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

Predictors of Performance during a 161 km Mountain Footrace

Training volume and cardiovascular dynamics influence endurance performance. However, there is limited information on the interplay between training volume, cardiovascular dynamics, and performance in ultra-marathon athletes. PURPOSE: We aimed to determine predictors of performance in finishers of the 2023 Western States Endurance Run (WSER). METHODS: Sixty participants who finished the race (49 males/11 females; mean age: 44.7 ± 9.6 y, range: 26–66 y; BMI: 22.7 ± 2.2 kg/m2) completed pre-race surveys including average training volume (AV) and peak training volume (PV), as well as resting cardiovascular measures including resting heart rate (RHR) and augmentation index (AIx), a measure of wave reflection characteristics. Based on WSER completion time, we calculated average running velocity (RV). We assessed associations among 22 variables using bivariate correlation analysis (Pearson’s Correlation for normally distributed data and Spearman’s Rank Correlation if normality was not met). Within our listed variables, normality was met in age and AV. Additionally, we completed multiple regression analyses for predictors. We present descriptive data as mean ± SD. RESULTS: Participants had an average RV of 6.33 ± 0.97 km/h (3.93 ± 0.6 mph), and reported an AV of 91.9 ± 24.5 km/wk (57.1 ± 15.2 miles/wk) and a PV of 141.0 ± 47.2 km/wk (87.6 ± 29.3 miles/wk). We observed significant associations between RV and age (r(58) = -0.57, p r(58) = 0.41, p r(58) = 0.34, p R2 = 0.37; F(3,56) = 12.4, pb1 = 0.013; t(56) = 2.57, p = 0.013), resulting in a 0.33 km/h increase in RV for every 25-km increase in AV. Last, significant relations existed between RV and AIx (r(58) = -0.30, p = 0.022); and RHR (r(58) = -0.26, p = 0.046). CONCLUSION: We found that (1) average weekly training volume is a significant predictor of performance in elite ultra-marathon athletes and (2) race performance was inversely associated with resting arterial wave reflection characteristics and heart rate

The effect of mild hypohydration on resting and reflex blood pressure regulation in healthy young and old adults

Farquhar, William B.Arterial blood pressure (BP) dysregulation is associated with increased future risk of cardiovascular disease, the leading cause of death among adults in the United States. Indices of BP dysregulation include 1) high resting BP (i.e., hypertension), 2) high BP variability, and 3) exaggerated BP responses during exercise. Hypohydration is common among adults in daily life, is associated with future cardiovascular disease risk, and has greater incidence during aging. However, it is unknown whether hypohydration is a causative factor for BP dysregulation. Therefore, we sought to determine if acute hypohydration causes BP dysregulation. In randomized crossover fashion, 45 non-obese and non-hypertensive adults (35 young & 10 old adults with similar body mass index values and habitual physical activity levels) completed: 1) a normally hydrated control condition (CON) via a three-day protocol with prescribed water intake, and 2) a water deprivation condition (WD) via a stepwise reduction in water intake over three-days concluded with a 16-hour water abstention period. All experimental visits were separated by at least one week. No participants were currently taking any anti-hypertensive medications (inclusive of diuretics). Participants collected their urine and underwent ambulatory BP measurements throughout the 24-hour period preceding each experimental visit. On the day of the experimental visit we measured hydration biomarkers and brachial BP (automated oscillometric device). While participants lie quietly in the supine position, we continuously assessed heart rate (single-lead ECG), beat-to-beat BP (photoplethysmography), muscle sympathetic nerve activity (peroneal microneurography; 23 paired recordings), and common femoral artery blood flow (sonography) at rest and two minutes of isometric handgrip exercise. WD elicited mild hypohydration as evidenced by elevated plasma osmolality, urine osmolality and specific gravity, and thirst rating similarly among young and old adults. Despite mild hypohydration, WD did not increase: 1) resting or ambulatory daytime BP values, 2) resting or ambulatory BP variability, or 3) sympathetic or BP responses during handgrip exercise or the cold pressor test in either young or old adults. Together, our findings suggest that this model of acute mild hypohydration does not alter resting or reflex BP regulation in healthy young and old adults.University of Delaware, Department of Kinesiology and Applied PhysiologyPh.D

