Examining the Effects of Oral Contraceptive Use on Thermoregulation

Purpose: The purpose of this investigation was to evaluate the effects of combined (estradiol and progestin) monophasic oral contraceptive pill (OCP) use on thermoregulation. Further, we sought to evaluate OCP use on acute rehydration post-exercise in the heat using recommended rehydration guidelines. Methods: Twelve healthy, aerobically trained (VO2peak = 47.8 ± 4.7 mL/kg/min), long term female oral contraceptive users completed a familiarization trial and two experimental days separated by ≥ 7 days. The two experimental trials were identical except for the hormone dosing phase. One trial was completed during the third week of active pill dosing (ACT) and one during the placebo week (PLA) of their normally prescribed OCPs. Participants completed 90 minutes of cycling in 30ºC and 55% relative humidity and a rehydration protocol. Exercise intensity was set at 55% of the wattage attained during the final stage of the VO2peak test. Trec, heart rate, blood pressure and perceptual measurements were recorded every 15-minutes. Body mass change was measured continuously and recorded every 15-minutes and subsequently used to provide water (warmed to 38°C) to replace sweat losses. Water was given to the participant to match 50% of sweat loss at each time point. Metabolic data (VO2) wattage and cadence was collected at 30-minutes, 60-minutes, 75-minutes and at the cessation of exercise (Hashimoto et al., 2016) to ensure work intensity was kept constant. 125% of fluid lost was replaced via a recovery beverage and water post-exercise. Results: Tre demonstrated a significant main effect difference for ACT to be greater than PLA compared to PLA (F1.55,15.53 = 74.019, P \u3c 0.001). There was also a significant main effect for Tre to increase over time, regardless of trial (F1,10 = 24.064, P \u3c 0.001). There was not an interaction of time x trial (F1.96,19.62 = 1.822, P = 0.189) for Tre. There was no difference in overall change in temperature (baseline to maximum temperature) between trials (ACT: 1.3 ± 0.5ºC, PLA: 1.4 ± 0.4ºC, t10 = -0.588, P = 0.570). Post-exercise, there was no difference between trials in the amount of fluid consumed (ACT: 1007 ± 256 mL; PLA: 921 ± 448 mL, t10 = 0.874, P = 0.403). There was no difference in spot sample USG assessed 3-h post-trial between trials (t7 = -0.743, P = 0.487). Likewise, 3-h spot sample urine osmolality was not different between trials (t7 = - 1.177, P = 0.287). Urgency to void at 3-h post-trial was not different between groups (t7 = - 1.000, P = 0.351). Perception of thirst was not different 3-h post-trial (t7 = - 0.3859, P = 0.711). Conclusion: We demonstrated a significant difference in core temperature elevation during the ACT trial. However, in following recommended hydration guidelines, OCP phase has no effect on fluid retention post-exercise in the heat

Sex, But Not Spontaneous Cardiovagal Baroreflex Sensitivity, Predicts Tolerance To Simulated Hemorrhage

Some, but not all studies, suggest that spontaneous cardiovagal baroreflex sensitivity (cBRS; i.e., autonomic control of heart rate) is lower in females. However, it is unknown whether cBRS values are associated with hemorrhagic tolerance, which has repeatedly been demonstrated to be lower in females. PURPOSE: Therefore, the purpose of this study was to test the hypothesis that resting spontaneous cBRS is lower in females and that cBRS is associated with differences in hemorrhagic tolerance between the sexes. METHODS: 25 females (age: 26 ± 6 years) and 27 males (age: 30 ± 5 years) completed a progressive lower-body negative pressure (LBNP – a simulation of hemorrhage) protocol starting at -40 mmHg, which was reduced by 10 mmHg every 3 minutes until presyncope. Presyncope was defined by the subject feeling faint and/or nauseous; a rapid decline in blood pressure (BP) \u3c systolic BP of 80 mmHg; and/or a relative bradycardia accompanied by narrowing of pulse pressure. LBNP tolerance was quantified as cumulative stress index (CSI; mmHg*min). Heart rate (HR) and beat-to-beat BP (finometer) were measured continuously. Spontaneous cBRS was analyzed using the sequence method (i.e., ≥ 3 consecutive cardiac cycles of concordant changes in R-R interval and systolic BP, r2 ≥ 0.8 for such sequences). Data were compared between sexes using a Mann-Whitney U test. A least squares multiple linear regression was used to compare the effect of sex and cBRS on CSI. Data are presented as median ± IQR. RESULTS: Resting BP and HR were not different between the sexes (p \u3e 0.36 for both). Resting cBRS was not different between females and males (21 ± 16 vs. 22 ± 11 ms/mmHg, respectively, p = 0.73). As expected, females had a lower tolerance to LBNP (Females: 385 ± 322, Males: 918 ± 418 mmHg*min, p \u3c 0.0001). Multiple linear regression analysis revealed a significant effect of sex (β = 408, p= 0.04), but not resting cBRS (β = 2.4, p = 0.69) or sex*cBRS (i.e., interaction; β = 1.32, p = 0.87), on CSI. When data from both sexes were combined, there was no correlation between resting cBRS and CSI (r = 0.05, p = 0.71). CONCLUSION: Our cohort did not exhibit sex-related differences in resting cBRS. As expected, females had a lower tolerance to simulated hemorrhage. Importantly, we demonstrated that resting cBRS does not explain the observed sex differences in hemorrhagic tolerance

