Kidney Function Biomarkers During Extreme Heat Exposure in Young and Older Adults.

This study investigates the effects of extreme heat exposure on kidney function using plasma-based biomarkers in young and older adults.

Advanced Cardiovascular Physiology in an Individual with Type 1 Diabetes After 10-Year Ketogenic Diet.

Adults with type 1 diabetes (T1D) have an elevated risk for cardiovascular disease (CVD) compared with the general population. HbA1c is the primary modifiable risk factor for CVD in T1D. Fewer than 1% of patients achieve euglycemia (<5.7%HbA1c). Ketogenic diets (KD; ≤50g carbohydrate/day) may improve glycemia and downstream vascular dysfunction in T1D by reducing HbA1c and insulin load. However, there are concerns regarding the long-term CVD risk from a KD. Therefore, we compared data collected in a 60-day window in an adult with T1D on exogenous insulin who consumed a KD for 10 years versus normative values in those with T1D (T1D norms). The participant achieved euglycemia with an HbA1c of 5.5%, mean glucose of 98[5]mg/dL(median[IQR]), and 90[11]%time-in-range 70-180mg/dL (T1D norms: 1st percentile for all); and low insulin requirements of 0.38±0.03IU/kg/day (T1D norms: 8th percentile). Seated systolic blood pressure (SBP) was 113mmHg (T1D norms: 18th percentile) while ambulatory awake SBP was 132±15mmHg (T1D target: <130mmHg), blood triglycerides were 69mg/dL (T1D norms: 34th percentile), low-density lipoprotein was 129mg/dL (T1D norms: 60th percentile), heart rate was 56bpm (T1D norms: >1SD below the mean), carotid-femoral pulse wave velocity was 7.17m/s (T1D norms: lowest quartile of risk), flow-mediated dilation was 12.8% (T1D norms: >1SD above mean), and cardiac vagal baroreflex gain was 23.5ms/mmHg (T1D norms: >1SD above mean). Finally, there was no indication of left ventricular diastolic dysfunction from echocardiography. Overall, these data demonstrate below-average CVD risk relative to T1D norms despite concerns regarding the long-term impact of a KD on CVD risk.

Faster Club Hockey Athletes Have Reduced Upper Leg Muscular Co-contraction During Maximal-Speed Sprinting.

Background: Most electromyographic (EMG) data for muscular activation patterns during ambulation is limited to older adults with existing chronic disease(s) walking at slow velocities. However, we know much less about the lower extremity muscle co-contraction patterns during sprinting and its relation to running velocity (i.e., performance). Therefore, we compared lower extremity muscular activation patterns during sprinting between slower and faster collegiate club hockey athletes. We hypothesized that faster athletes would have lower EMG-assessed co-contraction index (CCI) values in the lower extremities during over-ground sprinting. Results: Twenty-two males (age = 21[1] yrs (median[IQR]); body mass = 77.1 ± 8.6 kg (mean ± SD)) completed two 20-m over-ground sprints with concomitant EMG and asynchronous force plate testing. We split participants using median running velocity (FAST: 8.5 ± 0.3 vs. SLOW: 7.7 ± 0.3. Conclusions: m/s, p < 0.001). Faster athletes had lower CCI between the rectus femoris and biceps femoris (group: p = 0.05), particularly during the late swing phase of the gait cycle (post hoc p = 0.02). In agreement with our hypothesis, we found lower CCI values in the upper leg musculature during maximal-speed over-ground sprinting. These data from collegiate club hockey athletes corroborate other reports in clinical populations that the coordination between the rectus femoris and biceps femoris is associated with linear over-ground sprinting velocity.

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.

Burn size and environmental conditions modify thermoregulatory responses to exercise in burn survivors.

