Effect of histamine-receptor antagonism on the circulating inflammatory cell and cytokine response to exercise: A pilot study.

The purpose of this study was to gain insight into histamine's role in the exercise inflammatory response and recovery from exercise. To explore this, young healthy participants (n = 12) performed 300 eccentric leg extensions under control (Placebo) versus histamine H1 and H2 receptor antagonism (Blockade) in a randomized cross-over study. Circulating leukocytes and cytokines were measured for 72 h after exercise. Circulating leukocytes were elevated at 6 and 12 h after exercise (p < 0.05) with the peak response being a 44.1 ± 11.7% increase with Blockade versus 13.7 ± 6.6% with Placebo (both p < 0.05 vs. baseline, but also p < 0.05 between Blockade and Placebo). Of the cytokines that were measured, only MCP-1 was elevated following exercise. The response at 6 h post-exercise was a 104.0 ± 72.5% increase with Blockade versus 93.1 ± 41.9% with Placebo (both p < 0.05 vs. baseline, p = 0.82 between Blockade and Placebo). The main findings of the present investigation were that taking combined histamine H1 and H2 receptor antagonists augmented the magnitude but not the duration of the increase of circulating immune cells following exercise. This suggests histamine is not only exerting a local influence within the skeletal muscle but that it may influence the systemic inflammatory patterns.

Paradoxical breathing during sleep is associated with increased sleep apnea and reduced ventilatory capacities in high-level spinal cord injury.

Sleep-disordered breathing is highly prevalent in individuals with high-level spinal cord injury. In addition, chest mechanics are known to be altered, leading to paradoxical breathing. Here we investigated the interaction between paradoxical breathing and sleep quality in these patients, and its association with measurements of respiratory function, hypercapnic ventilatory response and peak exercise ventilation. Home-based polysomnography was performed in 13 patients with spinal cord injury (C4 to T4) untreated for sleep-disordered breathing. We defined paradoxical breathing as counterphase between thoracic and abdominal movements during slow-wave and rapid eye movement sleep. Sleep quality, pulmonary function, hypercapnic ventilatory responses and peak exercise ventilation were compared between those with and without paradoxical breathing. Half of individuals presented with nocturnal paradoxical breathing. Despite similar age, body mass index, injury level, time since injury, and respiratory function, those with paradoxical breathing had higher apnea-hypopnea index (13 ± 8 versus 5 ± 3 events per hr) and average sleep heart rate (67 ± 12 versus 54 ± 4 bpm; p < 0.05). Moreover, paradoxical breathing was associated with lower hypercapnic ventilatory response (slope: 0.35 ± 0.17 versus 0.96 ± 0.38) and lower peak exercise ventilation (33 ± 4 versus 48 ± 12 L min-1 ; p < 0.05). Nocturnal respiratory muscle desynchronization could play a role in the pathophysiology of sleep apnea, and could relate to low ventilatory responses to both hypercapnia and exercise in high-level spinal cord injury. Polysomnography may be an important diagnostic tool for these patients for whom therapeutic approaches should be considered to treat this abnormality.

Nitric oxide-mediated vasodilation in human bone.

OBJECTIVE: Regulation of blood flow to bone is critical but poorly understood, particularly in humans. This study aims to determine whether nitric oxide (NO), a major regulator of vascular tone to other tissues, contributes also to the regulation of blood flow to bone. METHODS: In young healthy adults (n = 16, 8F, 8M), we characterized NO-mediated vasodilation in the tibia in response to sublingual nitroglycerin and contrasted it to lower leg. Blood flow responses were assessed in supine individuals by continuously measuring tibial total hemoglobin (tHb) via near-infrared spectroscopy and lower leg blood flow (LBF) as popliteal flow velocity via Doppler ultrasound in the same leg. RESULTS: LBF increased by Δ9.73 ± 0.66 cm/s and peaked 4.4 min after NO administration and declined slowly but remained elevated (Δ3.63 ± 0.60 cm/s) at 10 min. In contrast, time to peak response was longer and smaller in magnitude in the tibia as tHb increased Δ2.08 ± 0.22 µM and peaked 5.3 min after NO administration and declined quickly but remained elevated (Δ0.87±0.22 µM) at 10 min (p = .01). CONCLUSIONS: In young adults, the tibial vasculature demonstrates robust NO-mediated vasodilation, but tHb is delayed and diminishes faster compared to LBF, predominately reflective of skeletal muscle responses. Thus, NO-mediated vasodilation in bone may be characteristically different from other vascular beds.

