribution of various potassium channels to the process of cholinergic-mediated human eccrine sweat production is unclear. Using a novel model for cholinergic-mediated sweating in humans, we provide evidence that tetraethylammonium-sensitive K+ channels (KCa1.1 and Kv channels) contribute to eccrine sweat production.

The Effect of Being Aerobically Active vs. Inactive on Cutaneous Vascular Conductance during Local Heat Stress in an Older Population.

Objective: To test the hypothesis that long- term aerobically trained elderly individuals have a greater amount of bioavailable nitric oxide (NO) and have a larger cutaneous vasodilation during local heat stress compared to their inactive elderly counterparts. Methods: Eight aerobically trained and 8 inactive older men (>60 years old) participated in this study. NO bioavailability in blood and intradermal dialysate were measured with an ozone based chemiluminescence NO analyzer. Cutaneous vasodilator response to local heating was obtained using laser Doppler velocimetry. Results: Whole blood NO were similar in older- trained and inactive subjects (0.75 ± 0.56 and 0.38 ± 0.32 µM, respectively; Mann-Whitney, p = 0.153), as was intradermal dialysate NO before (7.82 ± 6.32 and 4.18 ± 1.89 µM, respectively) and after local heating (7.16 ± 6.27 and 5.88 ± 3.97 µM, respectively, p = 0.354). The cutaneous vasodilator response of the older- inactive group was smaller than the older- trained group [Group-Time interaction, F(24, 264) = 12.0, p < 0.0001]. When compared to a young group the peak vasodilator response of the older- trained subjects was similar. However, the time to initial dilation was 3.1 and 2.2 times longer (p < 0.05) in older- inactive and older- trained subjects, respectively, compared to young subjects. Conclusions: Our data support the hypothesis that the age-related reductions in cutaneous vasodilation can possibly be restored by maintaining an aerobic training regimen (at least 3 years). However, some residual effects of aging remain, specifically a delayed cutaneous vasodilator response to local heating is still present in active older adults. We found no evidence for an increase in systemic or local NO-bioavailability with an extended commitment to aerobic fitness.

A model for in vivo analysis of sudomotor sympathetic C-fiber activation and human sweat gland output.

Quantitative assessment of small-fiber peripheral neuropathy often involves an evaluation of the interaction between the C-fiber sudomotor nerve and local sweat rate (SR). Typically, some sort of quantitative sudomotor axon reflex test (QSART) is performed to aid in diagnosing small-fiber dysfunction. The currently used QSART demonstrates only moderate test-retest reliability and therefore limits its usefulness in tracking small-fiber dysfunction. A new experimental model to examine small C-fiber function in the skin using intradermal electrical stimulation and simultaneous monitoring of SR is proposed. Using intradermal electrical stimulation (1.5 and 2.5 mA) and varying stimulus frequency from 0.2 to 64 Hz, a quantitative relationship between the area under the SR-time curve and log10 stimulus frequency is modeled using a four-parameter logistic equation, providing the following parameters: baseline, plateau, EC50, and Hill slope. The model has good to excellent repeatability within the same day (ICC = 0.98), on different days at the same skin site (ICC = 0.80), and when comparing two different skin sites (ICC = 0.78) with a small bias estimate and the line of identity always lying within the 95% limits of agreement. Atropine sulfate (0.1 mg/ml) blocked 90 ± 5% of the electrically induced sweating. Overall, the model provides control over sudomotor nerve activity and a quantitative assessment of SR. Finally, the ability to reproduce the quantitative stimulus-response curve on different days allows for a robust assessment of the relationship between the activation of a sympathetic C-fiber and local SR.NEW & NOTEWORTHY A model for quantitative assessment of C-fiber function in human skin using intradermal electrical stimulation and local sweat rate measurements has been developed. This new electrically induced sweating model is nonpainful and allows for a complete stimulus-response curve plotting the area under the local sweat rate-time curve vs. the log10 stimulus frequency. The model has good reproducibility and should provide a means of assessing the progression of small C-fiber peripheral neuropathy in humans.