This project tested the hypothesis that burn survivors can perform mild/moderate-intensity exercise in temperate and hot environments without excessive elevations in core body temperature. Burn survivors with low (23 ± 5%TBSA; N = 11), moderate (40 ± 5%TBSA; N = 9), and high (60 ± 8%TBSA; N = 9) burn injuries performed 60 minutes of cycle ergometry exercise (72 ± 15 watts) in a 25°C and 23% relative humidity environment (ie, temperate) and in a 40°C and 21% relative humidity environment (ie, hot). Absolute gastrointestinal temperatures (TGI) and changes in TGI (ΔTGI) were obtained. Participants with an absolute TGI of >38.5°C and/or a ΔTGI of >1.5°C were categorized as being at risk for hyperthermia. For the temperate environment, exercise increased ΔTGI in all groups (low: 0.72 ± 0.21°C, moderate: 0.42 ± 0.22°C, and high: 0.77 ± 0.25°C; all P < .01 from pre-exercise baselines), resulting in similar absolute end-exercise TGI values (P = .19). Importantly, no participant was categorized as being at risk for hyperthermia, based upon the aforementioned criteria. For the hot environment, ΔTGI at the end of the exercise bout was greater for the high group when compared to the low group (P = .049). Notably, 33% of the moderate cohort and 56% of the high cohort reached or exceeded a core temperature of 38.5°C, while none in the low cohort exceeded this threshold. These data suggest that individuals with a substantial %TBSA burned can perform mild/moderate intensity exercise for 60 minutes in temperate environmental conditions without risk of excessive elevations in TGI. Conversely, the risk of excessive elevations in TGI during mild/moderate intensity exercise in a hot environment increases with the %TBSA burned.

Acute nasal breathing lowers diastolic blood pressure and increases parasympathetic contributions to heart rate variability in young adults.

There is growing interest in how breathing pace, pattern, and training (e.g., device-guided or -resisted breathing) affect cardiovascular health. It is unknown whether the route of breathing (nasal vs. oral) affects prognostic cardiovascular variables. Because nasal breathing can improve other physiological variables (e.g., airway dilation), we hypothesized that nasal compared with oral breathing would acutely lower blood pressure (BP) and improve heart rate variability (HRV) metrics. We tested 20 adults in this study [13 females/7 males; age: 18(1) years, median (IQR); body mass index: 23 ± 2 kg·m-2, means ± SD]. We compared variables between nasal- and oral-only breathing (random order, five min each) using paired, two-tailed t tests or Wilcoxon signed-rank paired tests with significance set to P < 0.05. We report the median (interquartile range) for diastolic BP and means ± SD for all other variables. We found that nasal breathing was associated with a lower mean BP (nasal: 84 ± 7 vs. oral: 86 ± 5 mmHg, P = 0.006, Cohen's d = 0.70) and diastolic BP [nasal: 68(8) vs. oral: 72(5) mmHg, P < 0.001, Rank-biserial correlation = 0.89] but not systolic BP (nasal: 116 ± 11 vs. oral: 117 ± 9 mmHg, P = 0.48, Cohen's d = 0.16) or heart rate (HR; nasal: 74 ± 10 vs. oral: 75 ± 8 beats·min-1, P = 0.90, Cohen's d = 0.03). We also found that nasal breathing was associated with a higher high-frequency (HF) contribution to HRV (nasal: 59 ± 19 vs. oral: 52 ± 21%, P = 0.04, Cohen's d = 0.50) and a lower low frequency-to-HF ratio at rest (nasal: 0.9 ± 0.8 vs. oral: 1.2 ± 0.9, P = 0.04, Cohen's d = 0.49). These data suggest that nasal compared with oral breathing acutely 1) lowers mean and diastolic BP, 2) does not affect systolic BP or heart rate, and 3) increases parasympathetic contributions to HRV.NEW & NOTEWORTHY There is growing interest in how breathing pace, pattern, and training (e.g., device-guided or -resisted breathing) affect prognostic cardiovascular variables. However, the potential effects of the breathing route on prognostic cardiovascular variables are unclear. These data suggest that nasal compared with oral breathing 1) lowers mean and diastolic blood pressure (BP), 2) does not affect systolic BP or heart rate (HR), and 3) increases parasympathetic contributions to heart rate variability (HRV). These data suggest that acute nasal breathing improves several prognostic cardiovascular variables.

Adjusting for muscle strength and body size attenuates sex differences in the exercise pressor reflex in young adults.