Exercise Training Does Not Attenuate Cardiac Atrophy or Loss of Function in Individuals With Acute Spinal Cord Injury: A Pilot Study.

OBJECTIVE: To investigate the effects of 2 modes of exercise training, upper-body alone, and the addition of electrical stimulation of the lower body, to attenuate cardiac atrophy and loss of function in individuals with acute spinal cord injury (SCI). DESIGN: Randomized controlled trial. SETTING: Rehabilitation Hospital. PARTICIPANTS: Volunteers (N=27; 5 women, 22 men) who were <24 months post SCI. INTERVENTIONS: Volunteers completed either 6 months of no structured exercise (Control), arm rowing (AO), or a combination of arm rowing with electrical stimulation of lower body paralyzed muscle (functional electrical stimulation [FES] rowing). MAIN OUTCOME MEASURES: Transthoracic echocardiography was performed on each subject prior to and 6 months after the intervention. The relations between time since injury and exercise type to cardiac structure and function were assessed via 2-way repeated-measures analysis of variance and with multilevel linear regression. RESULTS: Time since injury was significantly associated with a continuous decline in cardiac structure and systolic function, specifically, a reduction in left ventricular mass (0.197 g/month; P=.049), internal diameter during systole (0.255 mm/month; P<.001), and diastole (0.217 mm/month; P=.019), as well as cardiac output (0.048 L/month, P=.019), and left ventricular percent shortening (0.256 %/month; P=.027). These associations were not differentially affected by exercise (Control vs AO vs FES, P>.05). CONCLUSIONS: These results indicate that within the subacute phase of recovery from SCI there is a linear loss of left ventricular cardiac structure and systolic function that is not attenuated by current rehabilitative aerobic exercise practices. Reductions in cardiac structure and function may increase the risk of cardiovascular disease in individuals with SCI and warrants further interventions to prevent cardiac decline.

The effect of local passive heating on skeletal muscle histamine concentration: implications for exercise-induced histamine release.

Aerobic exercise induces mast cell degranulation and increases histamine formation by histidine decarboxylase, resulting in an ∼150% increase in intramuscular histamine. The purpose of this study was to determine if the increase in skeletal muscle temperature associated with exercise is sufficient to explain this histamine response. Specifically, we hypothesized that local passive heating that mimics the magnitude and time course of changes in skeletal muscle temperature observed during exercise would result in increased intramuscular histamine concentrations comparable to exercising values. Seven subjects participated in the main study in which pulsed short-wave diathermy was used to passively raise the temperature of the vastus lateralis over 60 min. Heating increased intramuscular temperature from 32.6°C [95% confidence interval (CI) 32.0°C to 33.2°C] to 38.9°C (38.7°C to 39.2°C) (P < 0.05) and increased intramuscular histamine concentration from 2.14 ng/mL (1.92 to 2.36 ng/mL) to 2.97 ng/mL (2.57 to 3.36 ng/mL) (P < 0.05), an increase of 41%. In a follow-up in vitro experiment using human-derived cultured mast cells, heating to comparable temperatures did not activate mast cell degranulation. Therefore, it appears that exercise-associated changes in skeletal muscle temperature are sufficient to generate elevations in intramuscular histamine concentration. However, this thermal effect is most likely due to changes in de novo histamine formation via histidine decarboxylase and not due to degranulation of mast cells. In conclusion, physiologically relevant increases in skeletal muscle temperature explain part, but not all, of the histamine response to aerobic exercise. This thermal effect may be important in generating positive adaptations to exercise training.NEW & NOTEWORTHY The "exercise signal" that triggers histamine release within active skeletal muscle during aerobic exercise is unknown. By mimicking the magnitude and time course of increasing skeletal muscle temperature observed during aerobic exercise, we demonstrate that part of the exercise-induced rise in histamine is explained by a thermal effect, with in vitro experiments suggesting this is most likely via de novo histamine formation. This thermal effect may be important in generating positive adaptations to exercise training.

