Despite the critical importance of blood flow for bone, mechanisms regulating bone vasculature are poorly understood. Myogenic vasoconstriction is an important regulatory mechanism that is engaged in most daily activities, but our understanding primarily derives from animal work and/or other vascular beds. In young healthy adults, we employed two levels of leg dependency to engage myogenic vasoconstriction. We measured tibial blood content via near‐infrared spectroscopy (total hemoglobin, ΔtHb) and contrasted it to whole leg flow via popliteal blood flow velocity (LBV) via Doppler ultrasound. Myogenic vasoconstriction was engaged by lowering the leg below heart level (supine to upright to dependent), resulting in increased leg perfusion pressure as assessed by brachial mean pressure adjusted for the hydrostatic pressure from the heart to the tibia. Increased leg perfusion pressure in both positions (Δ30.1 ± 1.36 and Δ42.1 ± 1.16 mmHg; p < 0.01) was accompanied by graded declines in LBV (Δ‐1.88 ± 0.21 and Δ‐2.98 ± 0.27 cm/(s*beat); p < 0.01), indicating whole limb myogenic vasoconstriction. Tibial hemoglobin content did not change (ΔtHb: −0.28 ± 1.76 and 1.26 ± 2.33 μM; p > 0.5), indicating myogenic vasoconstriction was evident, but of lower magnitude compared to the whole leg. These results indicate that myogenic vasoconstriction plays an active role in regulating the tibial vasculature, but with a less robust response compared to the whole leg.

Abstract 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.

Summary 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.

Individuals with spinal cord injuries (SCI) have a greater incidence of Type 2 Diabetes (T2D) than their non-injured peers. The increased incidence of T2D has been noted in individuals within the first few years after injury, and incidence increases with time since injury. Aerobic exercise training improves long-term glycemic control in non-injured individuals and results in improved glycemic control in individuals with chronic SCI (>10 years). However, it is unknown whether individuals with acute injuries (<3 years) display altered glucose control, and if aerobic training may prevent worsening of glucose control and T2D. Therefore, we assessed blood glucose regulation in individuals <3 years post SCI injury. Glucose regulation was assessed through fasting blood glucose, insulin, hemoglobin A1C (HbA1C), homeostatic model assessment for insulin resistance (HOMA-IR), and an oral glucose tolerance test (OGTT). In addition, body composition was estimated via dual energy x-ray absorptiometry. These assessments were made prior to, and following 3- and 6-months (mo) of aerobic exercise training consisting of hybrid functional electrical stimulation rowing. Data were analyzed with 1-way RMANOVA. Eight individuals (1F, 7M, age 20-45 years) with SCI 9-27 mo post-injury and a neurological level of injury from spinal cord segments C3 to T3 were enrolled. Individuals exercised for 30min per session, at ~60% VO2peak, 2-3 times per week. Fasting glucose (Pre:85±9, 3m:88±8, 6m:86±2 mg/dL, p=0.55), insulin (Pre:6.0±3.8, 3m:5.7±2.5, 6m:3.9±2.5 uIU/mL, p=0.25), HbA1C (Pre:4.9±0.3, 3m:5.0±0.3, 6m:4.8±0.1%, p=0.73) and HOMA-IR (Pre:1.4±1.0, 3m:1.2±0.7, 6m:0.7±0.4, p=0.26) did not change after 6-mo of training. In contrast, the dynamic assessment of glucose tolerance (OGTT) showed dramatic worsening (AUC Pre:15.7±3.8, 3m:17.8±5.9, 6m:17.6±5.8 units, p=0.04) from pre-exercise to 3-mo. Moreover, following 6-mo of exercise training, 1 individual met the diagnostic criteria for impaired glucose tolerance and another 2 for diabetes. Exercise training did not change visceral adipose mass (Pre:1.4±0.9, 3m:1.4±1.2, 6m:1.3±1.2 kg, p=0.96) or total body lean mass (Pre:50.4±9.5, 3m:49.6±9.6, 6m:49.5±9.5kg, p=0.98). These results suggest that fasting measures alone are not sensitive enough in detecting impairments in glucose metabolism in the acute period following a SCI. Interestingly, in people with SCI, whole-body aerobic exercise does not prevent the occurrence of impaired glucose metabolism. The worsening of glucose tolerance occurs despite a conservation of lean mass and no increase in visceral adiposity. It will be of importance to determine the mechanisms underlying the worsening of glycemic control and develop therapies to prevent metabolic disease in SCI. R01 HL117037, F32 HL156675 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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.