Cutaneous Vasodilation during Local Heating: Role of Local Cutaneous Thermosensation.

We tested the hypothesis that cutaneous vasodilation during local skin heating in humans could be manipulated based upon the ability to desensitize TRPV4 ion channels by applying the thermal stimuli in a series of pulses. Each subject was instrumented with intradermal microdialysis probes in the dorsal forearm skin and perfused with 0.9% saline at 1.5 µl/min with local skin temperature controlled with a Peltier unit (9 cm2) at 34°C. Local skin temperature was manipulated for 50 min in two classic ways: a step increase to 38°C (0.1°C/s, n = 10), and a step increase to 42°C (n = 10). To desensitize TRPV4 ion channels local skin temperature was manipulated in the following way: pulsed increase to 38°C (1 pulse per min, 30 s duration, 1.0°C/s, n = 10), and 4) pulsed increase to 42°C (1.0°C/s, n = 9). Skin blood flow (SkBF, laser Doppler) was recorded directly over the middle microdialysis probe and the dialysate from all three probes were collected during baseline (34°C) and each skin heating period. The overall cutaneous vascular conductance (CVC) response to local heating was estimated from the area under the % CVCmax-time curve. The appearance of the neuropeptide calcitonin gene related peptide (CGRP) in dialysate did not change with skin heating in any protocol. For the skin temperature challenge of 34 to 38°C, the area under the % CVCmax-time curve averaged 1196 ± 295 (SD) % CVCmax•min, which was larger than the 656 ± 282% CVCmax•min during pulsed heating (p < 0.05). For the skin temperature challenge of 34 to 42°C, the area under the % CVCmax-time curve averaged 2678 ± 458% CVCmax•min, which was larger than the 1954 ± 533% CVCmax•min during pulsed heating (p < 0.05). The area under the % CVCmax•min curve, was directly proportional to the accumulated local skin thermal stress (in °C•min) (r2 = 0.62, p < 0.05, n = 39). This association indicates a critical role of local integration of thermosensitive receptors in mediating the cutaneous vasodilator response to local skin heating. Given that we saw no differences in the levels of CGRP in dialysate, the role of the vasoactive peptide CGRP in the cutaneous vasodilator response to local skin heating is not supported by our data.

Clinical symptoms, signs and tests for identification of impending and current water-loss dehydration in older people.