Reductions in Cardiac Structure and Function 24 Months After Spinal Cord Injury: A Cross-Sectional Study.

OBJECTIVE: To determine the alterations in cardiac structure and function that occur in the months after spinal cord injury (SCI). STUDY DESIGN: Cross-sectional SETTING: Rehabilitation Hospital PARTICIPANTS: Volunteers (N=29; 4 women, 25 men) between 3 and 24 months after SCI. MAIN OUTCOME MEASURES: Transthoracic echocardiography was performed on each volunteer. The relationships between time since injury and neurologic and sensory levels of injury to cardiac structure and function were assessed via multiple linear regression. RESULTS: Time since injury was most strongly associated with reductions in left ventricular end diastolic volume (r2=0.156; P=.034), end systolic volume (r2=0.141; P=.045), and mass (r2=0.138; P=.047). These structural changes were paralleled by reduced stroke volume (r2=0.143; P=.043) and cardiac output (r2=0.317; P=<.001). The reductions in left ventricular structure and systolic function were not differentially affected by neurologic or sensory levels of injury (P=.084-.921). CONCLUSIONS: These results suggest progressive reductions in left ventricular structure and systolic function between 3 and 24 months after SCI that occur independent of neurologic and sensory levels of injury.

Effect of histamine-receptor antagonism on leg blood flow during exercise.

Histamine mediates vasodilation during inflammatory and immune responses, as well as following endurance exercise. During exercise, intramuscular histamine concentration increases, and its production, appears related to exercise intensity and duration. However, whether histamine contributes to exercise hyperemia and promotes exercise blood flow in an intensity- or duration-dependent pattern is unknown. The purpose of this study was to compare leg blood flow across a range of exercise intensities, before and after prolonged exercise, with and without histamine-receptor antagonism. It was hypothesized that combined oral histamine H1/H2-receptor antagonism would decrease leg blood flow, and the effect would be greater at higher intensities and following prolonged exercise. Sixteen (7F, 9M) volunteers performed single-leg knee-extension exercise after consuming either placebo or combined histamine H1/H2-receptor antagonists (Blockade). Exercise consisted of two graded protocols at 20, 40, 60, and 80% of peak power, separated by 60 min of knee-extension exercise at 60% of peak power. Femoral artery blood flow was measured by ultrasonography. Femoral artery blood flow increased with exercise intensity up to 2,660 ± 97 mL/min at 80% of peak power during Placebo (P < 0.05). Blood flow was further elevated with Blockade to 2,836 ± 124 mL/min (P < 0.05) at 80% peak power (9.1 ± 4.8% higher than placebo). These patterns were not affected by prolonged exercise (P = 0.13). On average, femoral blood flow during prolonged exercise was 12.7 ± 2.8% higher with Blockade vs. Placebo (P < 0.05). Contrary to the hypothesis, these results suggest that histamine receptor antagonism during exercise, regardless of intensity or duration, increases leg blood flow measured by ultrasonography.NEW & NOTEWORTHY Leg blood flow during exercise was increased by taking antihistamines, which block the receptors for histamine, a molecule often associated with inflammatory and immune responses. The elevated blood flow occurred over exercise intensities ranging from 20 to 80% of peak capacity and during exercise of 60 min duration. These results suggest that exercise-induced elevations in histamine concentrations are involved in novel, poorly understood, and perhaps complex ways in the exercise response.