Gastrointestinal Cell Injury and Percieved Symptoms after Running the Boston Marathon

Gastrointestinal (GI) disturbances are a prevalent cause of marathon related complaints, and in extreme cases can promote life-threatening conditions such as exertional heat stroke. PURPOSE: Our aim was to study intestinal cell injury (via intestinal fatty acid binding protein [I-FABP]) and perceived GI distress symptoms among marathon runners. Potential risk factors (e.g., inadequate sleep) that could exacerbate GI disturbances in healthy, trained endurance runners were also examined. METHODS: A parallel mixed-methods study design was utilized. 2019 Boston Marathon participants were recruited via email. Before the race subjects completed surveys describing demographics and training history. Immediately pre-race, post-race, and 24-hours post-race participants completed a GI questionnaire to assess presence and severity of symptoms, a survey regarding risk factors (e.g., recent illness, medications) that could promote GI disturbances, and provided a urine sample. Due to weather, blood samples were only collected immediately and 24-hours post-race. RESULTS: A total of 40 runners (males: n = 19, age = 44.9 ± 10.8 years; females: n = 21, age = 44.8 ± 10.6 years) completed this study. I-FABP significantly decreased from post-race (3367.5 ± 2633.5 pg/ml) to 24-hours post-race (1657.3 ± 950.7 pg/ml, t(39) = -4.228, p \u3c .001, d = -.669). A significant difference in overall GI symptom scores across the three time points occurred (F(2, 39) = 41.37, p \u3c .001). Compared to pre-race (.09 ± .12) and 24-hour post-race (.44 ± .28), the highest average score occurred post-race (.84 ± .68). Post-race I-FABP (r = .31, p = .048) and post-race urine specific gravity (r = .33, p = .041) were significantly correlated with post-race GI symptom scores. CONCLUSION: Our study further supports the individualized presentation of GI disturbances, with participants experiencing a wide range of risk factors that can influence the extent of GI damage and perceived symptoms during and after exercise

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Response to a Water Bolus in Long Term Oral Contraceptive Users

The purpose of our study was to determine the responses to an acute water bolus in long-term oral contraception (OCP) users. Seventeen female volunteers (27 ± 5 y, 64.1 ± 13.7 kg, 39.6 ± 5.9 kg/LBM) provided consent and enrolled in our study. All were long-term OCP users and participated in two trials, one during the active pill (High Hormone, HH) dose of their prescribed OCP and one during the sham pill (Low Hormone, LH) dose. Participants reported to the laboratory euhydrated, were fed breakfast, remained seated for 60 min and were provided a bolus of room temperature water in the amount of 12 mL/kg/LBM. Urine output over 180 min was measured. Nude body mass was measured pre- and post-trial. Urine specific gravity (USG) and urine osmolality were analyzed. Between trials, there were no differences in 3-h total urine volume (P = 0.296), 3-h USG (P = 0.225), 3-h urine osmolality (P = 0.088), or 3-h urine frequency (P = 0.367). Heart rate was not different between trials (P = 0.792) nor over time (P = 0.731). Mean arterial pressure was not different between trials (P = 0.099) nor over time (P = 0.262). Perceived thirst demonstrated a significant main effect for increasing over time regardless of trial (P \u3c 0.001) but there was no difference between trials (P = 0.731). The urgency to void was not different between trials (P = 0.149) nor over time (P = 0.615). Plasma volume change was not different between trials (P = 0.847) (HH: −3.4 ± 5.0, LH post: −3.8 ± 4.5%) and plasma osmolality did not differ between trials (P = 0.290) nor over time (P = 0.967) (HH pre: 290 ± 4, HH post: 289 ± 4, LH pre: 291 ± 4, LH post: 291 ± 4 mosm/L). Blood glucose significantly decreased over time (P \u3c 0.001) but there was no difference between trials (P = 0.780) (HH pre: 95.9 ± 113.9, HH post: 86.8 ± 6.5, LH pre: 95.9 ± 13.5, LH post: 84.6 ± 9.4 mmol/L). Copeptin concentration did not differ between phases of OCP use (P = 0.645) nor from pre- to post-trial (P = 0.787) Despite fluctuations in hormone concentrations, responses to a water bolus seem to be unaffected in OCP users in euhydrated, resting conditions