Evidence for Chronotropic Incompetence in Well-healed Burn Survivors

Due to various pathophysiological responses associated with a severe burn injury, we hypothesized that burn survivors exhibit chronotropic incompetence. To test this hypothesis, a graded peak oxygen consumption (V̇O2peak) test was performed in 94 adults (34 nonburned, 31 burn survivors with 14-35% body surface area grafted, and 29 burn survivors with &gt;35% body surface area grafted). The threshold of 35% body surface area grafted was determined by receiver operating characteristic (ROC) curve analysis. Peak exercise heart rates (HRmax) were compared against age-predicted HRmax within each group. The proportion of individuals not meeting their age-predicted HRmax (within 5 b/min) were compared between groups. Age-predicted HRmax was not different from measured HRmax in the nonburned and moderate burn groups (P = .09 and .22, respectively). However, measured HRmax was 10 ± 6 b/min lower than the age-predicted HRmax in those with a large burn injury (P &lt; .001). While 56 and 65% of individuals in the nonburned and moderate burn group achieved a measured HRmax within 5 b/min or greater of age-predicted HRmax, only 21% of those in the large burn group met this criterion (P &lt; .001). These data provide preliminary evidence of chronotropic incompetence in individuals with severe burn injury covering &gt;35% body surface area.</p

THE EFFECT OF FEMALE AGING ON SYMPATHETIC TRANSDUCTION DURING THE COLD PRESSOR TEST

BACKGROUND: Older female adults (OF) have the highest risk for hypertension and cardiovascular disease among any demographic in America. Exaggerated blood pressure (BP) responses during the cold pressor test (CPT) are associated with higher cardiovascular disease risk. However, previous studies report no age-related differences in BP or sympathetic responses during the CPT in females, but data are limited and partly confounded by differences in body mass index (BMI), which can independently influence CPT responses. Therefore, we tested the hypothesis that aging increases BP and sympathetic responses during the CPT in OF (\u3e55 years) compared with YF (18 - 35 years) matched for BMI. METHODS: We studied nine post-menopausal OF and 17 YF (early follicular phase) with brachial BP \u3c140/90 mmHg and BMI \u3c30 kg/m2. We measured mean BP (photoplethysmography) during a 10-min rest period and a 2-min CPT. In a subset (6 OF, 10 YF), we also measured muscle sympathetic nerve activity (MSNA; microneurography). We calculated time-averaged sympathetic transduction of BP during the CPT (CPT-baseline) as sympathetic-pressure ratios (mean BP/MSNA burst frequency & mean BP/MSNA total activity). We compared age groups using unpaired, two-tailed t-tests for normally distributed data and Mann-Whitney U tests for non-normally distributed data (i.e., failed Shapiro-Wilk test). RESULTS: The data are presented as OF vs. YF with mean±SD or median[IQR]. By design, age (66±6 vs. 24±4 years, p\u3c0.0001), but not BMI (22.8±2.8 vs. 22.6±3.5 kg/m2, p=0.85), was higher in OF. Mean BP (97±13 vs. 78±4 mmHg, p\u3c0.0001), MSNA burst frequency (35±6 vs. 11±6 bursts/min, p\u3c0.0001), and MSNA total activity (1096[559] vs. 114[147] AU, p=0.001) were higher in OF at rest. Mean BP responses during the CPT did not differ between groups (∆17±9 vs. 14±8 mmHg, p=0.79). However, MSNA burst frequency (∆7±5 vs. 17±11 bursts/min, p=0.01) and total activity (∆24[93] vs. 514[3648] %, p\u3c0.001) responses during the CPT were higher in YF. Finally, the sympathetic-pressure ratios did not differ between groups (1.6[13.7] vs. 0.7[0.4] mmHg/bursts/min, p=0.09 & 0.25[1.69] vs. 0.02[0.04] mmHg/%, p=0.40). CONCLUSION: In partial support of our hypothesis, these preliminary data suggest that MSNA, but not BP, responses during the CPT are attenuated in OF. A higher baseline MSNA in OF relative to YF may explain these reduced sympathetic responses during the CPT