Effect of Time of Day on Sustained Postexercise Vasodilation Following Small Muscle-Mass Exercise in Humans.

INTRODUCTION: Previous studies observed diurnal variation in hemodynamic responses during recovery from whole-body exercise, with vasodilation appearing greater after evening versus morning sessions. It is unclear what mechanism(s) underlie this response. Since small muscle-mass exercise can isolate peripheral effects related to postexercise vasodilation, it may provide insight into possible mechanisms behind this diurnal variation. METHODS: The study was conducted in ten healthy (5F, 5M) young individuals, following single-leg dynamic knee-extension exercise performed in the Morning (7:30-11:30 am) or the Evening (5-9 pm) on two different days, in random order. Arterial pressure (automated auscultation) and leg blood flow (femoral artery Doppler ultrasound) were measured pre-exercise and during 120 min postexercise. Net effect for each session was calculated as percent change in blood flow (or vascular conductance) between the Active Leg and the Inactive Leg. RESULTS: Following Morning exercise, blood flow was 34.9 ± 8.9% higher in the Active Leg versus the Inactive Leg (p < 0.05) across recovery. Following Evening exercise, blood flow was 35.0 ± 8.8% higher in the Active Leg versus the Inactive Leg (p < 0.05). Likewise, vascular conductance was higher in the Active Leg versus the Inactive Leg (Morning: +35.1 ± 9.0%, p < 0.05; Evening: +33.2 ± 8.2%, p < 0.05). Morning and Evening blood flow (p = 0.66) and vascular conductance (p = 0.64) did not differ. CONCLUSION: These data suggest previous studies which identified diurnal variations in postexercise vasodilation responses are likely reflecting central rather than peripheral modulation of cardiovascular responses.

Histamine-Receptor Antagonists Slow 10-km Cycling Performance in Competitive Cyclists.

Histamine is released within skeletal muscle during exercise. In humans, antihistamines have no effect on speed, power output, or time-to-completion of short-duration high-intensity exercise. In mice, blocking histamine's actions decreases speed and duration of endurance tasks. It is unknown if these opposing outcomes are the result of differences in histamine's actions between species or are related to duration and/or intensity of exercise, as blocking histamine during endurance exercise has not been examined in humans. PURPOSE: Determine the effects of histamine-receptor antagonism on cycling time trial performance in humans, with and without a preceding bout of sustained steady-state exercise. METHODS: Eleven (3F) competitive cyclists performed six 10-km time trials on separate days. The first two time trials served as familiarization. The next four time trials were performed in randomized-block order, where two were preceded by 120 min of seated rest (rest) and two by 120 min of cycling exercise (Exercise) at 50% V˙O2peak. Within each block, subjects consumed either combined histamine H1 and H2 receptor antagonists (Blockade) or Placebo, before the start of the 120-min Rest/Exercise. RESULTS: Blockade had no discernible effects on hemodynamic or metabolic variables during Rest or Exercise. However, Blockade increased time-to-completion of the 10-km time trial compared with Placebo (+10.5 ± 3.7 s, P < 0.05). Slowing from placebo to blockade was not different between rest (+8.7 ± 5.2 s) and Exercise (+12.3 ± 5.8 s, P = 0.716). CONCLUSIONS: Exercise-related histaminergic signaling appears inherent to endurance exercise and may play a role in facilitating optimal function during high-intensity endurance exercise.

Mast cell degranulation and de novo histamine formation contribute to sustained postexercise vasodilation in humans.

