EXERCISE-INDUCED ELEVATIONS IN SKELETAL MUSCLE HISTAMINE CONTRIBUTES TO INCREASED POST-EXERCISE CAPILLARY PERMEABILITY

C.K. Edwards, M.R. Ely, D.C. Sieck, J.E. Mangum, E.A. Larson, J.R. Halliwill FACSM. University of Oregon. Eugene, OR Histamine, an endogenously released molecule in immune and inflammatory responses increases local vasodilation, blood flow, and capillary permeability. During exercise, histamine is produced within exercising muscle and contributes to an elevated post-exercise blood flow. The histamine-induced post-exercise vasodilation is contained within previously exercised muscle as histamine concentrations are not elevated in non-exercised muscle (i.e. arms during leg exercise). It is unknown if intramuscular histamine also contributes to elevate capillary permeability following exercise. PURPOSE: To compare capillary permeability of the leg before and after prolonged unilateral knee-extension exercise under normal conditions and when histaminergic signaling is blocked. It was hypothesized that H1/H2receptor antihistamines would decrease capillary permeability following exercise in an exercised leg but not in a resting leg. METHODS: Six (2F) volunteers performed 60 min of unilateral knee-extension exercise at 60% of peak power after consuming either Placebo or histamine (H1/H2) receptor antagonists (Blockade). A capillary filtration coefficient (CFC) reflecting the rate of change in limb girth per rise in venous pressure was calculated using venous occlusion plethysmography. A CFC was calculated prior to (PRE) and following (POST) exercise in both the exercised leg (EL) and the resting leg (RL). Data were analyzed with a 3-way RM ANOVA and presented as Means±SEM. RESULTS: On average, CFC increased 161±90% (PRE: 2.5±1.0 to POST: 6.6±2.3 μg·100g-1·min-1·mmHg-1) in the EL and 38±31% (PRE: 4.8 to POST: 6.5 μg·100g-1·min-1·mmHg-1) in the RL during Placebo. Blockade attenuated the exercise-induced rise in CFC in the EL to 13±41% (PRE = 4.3±1.3 to POST = 4.9±1.8 μg·100g-1·min-1·mmHg-1) and in the RL 2±45% (PRE: 3.8±1.4 to POST: 3.8±1.7 μg·100g-1·min-1·mmHg-1). Due to the high variability in the measures there was a trend for CFC to increase with exercise (P=0.161), for Blockade to attenuate the rise in CFC (P=0.363), and for a leg by drug interaction (P=0.289). CONCLUSION: These initial data suggest that exercise-induced histamine production contributes to the elevated CFC within exercised limbs. Support provided by: ACSM NW Student Research Award; O’Day Fellowship; Carol Carver Pay-it-Forward Thesis Gran

HISTAMINE RECEPTOR-MEDIATED SUSTAINED POST-EXERCISE VASODILATION IN YOUNG TRAINED AND UNTRAINED ADULTS

M.J. Luttrell, P.M. Abdala, M.R. Ely, D.C. Sieck, J.E. Mangum, J.R. Halliwill FACSM University of Oregon, Eugene, OR Histamine-mediated sustained post-exercise vasodilation in response to one hour of dynamic knee extension has been established in young, recreationally active adults. It is unknown whether endurance exercise training modifies this response in young adults. PURPOSE: The purpose of this study was to test the hypothesis that sedentary young adults have similar histamine receptor mediated sustained post-exercise vasodilator responses compared to endurance trained young adults. METHODS: A randomized, double-blind placebo-controlled crossover study including 6 endurance trained (3F, 3M; ages 18-26) and 5 sedentary (3F, 2M; ages 22-29) adults was completed. Subjects consumed either combined histamine H1 and H2 receptor blockade with 540 mg fexofenadine (Allegra, H1 receptor blocker) and 300mg ranitidine (Zantac, H2 receptor blocker), or placebo pills containing only the inactive ingredients of fexofenadine and ranitidine. Pre-exercise vascular blood flow and conductance measurements were made every 30 minutes for 90 minutes. Post-exercise measurements were made every 30 minutes for 2 hours. Subjects completed 1 hour of dynamic knee extension exercise at 60% of maximal work rate. Subject demographics and baseline variables were analyzed using independent t-tests. Post-exercise differences between groups in the blockade and placebo conditions were analyzed using a mixed model ANOVA with repeated measures. All values are reported as mean ± SE. RESULTS: The endurance trained group had higher self-reported weekly physical activity compared to the sedentary group (73.03 ± 10.5 vs. 27.4 ± 9.5 METhr/wk, p=0.012). Pre-exercise mean arterial pressure was not different between the two groups in either placebo or blockade conditions (trained placebo: 83±2, trained blockade: 84±2, sedentary placebo: 84±1, sedentary blockade: 86±3 mmHg, p=0.745). Baseline femoral vascular conductance was not different between groups in either placebo or blockade condition (p=0.905). At 60 minutes post exercise, the change in femoral vascular conductance from baseline was not different between the groups for either placebo or blockade condition, although there was a trend towards drug effect of histamine receptor blockade (p=0.192). CONCLUSION: These preliminary results suggest that there is no difference in post-exercise femoral vascular conductance between endurance trained and sedentary young adults. Supported by NIH grant HL115027