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.

Despite the critical importance of sufficient and well-regulated blood flow supply for bone health, regulation of bone blood flow in humans remains poorly understood. We have recently shown that sympathetic and myogenic control have active roles in regulating blood flow to tibial bone in humans. Responses are smaller and delayed in the tibia compared to the whole leg, underscoring the importance of directly interrogating mechanisms underlying bone blood flow control. Nitric oxide (NO) mediated vasodilation is another important regulatory mechanism and studies to date have been confined to assessment of whole limb blood flow responses that primarily reflect muscle. In young healthy individuals (N=8), we characterized NO-mediated vasodilation in tibial blood flow and contrasted it to whole leg blood flow. We employed sublingual nitroglycerin (0.4 mg) as an NO donor. We obtained a 5 min resting baseline, followed by the responses to sublingual nitroglycerin for 10 min in supine subjects. Tibial blood flow was measured continuously via near infrared spectroscopy as total hemoglobin (Hb) and whole leg blood flow as popliteal Doppler flow velocity in the same leg. NO-mediated vasodilation was characterized by peak response, time to peak response, and time to return to baseline over the 10 min response. Tibial blood flow (total Hb) increased rapidly in response to nitroglycerin reaching a maximum of 1.61 ± 0.69 μM after 3.5 min. Afterwards, total Hb steadily declined, returning to baseline values by 10 min. Whole leg blood flow increased at a slower rate reaching a maximum of 7.12 ± 2.72 cm/s after 4.5 min. However, whole leg blood flow remained elevated throughout the entire 10 min measurement. Our results indicate that similar to other vascular beds, bone vasculature has a robust NO-mediated vasodilation, but appears to be faster and shorter lasting compared to the whole leg vasculature. This is not dissimilar from our previous findings indicating different time characteristic time-courses of response to other vascular controllers in tibial bone compared with whole leg vasculature. Paralyzed Veterans of America Research Foundation (AED), NIH NIAMS R21 AR074054 (JAT) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Following a spinal cord injury (SCI), vascular remodeling occurs below the level of injury, including reductions in arterial diameter, anterograde and retrograde blood flow (BF), oscillatory shear stress, and endothelial function. Moderate-intensity aerobic exercise and passive heating produce increases in anterograde BF and SS that are associated with improved endothelial function in able-bodied (AB) individuals, but it is unknown if similar changes occur in individuals with SCI. PURPOSE: To compare oscillatory BF and shear stress following aerobic exercise and passive heating in the lower leg of individuals with SCI and AB individuals. METHODS: Volunteers performed three randomized trials ~7 days apart. Two trials consisted of 25 min of rowing (AB), or functional electrical stimulation rowing (SCI) followed by 45 min of either lower leg immersion in hot (42 °C) or temperate (36 °C) water. The third trial was 45 min of leg immersion in 42 °C. Popliteal artery diameter, BF (anterograde, retrograde), and oscillatory shear index (OSI) were measured on the right leg at rest, after exercise, and during leg immersion. RESULTS: Eight individuals participated (3 SCI, 1F 2M; 5 AB, 4F 1M). SCI had lower resting OSI (0.12 ± 0.14) than AB (0.20 ± 0.07; p = 0.04) due to smaller anterograde (SCI:12.8 ± 12.8, AB:33.2 ± 19.8 ml min-1; p = 0.01) and retrograde BF (SCI:0.92 ± 1.2, AB:8.8 ± 6.2 ml min-1, p < 0.01). After exercise, OSI decreased in AB (Δ-0.06 ± 0.05) and increased in SCI (Δ + 0.12 ± 0.14; p < 0.01) due to 1) larger increase in anterograde BF in AB (Δ21.9 ± 13.0 ml min-1) than SCI (Δ1.6 ± 1.6 ml min-1), and 2) reduction in retrograde BF in AB (Δ-0.4 ± 1.1 ml min-1) and an increase in SCI (Δ + 1.4 ± 0.8 ml min-1). Lower leg immersion in 36 °C water did not change OSI in AB or SCI (Δ0.06 ± 0.03; p = 0.75). OSI decreased similarly with 42 °C water immersion with or without prior exercise and this was driven by an increase in anterograde BF in AB (Δ219.8 ± 43.6 ml min-1) that was larger than SCI (Δ33.4 ± 16.2, p < 0.01). CONCLUSION: Blood flow and shear stress responses to exercise and passive heating are smaller in individuals with SCI than AB. Importantly, in SCI passive heating produced larger changes in BF and OSI than exercise. Therefore, passive heating is a potential therapy to supplement exercise to improve endothelial health in individuals with SCI.