BACKGROUND: There is evidence that water-loss dehydration is common in older people and associated with many causes of morbidity and mortality. However, it is unclear what clinical symptoms, signs and tests may be used to identify early dehydration in older people, so that support can be mobilised to improve hydration before health and well-being are compromised. OBJECTIVES: To determine the diagnostic accuracy of state (one time), minimally invasive clinical symptoms, signs and tests to be used as screening tests for detecting water-loss dehydration in older people by systematically reviewing studies that have measured a reference standard and at least one index test in people aged 65 years and over. Water-loss dehydration was defined primarily as including everyone with either impending or current water-loss dehydration (including all those with serum osmolality ≥ 295 mOsm/kg as being dehydrated). SEARCH METHODS: Structured search strategies were developed for MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL, LILACS, DARE and HTA databases (The Cochrane Library), and the International Clinical Trials Registry Platform (ICTRP). Reference lists of included studies and identified relevant reviews were checked. Authors of included studies were contacted for details of further studies. SELECTION CRITERIA: Titles and abstracts were scanned and all potentially relevant studies obtained in full text. Inclusion of full text studies was assessed independently in duplicate, and disagreements resolved by a third author. We wrote to authors of all studies that appeared to have collected data on at least one reference standard and at least one index test, and in at least 10 people aged ≥ 65 years, even where no comparative analysis has been published, requesting original dataset so we could create 2 x 2 tables. DATA COLLECTION AND ANALYSIS: Diagnostic accuracy of each test was assessed against the best available reference standard for water-loss dehydration (serum or plasma osmolality cut-off ≥ 295 mOsm/kg, serum osmolarity or weight change) within each study. For each index test study data were presented in forest plots of sensitivity and specificity. The primary target condition was water-loss dehydration (including either impending or current water-loss dehydration). Secondary target conditions were intended as current (> 300 mOsm/kg) and impending (295 to 300 mOsm/kg) water-loss dehydration, but restricted to current dehydration in the final review.We conducted bivariate random-effects meta-analyses (Stata/IC, StataCorp) for index tests where there were at least four studies and study datasets could be pooled to construct sensitivity and specificity summary estimates. We assigned the same approach for index tests with continuous outcome data for each of three pre-specified cut-off points investigated.Pre-set minimum sensitivity of a useful test was 60%, minimum specificity 75%. As pre-specifying three cut-offs for each continuous test may have led to missing a cut-off with useful sensitivity and specificity, we conducted post-hoc exploratory analyses to create receiver operating characteristic (ROC) curves where there appeared some possibility of a useful cut-off missed by the original three. These analyses enabled assessment of which tests may be worth assessing in further research. A further exploratory analysis assessed the value of combining the best two index tests where each had some individual predictive ability. MAIN RESULTS: There were few published studies of the diagnostic accuracy of state (one time), minimally invasive clinical symptoms, signs or tests to be used as screening tests for detecting water-loss dehydration in older people. Therefore, to complete this review we sought, analysed and included raw datasets that included a reference standard and an index test in people aged ≥ 65 years.We included three studies with published diagnostic accuracy data and a further 21 studies provided datasets that we analysed. We assessed 67 tests (at three cut-offs for each continuous outcome) for diagnostic accuracy of water-loss dehydration (primary target condition) and of current dehydration (secondary target condition).Only three tests showed any ability to diagnose water-loss dehydration (including both impending and current water-loss dehydration) as stand-alone tests: expressing fatigue (sensitivity 0.71 (95% CI 0.29 to 0.96), specificity 0.75 (95% CI 0.63 to 0.85), in one study with 71 participants, but two additional studies had lower sensitivity); missing drinks between meals (sensitivity 1.00 (95% CI 0.59 to 1.00), specificity 0.77 (95% CI 0.64 to 0.86), in one study with 71 participants) and BIA resistance at 50 kHz (sensitivities 1.00 (95% CI 0.48 to 1.00) and 0.71 (95% CI 0.44 to 0.90) and specificities of 1.00 (95% CI 0.69 to 1.00) and 0.80 (95% CI 0.28 to 0.99) in 15 and 22 people respectively for two studies, but with sensitivities of 0.54 (95% CI 0.25 to 0.81) and 0.69 (95% CI 0.56 to 0.79) and specificities of 0.50 (95% CI 0.16 to 0.84) and 0.19 (95% CI 0.17 to 0.21) in 21 and 1947 people respectively in two other studies). In post-hoc ROC plots drinks intake, urine osmolality and axillial moisture also showed limited diagnostic accuracy. No test was consistently useful in more than one study.Combining two tests so that an individual both missed some drinks between meals and expressed fatigue was sensitive at 0.71 (95% CI 0.29 to 0.96) and specific at 0.92 (95% CI 0.83 to 0.97).There was sufficient evidence to suggest that several stand-alone tests often used to assess dehydration in older people (including fluid intake, urine specific gravity, urine colour, urine volume, heart rate, dry mouth, feeling thirsty and BIA assessment of intracellular water or extracellular water) are not useful, and should not be relied on individually as ways of assessing presence or absence of dehydration in older people.No tests were found consistently useful in diagnosing current water-loss dehydration. AUTHORS' CONCLUSIONS: There is limited evidence of the diagnostic utility of any individual clinical symptom, sign or test or combination of tests to indicate water-loss dehydration in older people. Individual tests should not be used in this population to indicate dehydration; they miss a high proportion of people with dehydration, and wrongly label those who are adequately hydrated.Promising tests identified by this review need to be further assessed, as do new methods in development. Combining several tests may improve diagnostic accuracy.