In humans, acute aerobic exercise elicits a sustained postexercise vasodilation within previously active skeletal muscle. This response is dependent on activation of histamine H1 and H2 receptors, but the source of intramuscular histamine remains unclear. We tested the hypothesis that interstitial histamine in skeletal muscle would be increased with exercise and would be dependent on de novo formation via the inducible enzyme histidine decarboxylase and/or mast cell degranulation. Subjects performed 1 h of unilateral dynamic knee-extension exercise or sham (seated rest). We measured the interstitial histamine concentration and local blood flow (ethanol washout) via skeletal muscle microdialysis of the vastus lateralis. In some probes, we infused either α-fluoromethylhistidine hydrochloride (α-FMH), a potent inhibitor of histidine decarboxylase, or histamine H1/H2-receptor blockers. We also measured interstitial tryptase concentrations, a biomarker of mast cell degranulation. Compared with preexercise, histamine was increased after exercise by a change (Δ) of 4.2 ± 1.8 ng/ml (P < 0.05), but not when α-FMH was administered (Δ-0.3 ± 1.3 ng/ml, P = 0.9). Likewise, local blood flow after exercise was reduced to preexercise levels by both α-FMH and H1/H2 blockade. In addition, tryptase was elevated during exercise by Δ6.8 ± 1.1 ng/ml (P < 0.05). Taken together, these data suggest that interstitial histamine in skeletal muscle increases with exercise and results from both de novo formation and mast cell degranulation. This suggests that exercise produces an anaphylactoid signal, which affects recovery, and may influence skeletal muscle blood flow during exercise.NEW & NOTEWORTHY Blood flow to previously active skeletal muscle remains elevated following an acute bout of aerobic exercise and is dependent on activation of histamine H1 and H2 receptors. The intramuscular source of histamine that drives this response to exercise has not been identified. Using intramuscular microdialysis in exercising humans, we show both mast cell degranulation and formation of histamine by histidine decarboxylase contributes to the histamine-mediated vasodilation that occurs following a bout of aerobic exercise.

A single dose of histamine-receptor antagonists before downhill running alters markers of muscle damage and delayed-onset muscle soreness.

Histamine contributes to elevations in skeletal muscle blood flow following exercise, which raises the possibility that histamine is an important mediator of the inflammatory response to exercise. We examined the influence of antihistamines on postexercise blood flow, inflammation, muscle damage, and delayed-onset muscle soreness (DOMS) in a model of moderate exercise-induced muscle damage. Subjects consumed either a combination of fexofenadine and ranitidine (blockade, n = 12) or nothing (control, n = 12) before 45 min of downhill running (-10% grade). Blood flow to the leg was measured before and throughout 120 min of exercise recovery. Markers of inflammation, muscle damage, and DOMS were obtained before and at 0, 6, 12, 24, 48, and 72 h postexercise. At 60 min postexercise, blood flow was reduced ~29% with blockade compared with control (P < 0.05). Markers of inflammation were elevated after exercise (TNF-ɑ, IL-6), but did not differ between control and blockade. Creatine kinase concentrations peaked 12 h after exercise, and the overall response was greater with blockade (18.3 ± 3.2 kU·l-1·h-1) compared with control (11.6 ± 2.0 kU·l-1·h-1; P < 0.05). Reductions in muscle strength in control (-19.3 ± 4.3% at 24 h) were greater than blockade (-7.8 ± 4.8%; P < 0.05) and corresponded with greater perceptions of pain/discomfort in control compared with blockade. In conclusion, histamine-receptor blockade reduced postexercise blood flow, had no effect on the pattern of inflammatory markers, increased serum creatine kinase concentrations, attenuated muscle strength loss, and reduced pain perception following muscle-damaging exercise.NEW & NOTEWORTHY Histamine appears to be intimately involved with skeletal muscle during and following exercise. Blocking histamine's actions during muscle-damaging exercise, via common over-the-counter antihistamines, resulted in increased serum creatine kinase, an indirect marker of muscle damage. Paradoxically, blocking histamine's actions attenuated muscle strength loss and reduced perceptions of muscle pain for 72 h following muscle-damaging exercise. These results indicate that exercise-induced histamine release may have a broad impact on protecting muscle from exercise-induced damage.

Post-exercise syncope: Wingate syncope test and visual-cognitive function.