Individuals with spinal cord injuries (SCI) have a greater incidence of cardiovascular disease (CVD) than the non-injured. Contributing to the increased CVD is decreased cardiometabolic health including increased insulin resistance, central adiposity, and dyslipidemia. In fact, cross-sectional analyses of individuals with chronic SCI (up to 50 years post injury) indicates that up to 70% are classified as overweight/obese and 25-60% have either insulin resistance or dyslipidemia. However, current understanding of cardiometabolic health in SCI derives from those with chronic injury, hence it is unknown if biomarkers are adversely affected in those with more acute injuries. Therefore, we assessed cardiometabolic health in individuals with SCI <3 yrs. Cardiometabolic health was assessed through fasting blood glucose, insulin, triglycerides, low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol, C-reactive protein (CRP), and hemoglobin A1C (HbA1C). In addition, oral glucose tolerance testing (OGTT) was performed, and body composition was estimated via dual energy x-ray absorptiometry (DXA). Five individuals (1F, 4M) aged 20 to 34 yo with SCI at neurologic level of injury ranging from spinal cord segments C6 to T4 (ASIA A and B) at 9 to 27 months post-injury participated. All subjects displayed at ≥1 marker of impaired cardiometabolic health, while one displayed five markers. Body fat ranged from 27 to 42%, and one subject was classified as obese, two as overweight, and two as normal weigh based on BMI. Dyslipidemia was prominent in four of five subjects: one had elevated total cholesterol (>200 mg/dL), one had elevated triglycerides (>150 mg/dL), three had low HDL (<40 mg/dL), and two had elevated LDL (>100 mg/dL). Glucose tolerance test data and fasting insulin measurements showed normal fasting glucose (<100 mg/dl), HOMA-IR (<2.0), and HbA1C (<5.7%) in all individuals, but one subject displayed impaired glucose tolerance during the OGTT (1 hr post >200 mg/dL, 2hr post >180 mg/dL). Three of five subjects had CRP levels >3.0, suggesting an increased inflammatory state. These preliminary results strongly suggest that cardiometabolic health may be impaired within 3 years after SCI. These biomarkers of altered cardiometabolic health, specifically related to lipid dysregulation, may reflect adipose tissue dysfunction, possibly in response to the accumulation of adipose tissue and/or the decreased physical activity, increased sedentary activity, and skeletal muscle atrophy that typically occurs following a spinal injury. More research is needed to determine the mediators of impaired cardiometabolic health in subjects with SCI and determine effective strategies to mitigate the detrimental effects of SCI on cardiometabolic health.

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.