The time course of dexamethasone delivery using iontophoresis through human skin, measured via microdialysis.

STUDY DESIGN: Controlled laboratory study. OBJECTIVE: To determine the time course of dexamethasone sodium phosphate (Dex-P) during iontophoresis to underlying tissues using microdialysis. BACKGROUND: In human participants, real-time information of Dex-P transdermal delivery during iontophoresis is unknown. METHODS: Sixty-four healthy male participants (mean ± SD age, 24.2 ± 3.3 years; height, 181.8 ± 26.1 cm; mass, 82.4 ± 11.8 kg; subcutaneous fat thickness, 0.61 ± 0.19 cm) were randomly assigned into 1 of 6 groups: (1) 1-mA current, 1-mm probe depth; (2) 1-mA current, 4-mm probe depth; (3) 2-mA current, 1-mm probe depth; (4) 2-mA current, 4-mm probe depth; (5) in vivo retrodialysis; and (6) skin perfusion flowmetry. Microdialysis probes were used to assess the combined recovery (Dex-total) of Dex-P, dexamethasone, and its metabolite. RESULTS: There was no difference in Dex-total between current intensities (P = .99), but a greater amount of Dex-total was recovered superficially at 1 mm compared to the 4-mm depth (P<.0001). Peak concentration mean ± SD values for the 1- and 2-mA currents at 1 mm were 10.8 ± 8.1 and 7.7 ± 5.5 µg/mL, and at 4 mm were 2.0 ± 0.8 and 1.3 ± 0.9 µg/mL, respectively. Peak skin perfusion was 741.4% ± 408.7% and 711.6% ± 260.8% at baseline for 1- and 2-mA intensities, respectively. Skin perfusion returned to baseline levels earlier during 1-mA intensity at a 110 mA · min dose within the treatment, compared to 2 mA at 60 minutes posttreatment. CONCLUSION: Transdermal delivery of Dex-P during iontophoresis was successfully measured in vivo through human skin. Measurable concentrations of Dex-total were found regardless of current intensity. Although current-induced vasodilation occurred, it did not significantly affect the tissue accumulation of Dex-total.

Effect of whole body vibration on skin blood flow and nitric oxide production.

BACKGROUND: Vascular dysfunction due to hyperglycemia in individuals with diabetes is a factor contributing to distal symmetric polyneuropathy (DSPN). Reactive oxygen species reduce the bioavailability of nitric oxide (NO), a powerful vasodilator, resulting in reduced circulation and nerve ischemia. Increases in blood NO concentrations and circulation have been attributed to whole body vibration (WBV). The purpose of this study was to the determine the effects of low-frequency, low-amplitude WBV on whole blood NO concentrations and skin blood flow (SBF) in individuals with symptoms of DSPN. METHODS: Ten patients with diabetes and impaired sensory perception in the lower limbs participated in this crossover study. Each submitted to 2 treatment conditions, WBV and sham, with a 1-week washout period between. Blood draws for NO analysis and laser Doppler imager scans of SBF were performed before, immediately after, and following a 5-minute recovery of each of the treatments. RESULTS: Low-frequency, low-amplitude WBV significantly increased SBF compared to the sham condition (F(2,18) = 5.82, P = .0115). Whole blood NO concentrations did not differ between the WBV and sham conditions immediately or 5 minutes after treatment (F(2,18) = 1.88, P = .1813). CONCLUSIONS: These findings demonstrate that patients with diabetes respond to WBV with increased SBF compared to the sham condition. The implication is that WBV is a potential nonpharmacological therapy for neurovascular complications of diabetes.

Changes in dermal interstitial ATP levels during local heating of human skin.