STEADY STATE SKELETAL MUSCLE TEMPERATURE DURING MODERATE INTENSITY SINGLE LEG DYNAMIC KNEE EXTENSION EXERCISE

J.E. Mangum, M.J. Luttrell, M.C. Peck, M.R. Ely, D.C. Sieck, P. Abdala, J.R. Halliwill FACSM University of Oregon, Eugene OR In resting skeletal muscle, there is a temperature gradient with deeper tissue typically having higher temperatures than more superficial tissue. During exercise, skeletal muscle temperature increases with the rise in metabolism. Our lab has previously used a model of dynamic knee extension exercise which consists of single-leg kicking for 60 minutes at 60% of peak power output. The rate of skeletal muscle temperature rise, maximal temperature attained and range of intramuscular temperatures with this mode of exercise is unknown. PURPOSE: To examine the changes in skeletal muscle temperature at three different depths during exercise using this model. METHODS: Five young (ages 21-38) healthy male subjects completed the exercise protocol and intramuscular temperature was measured via an intramuscular thermocouple that measured temperature at three different depths within the vastus lateralis. Individual temperatures from each depth were measured and also averaged to express a mean intramuscular temperature. RESULTS: Within 10 minutes of exercise, mean intramuscular temperature increased from 34.59 ± 0.44°C to 37.06 ± 0.10°C (mean ± SE, p \u3c .01). By 30 minutes, mean intramuscular temperature reached a plateau of 39.15 ± 0.11°C, and remained there until the end of exercise. The variability of temperature in muscle, expressed as the range of the three different intramuscular temperatures, decreased from 1.40 ± 0.39°C to 0.60 ± 0.21°C by 30 minutes (p=.08), and did not further decrease to the end of exercise . CONCLUSIONS: These data suggest that skeletal muscle temperature increases rapidly during exercise, and the heterogeneity in temperatures typically associated with depth is reduced. As well, these data suggest that there is a steady intramuscular temperature reached within 30 minutes of steady state exercise at 60% of peak power output. Support provided by NIH grant HL115027

ANTIHISTAMINES SLOW ENDURANCE EXERCISE PERFORMANCE IN HIGHLY COMPETITIVE CYCLISTS

M.R. Ely1, D.C. Sieck1, J.E. Mangum1, E.A. Larson1, L.C. Brito2, C.T. Minson1FACSM, J.R. Halliwill1FACSM 1University of Oregon. Eugene, OR; 2University of Sao Paulo, Sao Paulo, Brazil Histamine, commonly associated with allergies and immune responses is released/produced within skeletal muscle during exercise. In humans, blocking histamine’s actions via antihistamines did not influence speed, power, or time to completion of short-duration, high-intensity exercise. Conversely, in rodents, antihistamines decreased the speed and duration components of endurance tasks. It is unknown if the differential exercise outcomes between humans and rodents from antihistamines is species specific or related to exercise intensity/duration. PURPOSE: To test the effects of antihistamines on cycling time trial performance preceded by rest or exercise. It was hypothesized that H1/H2antihistamines would slow the time to completion of a fixed-distance time-trial compared to placebo, and the effect would be greater following an endurance-exercise bout. METHODS: Eleven (3F) competitive cyclists (Cat 1-3) performed six 10km time-trials on separate days. The first two trials served as a familiarization and repeatability was assessed by calculating a coefficient of variation (CV). The next four 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; H1receptor blocker, and 300 mg of ranitidine; H2receptor blocker) or placebo 60 min prior to the start of rest/exercise. Two-Way RMANOVA, effect size (ES = Cohen’s dz), 95% CI, and CV from familiarization trials were used to determine the presence, strength, and meaningfulness of differences between the trials. RESULTS: A reduction in time to completion occurred 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). The day-to-day 10 km variability (CV) was 0.98%. The percent change in time-to-completion between placebo and antihistamine was likely trivial 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). CONCLUSION: Antihistamines slowed 10km time-trials in highly competitive cyclists. Support provided by: The Eugene & Clarissa Evonuk Memorial Graduate Fellowship & The ACSM Northwest Student Research Award