Adequate cerebral perfusion is necessary to maintain consciousness in upright humans. Following maximal anaerobic exercise, cerebral perfusion can become compromised and result in syncope. It is unknown whether post-exercise reductions in cerebral perfusion can lead to visual-cognitive deficits prior to the onset of syncope, which would be of concern for emergency workers and warfighters, where critical decision making and intense physical activity are combined. Therefore, the purpose of this experiment was to determine if reductions in cerebral blood velocity, induced by maximal anaerobic exercise and head-up tilt, result in visual-cognitive deficits prior to the onset of syncope. Nineteen sedentary to recreationally active volunteers completed a symptom-limited 60° head-up tilt for 16 min before and up to 16 min after a 60 sec Wingate test. Blood velocity of the middle cerebral artery was measured using transcranial Doppler ultrasound and a visual decision-reaction time test was assessed, with independent analysis of peripheral and central visual field responses. Cerebral blood velocity was 12.7 ± 4.0% lower (mean ± SE; P < 0.05) after exercise compared to pre-exercise. This was associated with a 63 ± 29% increase (P < 0.05) in error rate for responses to cues provided to the peripheral visual field, without affecting central visual field error rates (P = 0.46) or decision-reaction times for either visual field. These data suggest that the reduction in cerebral blood velocity following maximal anaerobic exercise contributes to visual-cognitive deficits in the peripheral visual field without an apparent affect to the central visual field.

Evidence of a broad histamine footprint on the human exercise transcriptome.

KEY POINTS: Histamine is a primordial signalling molecule, capable of activating cells in an autocrine or paracrine fashion via specific cell surface receptors, in a variety of pathways that probably predate its more recent role in innate and adaptive immunity. Although histamine is normally associated with pathological conditions or allergic and anaphylactic reactions, it may contribute beneficially to the normal changes that occur within skeletal muscle during the recovery from exercise. We show that the human response to exercise includes an altered expression of thousands of protein-coding genes, and much of this response appears to be driven by histamine. Histamine may be an important molecular transducer contributing to many of the adaptations that accompany chronic exercise training. ABSTRACT: Histamine is a primordial signalling molecule, capable of activating cells in an autocrine or paracrine fashion via specific cell surface receptors. In humans, aerobic exercise is followed by a post-exercise activation of histamine H1 and H2 receptors localized to the previously exercised muscle. This could trigger a broad range of cellular adaptations in response to exercise. Thus, we exploited RNA sequencing to explore the effects of H1 and H2 receptor blockade on the exercise transcriptome in human skeletal muscle tissue harvested from the vastus lateralis. We found that exercise exerts a profound influence on the human transcriptome, causing the differential expression of more than 3000 protein-coding genes. The influence of histamine blockade post-exercise was notable for 795 genes that were differentially expressed between the control and blockade condition, which represents >25% of the number responding to exercise. The broad histamine footprint on the human exercise transcriptome crosses many cellular functions, including inflammation, vascular function, metabolism, and cellular maintenance.

Neurovascular control following small muscle-mass exercise in humans.

Sustained postexercise vasodilation, which may be mediated at both a neural and vascular level, is seen in previously active skeletal muscle vascular beds following both large and small muscle-mass exercise. Blunted sympathetic vascular transduction and a downward resetting of the arterial baroreflex contribute to this vasodilation after cycling (large muscle-mass exercise), but it is unknown if these responses also contribute to sustained vasodilation following small muscle-mass exercise. This study aimed to determine if baroreflex sensitivity is altered, the baroreflex is reset, or if sympathetic vascular transduction is blunted following small muscle-mass exercise. Eleven healthy, college-aged subjects (five males, six females) completed one-leg dynamic knee-extension exercise for 1 h at 60% of peak power output. While cardiovagal baroreflex sensitivity was increased ~23% postexercise relative to preexercise (P < 0.05), vascular and integrated baroreflex sensitivity were not altered following exercise (P = 0.31 and P = 0.48). The baroreflex did not exhibit resetting (P > 0.69), and there was no evidence of changes in vascular transduction following exercise (P = 0.73). In conclusion, and in contrast to large muscle-mass exercise, it appears that small muscle-mass exercise produces a sustained postexercise vasodilation that is largely independent of central changes in the baroreflex.