Heating skin is believed to activate vanilloid type III and IV transient receptor potential ion channels (TRPV3, TRPV4, respectively), resulting in the release of ATP into the interstitial fluid. We examined the hypothesis that local skin heating would result in an accumulation of ATP in the interstitial fluid that would be related with a rise in skin blood flow (SkBF) and temperature sensation. Two microdialysis probes were inserted into the dermis on the dorsal aspect of the forearm in 15 young, healthy subjects. The probed skin was maintained at 31°C, 35°C, 39°C and 43°C for 8 min periods, during which SkBF was monitored as cutaneous vascular conductance (CVC). Dialysate was collected and analysed for ATP ([ATP](d)) using a luciferase-based assay, and ratings of perceived warmth were taken at each temperature. At a skin temperature of 31°C, [ATP](d) averaged 18.93 ± 4.06 nm and CVC averaged 12.57 ± 1.59% peak. Heating skin to 35°C resulted in an increase in CVC (17.63 ± 1.27% peak; P < 0.05), but no change in [ATP](d). Heating skin to 39°C and 43°C resulted in a decreased [ATP](d) (5.88 ± 1.68 nm and 8.75 ± 3.44 nm, respectively; P < 0.05), which was accompanied by significant elevations in CVC (38.90 ± 1.37% peak and 60.32 ± 1.95% peak, respectively; P < 0.05). Ratings of perceived warmth increased in proportion to the increase in skin temperature (r(2) = 0.75, P < 0.05). In conclusion, our data indicate that an accumulation of interstitial ATP does not occur during local heating, and therefore does not have a role in temperature sensation or the dilator response in human skin. Nevertheless, the low threshold of dilatation (35°C) indicates a possible role for the TRPV3, TRPV4 channels or the sensitization of other ion channels in mediating the dilator response.

Metabolic energy expenditure during spring-loaded crutch ambulation.

CONTEXT: Individuals using traditional axillary crutches to ambulate expend approximately twice as much energy as individuals who perform able-bodied gait. A relatively novel spring-loaded crutch now being marketed may reduce metabolic energy expenditure during crutch ambulation. This idea, however, had not yet been tested. OBJECTIVE: To determine whether the novel spring-loaded crutch reduces oxygen consumption during crutch ambulation, relative to traditional-crutch ambulation. A secondary purpose was to evaluate the design for subject-perceived comfort and ease of use. DESIGN: Within-subject. SETTING: Indoor track. PARTICIPANTS: 10 able-bodied men and 10 able-bodied women. INTERVENTIONS: The independent variable was crutch design. Each subject ambulated using 3 different crutch designs (traditional, spring-loaded, and modified spring-loaded), in a randomized order. MAIN OUTCOME MEASURES: The primary dependent variable was oxygen consumption. Secondary dependent variables were subject-perceived comfort and ease of use, as rated by the subjects using a 100-mm visual analog scale. Dependent variables were compared among the 3 crutch designs using a 1-way repeated-measures ANOVA (α = .05). RESULTS: Oxygen consumption during spring-loaded-crutch ambulation (17.88 ± 2.13 mL · kg⁻¹ · min⁻¹) was 6.2% greater (P = .015; effect size [ES] = .50) than during traditional axillary-crutch ambulation (16.84 ± 2.08 mL · kg⁻¹ · min⁻¹). There was no statistically significant difference (P = .068; ES = -.45) for oxygen consumption between spring-loaded-crutch ambulation and ambulation using the modified crutch (17.03 ± 1.61 mL · kg⁻¹ · min⁻¹). Subjects perceived the spring-loaded crutch to be more comfortable (P < .001; ES = .56) than the traditional crutch. There was no difference (P = .159; ES = -.09) between the spring-loaded and traditional crutches for subject-perceived ease of use. CONCLUSIONS: Compared with traditional axillary crutches, the novel spring-loaded crutch may be more comfortable but does not appear to benefit subjects via reduced metabolic energy expenditure.

Gastric emptying after pickle-juice ingestion in rested, euhydrated humans.