Sublingual Sufentanil Attenuates Perceived Pain, But Not Blood Pressure Responses, During A Cold Pressor Test

Sublingual sufentanil was developed to reduce pain following a traumatic injury in the field (e.g., battlefield). However, it is unknown whether an analgesic dose of sufentanil affects cardiovascular responses to a painful stimulus in humans. PURPOSE: We tested the hypothesis that sublingual sufentanil blunts pain perception and the accompanying cardiovascular responses during a cold pressor test (CPT). METHODS: Twenty-nine adults, 15 males and 14 females (age: 29 ± 5 years, body mass: 74 ± 8 kg, body mass index: 25 ± 2 kg/m2) participated in this double-blind, randomized, crossover, placebo-controlled trial. Following sublingual administration of sufentanil (30 µg) or placebo, participants underwent a two-minute resting baseline period and then a two-minute CPT (hand in 0.07 ± 0.10°C ice-water), while heart rate (electrocardiography) and beat-to-beat blood pressure (photoplethysmography - Finometer) were measured continuously. Pain perception (100 mm visual analog scale) was compared between trials via a two-tailed Wilcoxon Signed-Rank test. Heart rate and blood pressure responses were compared using a mixed effects model (trial x time). Changes (Δ) in heart rate and blood pressure from baseline to the last 30 seconds of the CPT were compared using a two-tailed Wilcoxon Signed-Rank test and a two-tailed paired t-test, respectively. RESULTS: Sufentanil attenuated perceived pain (sufentanil: 35 [27 – 53] vs. placebo: 68 [38 – 82] mm, p \u3c 0.001) during the CPT. The magnitude of the increase in heart rate to the CPT was influenced by the drug (trial: p = 0.061, time: p \u3c 0.001, interaction: p \u3c 0.001), with the Δ heart rate being greater for the placebo trial (p = 0.002). Both absolute mean blood pressure responses (trial: p = 0.071, time: p \u3c 0.001, interaction: p = 0.245) and Δ mean blood pressure to the CPT (sufentanil: 15 ± 9 vs. placebo: 16 ± 8, p = 0.334) were not different between trials. CONCLUSION: These data suggest that 30 µg of sublingual sufentanil attenuates perceived pain, but not the accompanying blood pressure responses, during the CPT

Sex Differences in Sympathetic Responses to Lower Body Negative Pressure

Introduction Trauma-induced hemorrhage is a leading cause of death in prehospital settings. Experimental data demonstrate that females have a lower tolerance to simulated hemorrhage (i.e., central hypovolemia). However, the mechanism(s) underpinning these responses are unknown. Therefore, this study aimed to compare autonomic cardiovascular responses during central hypovolemia between the sexes. We hypothesized that females would have a lower tolerance and smaller increase in muscle sympathetic nerve activity (MSNA) to simulated hemorrhage. Methods Data from 17 females and 19 males, aged 19-45 yr, were retrospectively analyzed. Participants completed a progressive lower-body negative pressure (LBNP) protocol to presyncope to simulate hemorrhagic tolerance with continuous measures of MSNA and beat-to-beat hemodynamic variables. We compared responses at baseline, at two LBNP stages (-40 and -50 mmHg), and at immediately before presyncope. In addition, we compared responses at relative percentages (33%, 66%, and 100%) of hemorrhagic tolerance, calculated via the cumulative stress index (i.e., the sum of the product of time and pressure at each LBNP stage). Results Females had lower tolerance to central hypovolemia (female: 561 ± 309 vs male: 894 ± 304 min·mmHg [time·LBNP]; P = 0.003). At LBNP -40 and -50 mmHg, females had lower diastolic blood pressures (main effect of sex: P = 0.010). For the relative LBNP analysis, females exhibited lower MSNA burst frequency (main effect of sex: P = 0.016) accompanied by a lower total vascular conductance (sex: P = 0.028; main effect of sex). Conclusions Females have a lower tolerance to central hypovolemia, which was accompanied by lower diastolic blood pressure at -40 and -50 mmHg LBNP. Notably, females had attenuated MSNA responses when assessed as relative LBNP tolerance time.</p