Females typically exhibit lower blood pressure (BP) during exercise than males. However, recent findings indicate that adjusting for maximal strength attenuates sex differences in BP during isometric handgrip (HG) exercise and postexercise ischemia (PEI; metaboreflex isolation). In addition, body size is associated with HG strength but its contribution to sex differences in exercising BP is less appreciated. Therefore, the purpose of this study was to determine whether adjusting for strength and body size would attenuate sex differences in BP during HG and PEI. We obtained beat-to-beat BP in 110 participants (36 females, 74 males) who completed 2 min of isometric HG exercise at 40% of their maximal voluntary contraction followed by 3 min of PEI. In a subset (11 females, 17 males), we collected muscle sympathetic nerve activity (MSNA). Statistical analyses included independent t tests and mixed models (sex × time) with covariate adjustment for 40% HG force, height2, and body surface area. Females exhibited a lower absolute 40% HG force than male participants (Ps < 0.001). Females exhibited lower Δsystolic, Δdiastolic, and Δmean BPs during HG and PEI than males (e.g., PEI, Δsystolic BP, 15 ± 11 vs. 23 ± 14 mmHg; P = 0.004). After covariate adjustment, sex differences in BP responses were attenuated. There were no sex differences in MSNA. In a smaller strength-matched cohort, there was no sex × time interactions for BP responses (e.g., PEI systolic BP, P = 0.539; diastolic BP, P = 0.758). Our data indicate that sex differences in exercising BP responses are attenuated after adjusting for muscle strength and body size.NEW & NOTEWORTHY When compared with young males, females typically exhibit lower blood pressure (BP) during exercise. Adjusting for maximal strength attenuates sex differences in BP during isometric handgrip (HG) exercise and postexercise ischemia (PEI), but the contribution of body size is unknown. Novel findings include adjustments for muscle strength and body size attenuate sex differences in BP reactivity during exercise and PEI, and sex differences in body size contribute to HG strength differences.

Cross-sectional analysis of racial differences in hydration and neighborhood deprivation in young adults.

BACKGROUND: Inadequate hydration is associated with cardiovascular and kidney disease morbidity and all-cause mortality. Compared with White individuals, Black individuals exhibit a higher prevalence of inadequate hydration, which may contribute to racial health disparities. However, the underlying reasons for these differences in hydration remain unclear. OBJECTIVE: This cross-sectional study aimed to investigate whether neighborhood deprivation contributes to racial differences in hydration status. METHODS: We assessed 24 Black and 30 White college students, measuring 24-hour urine osmolality, urine flow rate, urine specific gravity, and plasma copeptin concentration. Participants recorded their food and fluid intake for 3 d to assess total water intake from food and beverages. Neighborhood socioeconomic deprivation was measured using a tract-level Area Deprivation Index. RESULTS: Black participants exhibited higher urine osmolality (640 [314] compared with 440 [283] mOsm/kg H2O, respectively, P = 0.006) and lower urine flow rate (1.06 [0.65] compared with 1.71 [0.89] ml/min, respectively, P = 0.009) compared with White participants, indicating greater hypohydration among Black participants. Black participants reported lower total water intake from food and beverages than White participants (2.3 ± 0.7 compared with 3.5 ± 1.1 L/day, respectively, P < 0.01). Black participants exhibited higher copeptin than White participants (6.3 [3.1] compared with 4.5 [2.3] pmol/L, P = 0.046), and urine osmolality mediated 67% of the difference (P = 0.027). Black participants reported greater cumulative exposure to neighborhood deprivation during childhood (ages 0-18 y). Furthermore, neighborhood deprivation during childhood was associated with urine specific gravity (P = 0.031) and total water intake from food and beverages (P = 0.042) but did not mediate the racial differences in these measures. CONCLUSION: Our data suggest that compared with White young adults, Black young adults are hypohydrated and exhibit higher plasma copeptin concentration, and that greater neighborhood deprivation is associated with chronic underhydration irrespective of race. This trial was registered at clinicaltrials.gov as NCT04576338.

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 < 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 < 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 & 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.

The damaging duo: Obesity and excess dietary salt contribute to hypertension and cardiovascular disease.