CONTEXT: Small volumes of pickle juice (PJ) relieve muscle cramps within 85 seconds of ingestion without significantly affecting plasma variables. This effect may be neurologic rather than metabolic. Understanding PJ's gastric emptying would help to strengthen this theory. OBJECTIVE: To compare gastric emptying and plasma variables after PJ and deionized water (DIW) ingestion. DESIGN: Crossover study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Ten men (age  =  25.4 ± 0.7 years, height  =  177.1 ± 1.6 cm, mass  =  78.1 ± 3.6 kg). INTERVENTION(S): Rested, euhydrated, and eunatremic participants ingested 7 mL·kg⁻¹ body mass of PJ or DIW on separate days. MAIN OUTCOME MEASURE(S): Gastric volume was measured at 0, 5, 10, 20, and 30 minutes postingestion (using the phenol red dilution technique). Percentage changes in plasma volume and plasma sodium concentration were measured preingestion (-45 minutes) and at 5, 10, 20, and 30 minutes postingestion. RESULTS: Initial gastric volume was 624.5 ± 27.4 mL for PJ and 659.5 ± 43.8 mL for DIW (P > .05). Both fluids began to empty within the first 5 minutes (volume emptied: PJ  =  219.2 ± 39.1 mL, DIW  =  305.0 ± 40.5 mL, P < .05). Participants who ingested PJ did not empty further after the first 5 minutes (P > .05), whereas in those who ingested DIW, gastric volume decreased to 111.6 ± 39.9 mL by 30 minutes (P < .05). The DIW group emptied faster than the PJ group between 20 and 30 minutes postingestion (P < .05). Within 5 minutes of PJ ingestion, plasma volume decreased 4.8% ± 1.6%, whereas plasma sodium concentration increased 1.6 ± 0.5 mmol·L⁻¹ (P < .05). Similar changes occurred after DIW ingestion. Calculated plasma sodium content was unchanged for both fluids (P > .05). CONCLUSIONS: The initial decrease in gastric volume with both fluids is likely attributable to gastric distension. Failure of the PJ group to empty afterward is likely due to PJ's osmolality and acidity. Cardiovascular reflexes resulting from gastric distension are likely responsible for the plasma volume shift and rise in plasma sodium concentration despite nonsignificant changes in plasma sodium content. These data support our theory that PJ does not relieve cramps via a metabolic mechanism.

Three percent hypohydration does not affect threshold frequency of electrically induced cramps.

PURPOSE: Dehydration is hypothesized to cause exercise-associated muscle cramps. The theory states that dehydration contracts the interstitial space, thereby increasing the pressure on nerve terminals and cramps ensue. Research supporting this theory is often observational, and fatigue is rarely controlled. Inducing cramps with electrical stimulation minimizes many of the confounding factors associated with exercise-induced cramps (e.g., fatigue, metabolites). Thus, our goal was to minimize fatigue and determine whether hypohydration decreases the electrical stimuli required to elicit cramping (termed "threshold frequency"). METHODS: Ten males cycled for 30-min bouts with their nondominant leg at 41°C and 15% relative humidity until they lost ~3% of their body mass (~2 h). Dominant leg flexor hallucis brevis muscle cramps were induced before and after hypohydration, and threshold frequency was recorded. Plasma osmolality (OSMp) characterized hydration status. Total sweat electrolytes (Na+, K+, Mg2+, and Ca2+) lost during exercise was calculated. Subjects repeated the protocol 1 wk later. RESULTS: Subjects were hypohydrated after exercise (preexercise OSMp = 282.5 T 1 mOsm·kg−¹ H2O, postexercise OSMp = 295.1 ± 1 mOsm·kg−¹ H2O, P < 0.001). Subjects lost 3.0% ± 0.1% of their body mass, 144.9 ± 9.8 mmol of Na+, 11.2 ± 0.4 mmol of K+, 3.3 ± 0.3 mmol of Mg2+, and 3.1 ± 0.1 mmol of Ca2+. Mild hypohydration with minimal neuromuscular fatigue did not affect threshold frequency (euhydrated = 23.7 ± 1.5 Hz, hypohydrated = 21.3 ± 1.4 Hz; F1,9 = 2.81, P = 0.12). CONCLUSIONS: Mild hypohydration with minimal neuromuscular fatigue does not seem to predispose individuals to cramping. Thus, cramps may be more associated with neuromuscular fatigue than dehydration/electrolyte losses. Health care professionals may have more success preventing exercise-associated muscle cramp by focusing on strategies that minimize neuromuscular fatigue rather than dehydration. However, the effect of greater fluid losses on cramp threshold frequency is unknown and merits further research.