THE EFFECT OF FEMALE AGING ON BLOOD PRESSURE AND SYMPATHETIC REACTIVITY DURING END-EXPIRATORY APNEA

BACKGROUND: Older females (OF) have greater cardiovascular risk and blood pressure (BP) reactivity compared to younger females (YF). In cohorts of males and females, aging augments BP reactivity and reduces sympathetic reactivity to chemoreflex stimulation. However, there is limited data on how aging affects BP reactivity to chemoreflex stimulation in females. Therefore, we tested the hypothesis that OF vs. YF would exhibit greater BP reactivity and a lower sympathetic reactivity during an end-expiratory breath-hold (EEBH; chemoreflex stimulus). METHODS: We measured beat-to-beat BP and Modelflow-derived hemodynamics (photoplethysmography; 13 YF, 8 OF) during a two-minute rest and maximal voluntary duration EEBH. In a subset, we also measured muscle sympathetic nerve activity (MSNA via microneurography; 9 YF, 5 OF). We tested YF during the early follicular phase and OF were post-menopausal. We compared variables at rest and in response to the EEBH between groups using unpaired, two-tailed t-tests for normally distributed data and Mann-Whitney U tests for non-normally distributed data. All data are presented as OF vs. YF with mean±SD or median[IQR]. RESULTS: Age (OF 66±6 vs. YF 23±2 years, p\u3c0.001), but not BMI (OF 21.8[3.7] vs. YF 22.6[3.6] kg/m2, p=0.491), was different between groups. OF had a longer EEBH duration (OF 46[28] vs. YF 29[9] s, p\u3c0.001). At rest, mean BP (OF 99±13 vs. YF 81±4 mmHg, p\u3c0.001), MSNA burst frequency (OF 32±9 vs. YF 9±7 bursts/min, p\u3c0.001), and MSNA total activity (OF 802±296 vs. YF 90±121 AU, p\u3c0.001) were higher in OF. The change in MAP (OF 27[10] vs. YF 15[13] mmHg, p=0.045) was larger in OF whereas the relative change in MSNA total activity (OF 369±182 vs. YF 1014±620 %, p=0.014) was smaller in OF during the EEBH. However, the increases in MSNA burst frequency (OF 15±7 vs. YF 16±9 bursts/min, p=0.833) during the EEBH were not different between groups. Additionally, the change in cardiac output was lower in OF (OF -0.3±0.5 vs. YF 0.2±0.3 L/min, p=0.005) but the change in systemic vascular resistance was greater in OF (OF 9.4±2.8 vs. YF 3.2±1.9 mmHg/L/min, p\u3c0.001). CONCLUSION: The smaller relative increases in MSNA total activity during EEBH in OF suggest reduced chemoreflex sensitivity in female aging. Interestingly, these preliminary data suggest that augmented BP reactivity in OF was driven by vascular resistance despite smaller increases in MSNA during EEBH

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

A High Salt Meal Does Not Augment Blood Pressure Responses During Maximal Exercise

Augmented blood pressure (BP) responses during exercise are predictive of future cardiovascular disease. High dietary sodium (Na+) increases BP responses during static exercise. It remains unclear if high dietary Na+ augments BP responses during dynamic exercise. The purpose of this study was to test the hypothesis that an acute high-Na+ meal would augment BP responses during dynamic exercise. Twenty adults (10 male/10 female; age, 26 ± 5 years; BP, 105 ± 10/57 ± 6 mm Hg) were given a high-Na+ meal (HSM; 1495 mg Na+) and a low-Na+ meal (LSM; 138 mg Na+) separated by at least 1 week, in random order. Serum Na+ and plasma osmolality were measured. Eighty minutes following the meal, participants completed a graded-maximal exercise protocol on a cycle ergometer. Heart rate, beat-by-beat BP, cardiac output, total peripheral resistance, and manual BP were measured at rest and during exercise. Both serum Na+ (HSM: Δ1.6 ± 2.0 vs LSM: Δ1.1 ± 1.8 mmol/L, P = 0.0002) and plasma osmolality (HSM: Δ3.0 ± 4.5 vs LSM: Δ2.0 ± 4.2 mOsm/(kg·H2O), P = 0.01) were higher following the HSM. However, the HSM did not augment BP during peak exercise (systolic BP: HSM: 170 ± 23 vs LSM: 171 ± 21 mm Hg, P = 0.81). These findings suggest that an acute high-salt meal does not augment BP responses during dynamic exercise in adults. Novelty The high-salt meal increased serum sodium and plasma osmolality compared with the low-salt meal. The high-salt meal did not augment blood pressure responses during maximal dynamic exercise. This is important as augmented blood pressure responses during exercise put individuals at greater risk for development of cardiovascular disease.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author