Hypertension is a primary risk factor for cardiovascular disease. Cardiovascular disease is the leading cause of death among adults worldwide. In this review, we focus on two of the most critical public health challenges that contribute to hypertension-obesity and excess dietary sodium from salt (i.e., sodium chloride). While the independent effects of these factors have been studied extensively, the interplay of obesity and excess salt overconsumption is not well understood. Here, we discuss both the independent and combined effects of excess obesity and dietary salt given their contributions to vascular dysfunction, autonomic cardiovascular dysregulation, kidney dysfunction, and insulin resistance. We discuss the role of ultra-processed foods-accounting for nearly 60% of energy intake in America-as a major contributor to both obesity and salt overconsumption. We highlight the influence of obesity on elevated blood pressure in the presence of a high-salt diet (i.e., salt sensitivity). Throughout the review, we highlight critical gaps in knowledge that should be filled to inform us of the prevention, management, treatment, and mitigation strategies for addressing these public health challenges.

Acute beetroot juice reduces blood pressure in young Black and White males but not females.

A complex interplay of social, lifestyle, and physiological factors contribute to Black Americans having the highest blood pressure (BP) in America. One potential contributor to Black adult's higher BP may be reduced nitric oxide (NO) bioavailability. Therefore, we sought to determine whether augmenting NO bioavailability with acute beetroot juice (BRJ) supplementation would reduce resting BP and cardiovascular reactivity in Black and White adults, but to a greater extent in Black adults. A total of 18 Black and 20 White (∼equal split by biological sex) young adults completed this randomized, placebo-controlled (nitrate (NO3-)-depleted BRJ), crossover design study. We measured heart rate, brachial and central BP, and arterial stiffness (via pulse wave velocity) at rest, during handgrip exercise, and during post-exercise circulatory occlusion. Compared with White adults, Black adults exhibited higher pre-supplementation resting brachial and central BP (Ps ≤0.035; e.g., brachial systolic BP: 116(11) vs. 121(7) mmHg, P = 0.023). Compared with placebo, BRJ (∼12.8 mmol NO3-) reduced resting brachial systolic BP similarly in Black (Δ-4±10 mmHg) and White (Δ-4±7 mmHg) adults (P = 0.029). However, BRJ supplementation reduced BP in males (Ps ≤ 0.020) but not females (Ps ≥ 0.299). Irrespective of race or sex, increases in plasma NO3- were associated with reduced brachial systolic BP (ρ = -0.237, P = 0.042). No other treatment effects were observed for BP or arterial stiffness at rest or during physical stress (i.e., reactivity); Ps ≥ 0.075. Despite young Black adults having higher resting BP, acute BRJ supplementation reduced systolic BP in young Black and White adults by a similar magnitude, an effect that was driven by males.

Short-term high-salt consumption does not influence resting or exercising heart rate variability but increases MCP-1 concentration in healthy young adults.

High salt consumption increases blood pressure (BP) and cardiovascular disease risk by altering autonomic function and increasing inflammation. However, it is unclear whether salt manipulation alters resting and exercising heart rate variability (HRV), a noninvasive measure of autonomic function, in healthy young adults. The purpose of this investigation was to determine whether short-term high-salt intake 1) alters HRV at rest, during exercise, or exercise recovery and 2) increases the circulating concentration of the inflammatory biomarker monocyte chemoattractant protein 1 (MCP-1). With the use of a randomized, placebo-controlled, crossover study, 20 participants (8 females; 24 ± 4 yr old, 110 ± 10/64 ± 8 mmHg) consumed salt (3,900 mg sodium) or placebo capsules for 10 days each separated by ≥2 wk. We assessed HRV during 10 min of baseline rest, 50 min of cycling (60% V̇o2peak), and recovery. We quantified HRV using the standard deviation of normal-to-normal RR intervals, the root mean square of successive differences (RMSSD), and additional time and frequency domain metrics of HRV. Plasma samples were collected to assess MCP-1 concentration. No main effect of high salt or condition × time interaction was observed for HRV metrics. However, acute exercise reduced HRV (e.g., RMSSD time: P < 0.001, condition: P = 0.877, interaction: P = 0.422). High salt elevated plasma MCP-1 (72.4 ± 12.5 vs. 78.14 ± 14.7 pg/mL; P = 0.010). Irrespective of condition, MCP-1 was moderately associated (P values < 0.05) with systolic (r = 0.32) and mean BP (r = 0.33). Short-term high-salt consumption does not affect HRV; however, it increases circulating MCP-1, which may influence BP in young adults.