Effect of antioxidants on histamine receptor activation and sustained postexercise vasodilatation in humans.

NEW FINDINGS: What is the central question of this study? Is exercise-induced oxidative stress the upstream exercise-related signalling mechanism that leads to sustained postexercise vasodilatation via activation of H1 and H2 histamine receptors? What is the main finding and its importance? Systemic administration of the antioxidant ascorbate inhibits sustained postexercise vasodilatation to the same extent as seen previously with H1 and H2 histamine receptor blockade following small muscle-mass exercise. However, ascorbate has a unique ability to catalyse the degradation of histamine. We also found that systemic infusion of the antioxidant N-acetylcysteine had no effect on sustained postexercise vasodilatation, suggesting that exercise-induced oxidative stress does not contribute to sustained postexercise vasodilatation. An acute bout of aerobic exercise elicits a sustained postexercise vasodilatation that is mediated by histamine H1 and H2 receptor activation. However, the upstream signalling pathway that leads to postexercise histamine receptor activation is unknown. We tested the hypothesis that the potent antioxidant ascorbate would inhibit this histaminergic vasodilatation following exercise. Subjects performed 1 h of unilateral dynamic knee extension at 60% of peak power in three conditions: (i) control; (ii) i.v. ascorbate infusion; and (iii) ascorbate infusion plus oral H1 /H2 histamine receptor blockade. Femoral artery blood flow was measured (using Doppler ultrasound) before exercise and for 2 h postexercise. Femoral vascular conductance was calculated as flow/pressure. Postexercise vascular conductance was greater for control conditions (3.4 ± 0.1 ml min(-1) mmHg(-1) ) compared with ascorbate (2.7 ± 0.1 ml min(-1) mmHg(-1) ; P < 0.05) and ascorbate plus H1 /H2 blockade (2.8 ± 0.1 ml min(-1) mmHg(-1) ; P < 0.05), which did not differ from one another (P = 0.9). Given that ascorbate may catalyse the degradation of histamine in vivo, we conducted a follow-up study, in which subjects performed exercise in two conditions: (i) control; and (ii) i.v. N-acetylcysteine infusion. Postexercise vascular conductance was similar for control (4.0 ± 0.1 ml min(-1) mmHg(-1) ) and N-acetylcysteine conditions (4.0 ± 0.1 ml min(-1) mmHg(-1) ; P = 0.8). Thus, the results in the initial study were due to the degradation of histamine in skeletal muscle by ascorbate, because the histaminergic vasodilatation was unaffected by N-acetylcysteine. Overall, exercise-induced oxidative stress does not appear to contribute to sustained postexercise vasodilatation.

Blood pressure regulation X: what happens when the muscle pump is lost? Post-exercise hypotension and syncope.

Syncope which occurs suddenly in the setting of recovery from exercise, known as post-exercise syncope, represents a failure of integrative physiology during recovery from exercise. We estimate that between 50 and 80% of healthy individuals will develop pre-syncopal signs and symptoms if subjected to a 15-min head-up tilt following exercise. Post-exercise syncope is most often neurally mediated syncope during recovery from exercise, with a combination of factors associated with post-exercise hypotension and loss of the muscle pump contributing to the onset of the event. One can consider the initiating reduction in blood pressure as the tip of the proverbial iceberg. What is needed is a clear model of what lies under the surface; a model that puts the observational variations in context and provides a rational framework for developing strategic physical or pharmacological countermeasures to ultimately protect cerebral perfusion and avert loss of consciousness. This review summarizes the current mechanistic understanding of post-exercise syncope and attempts to categorize the variation of the physiological processes that arise in multiple exercise settings. Newer investigations into the basic integrative physiology of recovery from exercise provide insight into the mechanisms and potential interventions that could be developed as countermeasures against post-exercise syncope. While physical counter maneuvers designed to engage the muscle pump and augment venous return are often found to be beneficial in preventing a significant drop in blood pressure after exercise, countermeasures that target the respiratory pump and pharmacological countermeasures based on the involvement of histamine receptors show promise.