Myogenic regulatory factor response to resistance exercise volume in skeletal muscle.

This study examined the impact of resistance exercise volume on myoD and myogenin in rodent quadriceps muscle. Six-month-old male Sprague-Dawley rats (316 +/- 2 g) performed either low-volume (LV; 10 sets x 10 contractions) or high-volume (HV; 20 sets x 10 contractions) resistance exercise at 75% one-repetition maximum. Muscles were analyzed for myogenin and myoD mRNA and protein expression 6, 12, 24 and 48 h post-exercise. In red quadriceps (RQ), myogenin mRNA was significantly elevated at 6 h following LV and this response was greater than HV at 6 h, while myogenin protein was significantly increased at 6 and 12 h following LV but only at 12 h following HV (P < 0.05). MyoD mRNA was increased at 6 and 12 h following LV and at 12 h following HV, while myoD protein was slightly decreased (LV; P < 0.05) or unchanged over time (HV). No changes were detected within the white quadriceps muscle. We conclude that acute resistance exercise can activate myogenin and myoD expression levels in RQ, but when exercise volume is doubled these myogenic responses are not proportional but delayed and blunted possibly because of excessive damage/injury. Further work is needed to determine the consequences of these specific myogenic responses on muscle hypertrophy following high-volume resistance exercise training.

Reflex inhibition of electrically induced muscle cramps in hypohydrated humans.

INTRODUCTION: Anecdotal evidence suggests that ingesting small volumes of pickle juice relieves muscle cramps within 35 s of ingestion. No experimental evidence exists supporting the ingestion of pickle juice as a treatment for skeletal muscle cramps. METHODS: On two different days (1 wk apart), muscle cramps were induced in the flexor hallucis brevis (FHB) of hypohydrated male subjects (approximately 3% body weight loss and plasma osmolality approximately 295 mOsm x kg(-1) H2O) via percutaneous tibial nerve stimulation. Thirty minutes later, a second FHB muscle cramp was induced and was followed immediately by the ingestion of 1 mL x kg(-1) body weight of deionized water or pickle juice (73.9 +/- 2.8 mL). RESULTS: Cramp duration and FHB EMG activity during the cramp were quantified, as well as the change in plasma constituents. Cramp duration (water = 151.9 +/- 12.9 s and pickle juice = 153.2 +/- 23.7 s) and FHB EMG activity (water = 60% +/- 6% and pickle juice = 68% +/- 9% of maximum voluntary isometric contraction EMG activity) were similar during the initial cramp induction without fluid ingestion (P > 0.05). During FHB muscle cramp induction combined with fluid ingestion, FHB EMG activity was again similar (water = 55% +/- 9% and pickle juice = 66% +/- 9% of maximum voluntary isometric contraction EMG activity, P > 0.05). However, cramp duration was 49.1 +/- 14.6 s shorter after pickle juice ingestion than water (84.6 +/- 18.5 vs 133.7 +/- 15.9 s, respectively, P < 0.05). The ingestion of water or pickle juice had little impact on plasma composition 5 min after ingestion. CONCLUSIONS: Pickle juice, and not deionized water, inhibits electrically induced muscle cramps in hypohydrated humans. This effect could not be explained by rapid restoration of body fluids or electrolytes. We suspect that the rapid inhibition of the electrically induced cramps reflects a neurally mediated reflex that originates in the oropharyngeal region and acts to inhibit the firing of alpha motor neurons of the cramping muscle.