Inhibiting regional sweat evaporation modifies the ventilatory response to exercise: interactions between core and skin temperature.

In humans, elevated body temperatures can markedly increase the ventilatory response to exercise. However, the impact of changing the effective body surface area (BSA) for sweat evaporation (BSAeff) on such responses is unclear. Ten healthy adults (9 males, 1 female) performed eight exercise trials cycling at 6 W/kg of metabolic heat production for 60 min. Four conditions were used where BSAeff corresponded to 100%, 80%, 60%, and 40% of BSA using vapor-impermeable material. Four trials (one at each BSAeff) were performed at 25°C air temperature, and four trials (one at each BSAeff) at 40°C air temperature, each with 20% humidity. The slope of the relation between minute ventilation and carbon dioxide elimination (V̇E/V̇co2 slope) assessed the ventilatory response. At 25°C, the V̇E/V̇co2 slope was elevated by 1.9 and 2.6 units when decreasing BSAeff from 100 to 80 and to 40% (P = 0.033 and 0.004, respectively). At 40°C, V̇E/V̇co2 slope was elevated by 3.3 and 4.7 units, when decreasing BSAeff from 100 to 60 and to 40% (P = 0.016 and P < 0.001, respectively). Linear regression analyses using group average data from each condition demonstrated that end-exercise mean body temperature (integration of core and mean skin temperature) was better associated with the end-exercise ventilatory response, compared with core temperature alone. Overall, we show that impeding regional sweat evaporation increases the ventilatory response to exercise in temperate and hot environmental conditions, and the effect is mediated primarily by increases in mean body temperature.NEW & NOTEWORTHY Exercise in the heat increases the slope of the relation between minute ventilation and carbon dioxide elimination (V̇E/V̇co2 slope) in young healthy adults. An indispensable role for skin temperature in modulating the ventilatory response to exercise is noted, contradicting common belief that internal/core temperature acts independently as a controller of ventilation during hyperthermia.

Six Months of Exercise Training Improves Ventilatory Responses during Exercise in Adults with Well-Healed Burn Injuries.

INTRODUCTION: Pulmonary function is lower after a severe burn injury, which could influence ventilatory responses during exercise. It is unclear whether exercise training improves pulmonary function or ventilatory responses during exercise in adults with well-healed burn injuries. Therefore, we tested the hypothesis that exercise training improves pulmonary function and ventilatory responses during exercise in adults with well-healed burn injuries. METHODS: Thirty-nine adults (28 with well-healed burn injuries and 11 non-burn-injured controls) completed 6 months of unsupervised, progressive exercise training including endurance, resistance, and high-intensity interval components. Before and after exercise training, we performed comprehensive pulmonary function testing and measured ventilatory responses during cycling exercise. We compared variables using two-way ANOVA (group-time; i.e., preexercise/postexercise training (repeated factor)). RESULTS: Exercise training did not increase percent predicted spirometry, lung diffusing capacity, or airway resistance measures (time: P ≥ 0.14 for all variables). However, exercise training reduced minute ventilation ( V̇E ; time: P ≤ 0.05 for 50 and 75 W) and the ventilatory equivalent for oxygen ( V̇E /V̇O 2 ; time: P < 0.001 for 75 W) during fixed-load exercise for both groups. The ventilatory equivalent for carbon dioxide ( V̇E /V̇CO 2 ) during exercise at 75 W was reduced after exercise training (time: P = 0.04). The percentage of age-predicted maximum heart rate at the ventilatory threshold was lower in adults with well-healed burn injuries before ( P = 0.002), but not after ( P = 0.22), exercise training. Lastly, exercise training increased V̇E and reduced V̇E /V̇O 2 during maximal exercise (time: P = 0.005 for both variables). CONCLUSIONS: These novel findings demonstrate that exercise training can improve ventilatory responses during exercise in adults with well-healed burn injuries.

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 >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 < .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 < .001). These data provide preliminary evidence of chronotropic incompetence in individuals with severe burn injury covering >35% body surface area.