Age alters the thermoregulatory responses to extreme heat exposure with accompanying activities of daily living

Older adults are at greater risk for heat-related morbidity and mortality, due in part to age-related reductions in heat dissipating capabilities. Previous studies investigating the impact of age on responses to heat stress used approaches that lack activities of daily living and therefore may not accurately depict the thermal/physiological strain that would occur during actual heatwaves. We sought to compare the responses of young (18-39 yr) and older (≥65 yr) adults exposed to two extreme heat simulations. Healthy young (n = 20) and older (n = 20) participants underwent two 3-h extreme heat exposures on different days: 1) DRY (47°C and 15% humidity) and 2) HUMID (41°C and 40% humidity). To mimic heat generation comparable with activities of daily living, participants performed 5-min bouts of light physical activity dispersed throughout the heat exposure. Measurements included core and skin temperatures, heart rate, blood pressure, local and whole body sweat rate, forearm blood flow, and perceptual responses. Δ core temperature (Young: 0.68 ± 0.27°C vs. Older: 1.37 ± 0.42°C; P &lt; 0.001) and ending core temperature (Young: 37.81 ± 0.26°C vs. Older: 38.15 ± 0.43°C; P = 0.005) were greater in the older cohort during the DRY condition. Δ core temperature (Young: 0.58 ± 0.25°C vs. Older: 1.02 ± 0.32°C; P &lt; 0.001), but not ending core temperature (Young: 37.67 ± 0.34°C vs. Older: 37.83 ± 0.35°C; P = 0.151), was higher in the older cohort during the HUMID condition. We demonstrated that older adults have diminished thermoregulatory responses to heat stress with accompanying activities of daily living. These findings corroborate previous reports and confirm epidemiological data showing that older adults are at a greater risk for hyperthermia.NEW &amp; NOTEWORTHY Using an experimental model of extreme heat exposure that incorporates brief periods of light physical activity to simulate activities of daily living, the extent of thermal strain reported herein more accurately represents what would occur during actual heatwave conditions. Despite matching metabolic heat generation and environmental conditions, we show that older adults have augmented core temperature responses, likely due to age-related reductions in heat dissipating mechanisms.</p

Attrition of Well-Healed Burn Survivors to a 6-Month Community-Based Exercise Program:A Retrospective Evaluation

The purpose of this study was to evaluate whether burn survivors have lower adherence compared to non-burned control individuals during a 6-month community-based exercise program. In burn survivors, we sought to answer if there was a relation between the size of the burn injury and dropout frequency. Fifty-two burn survivors and 15 non-burned controls (n = 67) were recruited for a 6-month community-based (ie, non-supervised), progressive, exercise training program. During the exercise program, 27% (ie, 4 of the 15 enrolled) of the non-burned individuals dropped out of the study, while 37% (ie, 19 of the 52) of the burn survivors dropped out from the study. There was no difference in the percentage of individuals who dropped out between groups (P = .552). There was no difference in size of the burn injury, expressed as percent body surface area burned (%BSA) between the burn survivors that dropped out versus those who completed the exercise regimen (P = .951). We did not observe a relation between %BSA burned and dropouts (log odds = -0.15-0.01(%BSA), B = -0.01, SE = 0.015, P = .541). There was no effect of %BSA burned on the probability of dropout [Exp (B) = 0.991, 95% CI (0.961, 1.020)] and there were no differences in the percentage of individuals who dropped out of the study based on %BSA burned (χ2(1) = 0.44, P = .51). These data demonstrate that burn survivors have similar exercise adherence relative to a non-burned group and the extent of a burn injury does not affect exercise program adherence.</p