Bone health is critically dependent on adequate blood flow supplied by its extensive vascular network. Without adequate perfusion to provide oxygen and essential nutrients critical for bone metabolism, nearly all skeletal functions are compromised. However, despite the importance of blood flow to bone, regulation of bone blood flow is poorly understood in humans. The broad hypothesis of the current work is that the primary regulators of blood flow to bone are not different from other vascular beds. We have recently shown that sympathetic innervation of the bone vasculature has an active role in controlling bone blood flow in young healthy individuals. This work furthers our previous findings by investigating additional key bone blood flow regulators - myogenic vasodilation and vasoconstriction. While vascular myogenic control has been investigated in soft tissue, to our knowledge there has been no research in the bone vasculature in humans, with only a handful of animal studies. In young healthy individuals (N=8), we characterized myogenic control of tibial blood flow via novel custom-made near infrared spectroscopy (NIRS). Tibial blood flow via NIRS was measured as oxy-, deoxy-, and total hemoglobin (Hb). We employed reactive hyperemia and leg dependency to assess myogenic vasodilation and vasoconstriction in the whole calf and in the tibia. The magnitude of maximum myogenic vasodilation was defined by the peak reactive blood flow response to sustained ischemia. Arterial flow to the lower leg was occluded by rapidly inflating a pneumatic thigh cuff above the knee to 220 mmHg in supine subjects. Tibial blood flow was assessed via NIRS and whole leg blood flow velocity in the popliteal artery of the same leg was measured via Doppler ultrasound during 1 min of rest, 10 min of cuff inflation, and 5 min of recovery. Myogenic vasoconstriction was assessed via leg dependency, i.e., during two levels of increased transmural pressure achieved by lowering the leg below heart level. Only tibial blood flow was assessed during 5 min in supine position, 5 min in seated upright position, and 5 min in seated position with legs lowered at 90deg knee flexion. During cuff occlusion, there was a time dependent decrease in bone oxyHb accompanied by an increase in deoxyHb indicating lack of flow with continued metabolism. Tibial total Hb (sum of oxy- and deoxy-Hb) did not change significantly during cuff inflation, but increased rapidly and markedly with cuff release, far surpassing baseline values when flow was restored. A similar overshoot response was seen in whole leg blood flow with cuff release. Thus, the response of tibial flow to reactive hyperemia follows the same behavior as the whole limb, indicating an active myogenic vasodilator response in bone similar to other vascular beds. During leg dependency, despite increases in arterial perfusion pressure at both levels (ΔP, 25.8 + 3.67, and 40.0 + 3.02 mmHg), there was no change in tibial flow (total Hb, -0.39 + 7.40, and -0.29 + 16.2 μM). Hence, unchanged tibial flow despite increased pressure indicates a compensatory vasoconstrictor response in the tibia. Our results indicate that similar to other vascular beds, myogenic control plays an active role in regulating the bone vasculature in young healthy individuals. Characterizing blood flow regulation in bone constitutes the basis of defining its role in overall bone health and its contribution to numerous bone loss conditions.