Habituation attenuates the sex-specific associations between ischemic pain, blood pressure, and arterial stiffness in young adults.

Cardiovascular reactivity (CVR) during physical stress is prognostic for incident cardiovascular disease. CVR is influenced by perceived pain. However, there is limited data on the effect of sex differences and repeated exposures to painful stimuli on CVR. We measured blood pressure (BP) and carotid-femoral pulse wave velocity (cf-PWV; an index of arterial stiffness) at rest, during isometric handgrip (HG) exercise at 30% of maximum voluntary contraction, and during postexercise circulatory occlusion (PECO) during two identical trials in 39 adults (20M/19F; 18-39 yr). We assessed participants' perceived pain using a visual analog scale after the first minute of each stimulus. We collected BP during minute 2 of each stimulus and cf-PWV during minute 3 of each stimulus. In male participants, we observed moderate associations (Ps ≤ 0.023) between perceived pain and changes in brachial diastolic (ρ = 0.620) and mean BP (ρ = 0.597); central diastolic, mean, and systolic BP (ρs = 0.519-0.654); and cf-PWV (ρ = 0.680) during PECO in trial 1, but not trial 2 (Ps ≥ 0.162). However, in female participants, there were no associations between pain and CVR indices during either trial (Ps ≥ 0.137). Irrespective of sex, reductions in perceived pain during trial 2 relative to trial 1 were weakly to moderately associated (Ps ≤ 0.038) with reductions in brachial diastolic (ρ = 0.346), mean (ρ = 0.379), and systolic BP (ρ = 0.333); central mean (ρ = 0.400) and systolic BP (ρ = 0.369); and cf-PWV (ρ = 0.526). These findings suggest that 1) there are sex differences in pain modulation of CVR in young adults and 2) habituation blunts pain and CVR during PECO, irrespective of sex.NEW & NOTEWORTHY We demonstrate sex differences in the association between pain perception and cardiovascular reactivity (CVR) during ischemic pain. We also demonstrate habituation to pain and reduced CVR during repeated exposure in a sex-independent manner. Accounting for sex differences and habituation may improve the prognostic utility of CVR.

Six months of unsupervised exercise training lowers blood pressure during moderate, but not vigorous, aerobic exercise in adults with well-healed burn injuries.

Exercise training reduces cardiovascular disease risk, partly due to arterial blood pressure (BP) lowering at rest and during fixed-load exercise. However, it is unclear whether exercise training can reduce BP at rest and during exercise in adults with well-healed burn injuries. Therefore, the purpose of this investigation was to test the hypothesis that 6 mo of unsupervised exercise training reduces BP at rest and during lower-body cycle ergometry in adults with well-healed burn injuries. Thirty-nine adults (28 with well-healed burn injuries and 11 controls) completed 6 mo of unsupervised, progressive exercise training including endurance, resistance, and high-intensity interval components. Before and after exercise training, we measured BP at rest, during fixed-load submaximal exercise (50 and 75 W), during fixed-intensity submaximal exercise (40% and 70% of V̇o2peak), and during maximal exercise on a lower-body cycle ergometer. We compared cardiovascular variables using two-way ANOVA (group × pre/postexercise training [repeated factor]). Adults with well-healed burn injuries had higher diastolic BP at rest (P = 0.04), which was unchanged by exercise training (P = 0.26). Exercise training reduced systolic, mean, and diastolic BP during fixed-load cycling exercise at 75 W in adults with well-healed burn injuries (P ≤ 0.03 for all), but not controls (P ≥ 0.67 for all). Exercise training also reduced mean and diastolic BP during exercise at 40% (P ≤ 0.02 for both), but not at 70% (P ≥ 0.18 for both), of V̇o2peak. These data suggest that a 6-mo unsupervised exercise training program lowers BP during moderate, but not vigorous, aerobic exercise in adults with well-healed burn injuries.NEW & NOTEWORTHY Adults with well-healed burn injuries have greater cardiovascular disease morbidity and all-cause mortality compared with nonburn-injured adults. We found that exercise training reduced blood pressure (BP) during fixed-load cycling at 75 W and during moderate, but not vigorous, intensity cycling exercise in adults with well-healed burn injuries. These data suggest that 6 mo of unsupervised exercise training provides some degree of cardioprotection by reducing BP responses during submaximal exercise in well-healed burn-injured adults.