A retrospective cohort study on the influence of UV index and race/ethnicity on risk of stress and lower limb fractures.

BACKGROUND: Low vitamin D status increases the risk of stress fractures. As ultraviolet (UV) light is required for vitamin D synthesis, low UV light availability is thought to increase the risk of vitamin D insufficiency and poor bone health. The purpose of this investigation was to determine if individuals with low UV intensity at their home of record (HOR) or those with darker complexions are at increased risk of developing stress fractures and lower limb fractures during U.S. Army Basic Combat Training (BCT). METHODS: This was a retrospective cohort study using the Armed Forces Health Surveillance Center data repository. All Basic trainees were identified from January 1997 to January 2007. Cases were recruits diagnosed with stress fractures and lower limb fractures during BCT. The recruit's home of record (HOR) was identified from the Defense Manpower Data Center database. The average annual UV intensity at the recruits' HOR was determined using a U.S National Weather Service database and recruits were stratified into low (≤3.9); moderate (4.0-5.4), and high (≥5.5) UV index regions. Race was determined from self-reports. RESULTS: The dataset had 421,461 men and 90,141 women. Compared to men, women had greater risk of developing stress fractures (odds ratio (OR) = 4.5, 95% confidence interval (95%CI) = 4.4-4.7, p < 0.01). Contrary to the hypothesized effect, male and female recruits from low UV index areas had a slightly lower risk of stress fractures (male OR (low UV/high UV) = 0.92, 95%CI = 0.87-0.97; females OR = 0.89, 95%CI = 0.84-0.95, p < 0.01) and were at similar risk for lower limb fractures (male OR = 0.98, 95%CI = 0.89-1.07; female OR = 0.93, 95%CI = 0.80-1.09) than recruits from high UV index areas. Blacks had lower risk of stress and lower limb fractures than non-blacks, and there was no indication that Blacks from low UV areas were at increased risk for bone injuries. CONCLUSIONS: The UV index at home of record is not associated with stress or lower limb fractures in BCT. These data suggest that UV intensity is not a risk factor for poor bone health in younger American adults.

The effect of heat acclimation on sweat microminerals: artifact of surface contamination.

UNLABELLED: Heat acclimation (HA) reportedly conveys conservation in sweat micromineral concentrations when sampled from arm sweat, but time course is unknown. The observation that comprehensive cleaning of the skin surface negates sweat micromineral reductions during prolonged sweating raises the question of whether the reported HA effect is real or artifact of surface contamination. PURPOSE: To measure sweat mineral concentrations serially during HA and determine if surface contamination plays a role in the reported mineral reductions. METHODS: Calcium (Ca), copper (Cu), magnesium (Mg), and zinc (Zn) were measured in sweat obtained from 17 male volunteers using an arm bag on Day 1, 5, and 10 of a HA protocol. To study the role of contamination, sweat was simultaneously (n = 10 subjects) sampled twice daily from a cleaned site (WASH) and unclean site (NO WASH) on the scapular surface. RESULTS: Sweat Ca, Cu, and Mg from Arm Bag trended progressively downward from Day 1 to Day 10 of HA (p = .10-0.25). Micromineral concentrations from the WASH site did not change between Day 1, 5, or 10 (Ca = 0.30 ± 0.12 mmol/L, Cu 0.41 ± 0.53 µmol/L; Zn 1.11 ± 0.80 µmol/L). Surface contamination can confound sweat mineral estimates, as sweat Ca and Cu from NO WASH site were initially higher than WASH (p < .05) but became similar to WASH when sampled serially. CONCLUSION: Heat acclimation does not confer reductions in sweat Ca, Cu, Mg, or Zn. When the skin surface is not cleaned, mineral residue inflates initial sweat mineral concentrations. Earlier reports of micromineral reductions during HA may have been confounded by interday cleaning variability.