Smaller heart structures and reduced cardiac function are documented in cross‐sectional comparisons of individuals with spinal cord injury (SCI) and age/weight matched able bodied controls. The smaller heart structures and reduced function may result from progressive cardiac atrophy similar to that observed with diminished physical activity, extended periods of bed rest, and space flight. It is unknown if there is progressive cardiac atrophy in the months following SCI. Additionally, slightly larger hearts and greater retention of function are found in individuals with thoracic compared to cervical injuries, suggesting that the level of spinal injury may differentially affect reductions in heart structure and function after SCI. Therefore, the purpose of this research was to 1) quantify cardiac structure and function of individuals within the first 24 months after injury, 2) identify the relationship between cardiac structure and function and time since injury, and 3) examine injury level’s effect on heart structure/function and time since injury. A cross‐sectional assessment of cardiac structure and function was made using transthoracic echocardiography (Vivid‐Q; GE Healthcare) on twenty‐nine (4F) volunteers who were 3‐ to 24‐months post‐injury. Myocardial structure and function were assessed using 2D, speckle‐tracking, and tissue Doppler in accordance with contemporary clinical echocardiographic guidelines. Heart rate and blood pressures were assessed simultaneously using a combination of a standard lead II electrocardiogram (ECG) and brachial oscillometric blood pressure monitor (Dash 5000 patient monitor, GE). The relationship between cardiac structure/function and time since injury were analyzed using linear regression. Neurological and sensory level of injury were entered into the model as covariates to determine whether or not the relationships differed with time since injury. Time since injury was most strongly associated with a reduction in left ventricular end‐diastolic volume (Δ= −2.07±0.70 ml·mo −1 , r 2 =0.266, p=0.007), end‐systolic volume (Δ= −1.05±0.38 ml·mo −1 , r 2 =0.237, p=0.012), and left ventricular mass (Δ= −3.0 ± 1.2 g·mo −1, r 2 =0.192, p=0.018). These changes in left ventricular structure were paralleled by a reduced stroke volume (Δ= −1.03±0.50 ml·mo −1 , r 2 =0.154 p=0.048) and cardiac output (Δ= −0.12±0.04 L·min −1 ·mo −1 , r 2 =0.322, p=0.002). There were no significant associations of blood pressures, wall thickness, or measures of diastolic function with time since injury (p>0.050). The reductions in left ventricular structure and systolic function were not differentially affected by neurological or sensory level of injury (p= 0.412–0.973). These results suggest there are gradual reductions in left ventricular structure and systolic function over the 24 months following spinal cord injury which are not affected by the neurological or sensory level of injury. Although there is loss of left ventricular structure and function, blood pressure appears maintained suggesting peripheral compensatory adjustments. This information indicates that cardiac rehabilitation interventions should occur relatively soon after spinal cord injury to mitigate cardiac atrophy. Support or Funding Information Funded by NIH Grant (R01‐HL‐117037) and The Spaulding Research Institute Leadership Catalyst

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.

One of the physiological changes following moderate intensity aerobic exercise is a transient reduction in blood pressure, termed post‐exercise hypotension (PEH), which is exercise intensity and duration dependent. This short‐term reduction in blood pressure is dependent upon skeletal muscle histamine production and release, which causes increased conductance via local activation of histamine H1 and H2 receptors. PEH is abolished when antihistamines are consumed prior to exercise. Additionally, histamine‐receptor antagonism during a single bout of exercise modifies expression of the transcriptome related to inflammation, angiogenesis, and metabolism. Due to the large role histamine plays in post‐exercise recovery, the scope of histamine receptor activation in adaptations to aerobic exercise training needs to be determined. Therefore, the purpose of this study was to examine histamine’s role in promoting adaptation to exercise. It is hypothesized that blocking histamine’s actions will attenuate adaptations that occur from aerobic exercise training. 16 young, healthy, recreationally active individuals (5M, 11F) volunteered for this study. All volunteers completed 6 weeks of exercise training (3–4 times a week), for a total of 21 exercise sessions. Exercise training combined 18 sessions of continuous exercise (1 hour at 60% VO2peak) and 3 sessions of high intensity interval training (30 min between 30 and 90% VO2peak). Volunteers were randomly placed into a placebo or histamine antagonism (540 mg fexofenadine; a H1‐receptor antagonist, and 300 mg of ranitidine; a H2‐receptor antagonist) group, and consumed medication 1 hour prior to each exercise session. Data was collected 4 times throughout the study with pre and post exercise training measures, as well as after every 2 weeks of exercise training. Measurements of VO2peak and cycle ergometry work rate were obtained. Exercise training resulted in increased absolute VO2peak of all subjects (9.4±1.5%; P<0.01); however, no difference was seen between groups (10.9±1.8% control vs 7.9±2.4% blockade; P=0.35). Additionally, exercise training resulted in increased cycle ergometry work rate of all subjects (11.2±1.6%; P<0.01); however, there was a trend for blunted improvement with blockade (7.7±2.4%) vs control (14.6±2.8%; P=0.08). In conclusion, blocking histamine’s actions had no effect on VO2 adaptations to exercise training. Additional information about factors related to O2 delivery and consumption are needed to understand the relationship between histamine and cardiovascular adaptation to exercise training.Support or Funding InformationSupport provided by: The Eugene & Clarissa Evonuk Memorial Graduate Fellowship