Low-dose morphine reduces pain perception and blood pressure, but not muscle sympathetic outflow, responses during the cold pressor test.

Our knowledge about how low-dose (analgesic) morphine affects autonomic cardiovascular regulation is primarily limited to animal experiments. Notably, it is unknown if low-dose morphine affects human autonomic cardiovascular responses during painful stimuli in conscious humans. Therefore, we tested the hypothesis that low-dose morphine reduces perceived pain and subsequent sympathetic and cardiovascular responses in humans during an experimental noxious stimulus. Twenty-nine participants (14 females/15 males; 29 ± 6 yr; 26 ± 4 kg·m-2, means ± SD) completed this randomized, crossover, placebo-controlled trial during two laboratory visits. During each visit, participants completed a cold pressor test (CPT; hand in ∼0.4°C ice bath for 2 min) before and ∼35 min after drug/placebo administration (5 mg iv morphine or saline). We compared pain perception (100 mm visual analog scale), muscle sympathetic nerve activity (MSNA; microneurography; 14 paired recordings), and beat-to-beat blood pressure (BP; photoplethysmography) between trials (at both pre- and postdrug/placebo time points) using paired, two-tailed t tests. Before drug/placebo infusion, perceived pain (P = 0.92), ΔMSNA burst frequency (n = 14, P = 0.21), and Δmean BP (P = 0.39) during the CPT were not different between trials. After the drug/placebo infusion, morphine versus placebo attenuated perceived pain (morphine: 43 ± 20 vs. placebo: 57 ± 24 mm, P < 0.001) and Δmean BP (morphine: 10 ± 7 vs. placebo: 13 ± 8 mmHg, P = 0.003), but not ΔMSNA burst frequency (morphine: 10 ± 11 vs. placebo: 13 ± 11 bursts·min-1, P = 0.12), during the CPT. Reductions in pain perception and Δmean BP were only weakly related (r = 0.34, P = 0.07; postmorphine CPT minus postplacebo CPT). These data provide valuable information regarding how low-dose morphine affects autonomic cardiovascular responses during an experimental painful stimulus.NEW & NOTEWORTHY In this randomized, crossover, placebo-controlled trial, we found that low-dose morphine administration reduced pain perception and blood pressure responses during the cold pressor test via attenuated increases in heart rate and cardiac output. We also determined that muscle sympathetic outflow responses during the cold pressor test seem to be unaffected by low-dose morphine administration. Finally, our exploratory analysis suggests that biological sex does not influence morphine-induced antinociception in healthy adults.

Adults with well-healed burn injuries have lower pulmonary function values decades after injury.

Sub-acute (e.g., inhalation injury) and/or acute insults sustained during a severe burn injury impairs pulmonary function. However, previous work has not fully characterized pulmonary function in adults with well-healed burn injuries decades after an injury. Therefore, we tested the hypothesis that adults with well-healed burn injuries have lower pulmonary function years after recovery. Our cohort of adults with well-healed burn-injuries (n = 41) had a lower forced expiratory volume in one second (Burn: 93 ± 16 vs. Control: 103 ± 10%predicted, mean ± SD; d = 0.60, p = 0.04), lower maximal voluntary ventilation (Burn: 84 [71-97] vs. Control: 105 [94-122] %predicted, median [IQR]; d = 0.84, p < 0.01), and a higher specific airway resistance (Burn: 235 ± 80 vs. Control: 179 ± 40%predicted, mean ± SD; d = 0.66, p = 0.02) than non-burned control participants (n = 12). No variables were meaningfully influenced by having a previous inhalation injury (d ≤ 0.44, p ≥ 0.19; 13 of 41 had an inhalation injury), the size of the body surface area burned (R2  ≤ 0.06, p ≥ 0.15; range of 15%-88% body surface area burned), or the time since the burn injury (R2  ≤ 0.04, p ≥ 0.22; range of 2-50 years post-injury). These data suggest that adults with well-healed burn injuries have lower pulmonary function decades after injury. Therefore, future research should examine rehabilitation strategies that could improve pulmonary function among adults with well-healed burn injuries.