ABSTRACT Competitive runners seek to control as many performance variables as possible when preparing for peak competition. However, race day weather is out of an athlete's control and can have a profound impact on performance. This review defines hot weather in terms of running performance, details the physiology underlying heat-related performance decrements, and discusses strategies that may mitigate the negative impact of heat on cardiovascular strain and attenuate reductions in heat-related running performance.

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.

ABSTRACT 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˙O 2peak . Within each block, subjects consumed either combined histamine H 1 and H 2 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.

Histamine‐receptor antagonists (“antihistamines”) are widely used among endurance athletes and are not currently banned by the World Anti‐Doping Agency. Our lab has recently shown that a single dose of antihistamines prior to muscle‐damaging exercise attenuates strength loss and muscle pain in the 72 hours following exercise. Histamine, produced within muscle, may be a factor in exercise‐induced muscle pain/discomfort and, therefore, perception of effort, as group III/IV muscle afferents (nociceptive neurons) are sensitized via activation of H1 and H2 receptors. Histamine may have more influence on muscle pain and effort sensations during long‐duration exercise than short‐duration, because the activity of histidine decarboxylase (the enzyme that creates histamine) increases with exercise duration. Therefore, the purpose of this experiment was to determine if combination H1/H2 antihistamines increase endurance exercise performance. It was hypothesized that H1/H2 antihistamines would decrease the time to completion of a fixed‐distance time‐trial compared to placebo, and the effect would be greater following an endurance‐exercise bout. Eleven (3F) highly competitive cyclists (Cat 1–3) performed six 10 km time‐trials on separate days. The first two trials served as a familiarization, and repeatability was assessed by calculating a coefficient of variation (CV) between times to completion. The next 4 trials were performed in a randomized‐block order. Two were preceded by 120 min of seated rest and two by 120 min of steady‐state cycling at 50% VO2peak. Within those blocks, volunteers consumed either antihistamines (540 mg fexofenadine; a H1 receptor blocker, and 300 mg of ranitidine; a H2 blocker) or placebo 60 min prior to the start of rest/exercise. The main outcome variable was 10 km time to completion. Additionally, rating of perceived exertion (RPE), isometric quadriceps muscle strength, blood glucose, and blood lactate were measured prior to and following the time‐trials. Conventional statistics (2‐Way Repeated Measures ANOVA), effect size (ES = Cohen's dz), 95% CI, and CV from familiarization trials were used to determine the presence, strength, and meaningfulness of differences, respectively, between the trials. There was a significant reduction in performance with antihistamines compared to placebo (+10.5 ± 3.8 s, mean±SEM, drug effect p=0.002), the reduced performance tended to be exacerbated by prior exercise (p=0.057) but there was no drug by prior exercise interaction (p=0.716) (Figure 1). The day‐to‐day 10 km performance variability (CV) was 0.98%. The percent change between placebo and antihistamine was likely trivial for time‐trials following rest (mean −0.87%, 95%CI −2.02 to 0.29%) (ES=0.505) and potentially harmful following exercise (mean −1.2%, 95%CI −2.45 to 0.05%) (ES=0.646). There were no drug effects on changes (pre to post time‐trial) in isometric muscle strength (p=0.607), RPE (p=0.828), blood glucose (p=0.964) or lactate (p=0.402) between antihistamine and placebo conditions. Thus, contrary to our hypothesis, blocking histamine's receptors slowed performance of 10 km time‐trials in highly competitive cyclists and did not influence perception of effort.Support or Funding InformationEugene & Clarissa Evonuk Memorial Graduate FellowshipThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.