Objective Xenon is an inhalational anesthetic with the potential to improve athletic performance and cardiorespiratory fitness via proposed increases in total blood volume. This study aimed to determine the effect of a four‐week xenon supplementation protocol on total blood volume, maximal oxygen uptake (V̇2max) and 3‐kilometre time trial performance in trained individuals. Methods Fourteen subjects (32 ± 12 years; 71% male) were assessed for total blood volume through the carbon monoxide rebreathing method, cardiorespiratory fitness via V̇O2max on a treadmill test, and athletic performance using a 3 km time trial. Following baseline assessments, subjects were matched for sex, age and V̇O2max, and were randomised to 12 sessions of gas inhalation over four weeks (2 minutes of inhalation on 3 days per week); 1) xenon, n = 7 (70% xenon, 21% oxygen, 9% nitrogen) or 2) sham gas, n=7 (7% carbon dioxide, 21% oxygen, 62% nitrogen) dosing. Subjects were blinded to group allocation and all outcomes were re‐assessed following the four‐week dosing period. Within‐group mean differences and 95% confidence intervals for outcomes of interest are presented in Table 1. Differences between the xenon and sham gas group over time were tested using two‐way repeated measures ANOVA and are represented by P values. Results Xenon and sham groups were equal at baseline for all outcomes of interest (Table 1). Twelve subjects completed the four‐week dosing intervention and are included in the analyses; one subject withdrew after a single xenon dose due to nausea and one subject was withdrawn after one week of xenon inhalation due to adverse symptoms during and after dosing which resembled sleep paralysis. Blinding was equally effective between groups; subjects in the xenon group were 65% certain of group allocation, while subjects in the sham group were 63% certain of group allocation. There were no significant differences between xenon or sham gas groups for changes in total blood volume, V̇O2max, or 3 km time trial performance (Table 1). Conclusions Four weeks of xenon inhalation did not result in significant changes in total blood volume, cardiorespiratory fitness or athletic performance in comparison to a sham gas. Given the presence of adverse symptoms in approximately 30% (2 out of 7) subjects and a clear absence of physiological and performance benefits, our findings do not support the use of xenon as a performance enhancing substance. Support or Funding Information This study was supported in part by funding from the Partnership for Clean Competition Research Collaborative. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Background: Individuals with left ventricular (LV) hypertrophy and elevated cardiac biomarkers in middle age are at increased risk for the development of heart failure with preserved ejection fraction. Prolonged exercise training reverses the LV stiffening associated with healthy but sedentary aging; however, whether it can also normalize LV myocardial stiffness in patients at high risk for heart failure with preserved ejection fraction is unknown. In a prospective, randomized controlled trial, we hypothesized that 1-year prolonged exercise training would reduce LV myocardial stiffness in patients with LV hypertrophy. Methods: Forty-six patients with LV hypertrophy (LV septum >11 mm) and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [>40 pg/mL] or high-sensitivity troponin T [>0.6 pg/mL]) were randomly assigned to either 1 year of high-intensity exercise training (n=30) or attention control (n=16). Right-heart catheterization and 3-dimensional echocardiography were performed while preload was manipulated using both lower body negative pressure and rapid saline infusion to define the LV end-diastolic pressure-volume relationship. A constant representing LV myocardial stiffness was calculated from the following: P=S×[Exp {a (V–V 0 )}–1], where “P” is transmural pressure (pulmonary capillary wedge pressure – right atrial pressure), “S” is the pressure asymptote of the curve, “V” is the LV end-diastolic volume index, “V 0 ” is equilibrium volume, and “a” is the constant that characterizes LV myocardial stiffness. Results: Thirty-one participants (exercise group [n=20]: 54±6 years, 65% male; and controls (n=11): 51±6 years, 55% male) completed the study. One year of exercise training increased max by 21% (baseline 26.0±5.3 to 1 year later 31.3±5.8 mL·min –1 ·kg –1 , P <0.0001, interaction P =0.0004), whereas there was no significant change in max in controls (baseline 24.6±3.4 to 1 year later 24.2±4.1 mL·min –1 ·kg –1 , P =0.986). LV myocardial stiffness was reduced (right and downward shift in the end-diastolic pressure-volume relationship; LV myocardial stiffness: baseline 0.062±0.020 to 1 year later 0.031±0.009), whereas there was no significant change in controls (baseline 0.061±0.033 to 1 year later 0.066±0.031, interaction P =0.001). Conclusions: In patients with LV hypertrophy and elevated cardiac biomarkers (stage B heart failure with preserved ejection fraction), 1 year of exercise training reduced LV myocardial stiffness. Thus, exercise training may provide protection against the future risk of heart failure with preserved ejection fraction in such patients. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03476785.

Background: Individuals with left ventricular hypertrophy (LVH) and elevated cardiac biomarkers in middle age are at high risk for the development of heart failure with preserved ejection fraction (HFpEF). However, it is unknown what the pathophysiological underpinnings of this high-risk state may be. We tested the hypothesis that patients with LVH and elevated cardiac biomarkers would demonstrate elevated left ventricular (LV) myocardial stiffness in comparison with healthy controls as a key marker for future HFpEF. Methods: Forty-six patients with LVH (LV septum >11 mm) and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [>40 pg/mL] or troponin T [>0.6 pg/mL]) were recruited, along with 61 age- and sex-matched (by cohort) healthy controls. To define LV pressure-volume relationships, right heart catheterization and 3-dimensional echocardiography were performed while preload was manipulated using lower body negative pressure and rapid saline infusion. Results: There were significant differences in body size, blood pressure, and baseline pulmonary capillary wedge pressure between groups (eg, pulmonary capillary wedge pressure: LVH, 13.4±2.7 versus control, 11.7±1.7 mm Hg, P <0.0001). The LV was less distensible in LVH than in controls (smaller volume for the same filling pressure). When preload was expressed as transmural filling pressure (pulmonary capillary wedge pressure – right atrial pressure), LV myocardial stiffness was nearly 30% greater in LVH than in controls (LVH stiffness constant, 0.053±0.027 versus controls, 0.042±0.020, P =0.028). Conclusions: LV myocardial stiffness in patients with LVH and elevated biomarkers (stage-B HFpEF) is greater than in age- and sex-matched controls and thus appears to represent a transitional state from a normal healthy heart to HFpEF. Although the LV myocardial stiffness of patients with LVH is greater than that of healthy controls at this early stage, further studies are required to clarify whether interventions such as exercise training to improve LV compliance may prevent the full manifestation of the HFpEF syndrome in these high-risk individuals. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT03476785 and NCT02039154.

Background: Moderate intensity exercise is associated with a decreased incidence of atrial fibrillation. However, extensive training in competitive athletes is associated with an increased atrial fibrillation risk. We evaluated the effects of 24 months of high intensity exercise training on left atrial (LA) mechanical and electric remodeling in sedentary, healthy middle-aged adults. Methods: Sixty-one participants (53±5 years) were randomized to 10 months of exercise training followed by 14 months of maintenance exercise or stretching/balance control. Fourteen Masters athletes were added for comparison. Left ventricular (LV) and LA volumes underwent 3D echocardiographic assessment, and signal-averaged electrocardiographs for filtered P-wave duration and atrial late potentials were completed at 0, 10, and 24 months. Extended ambulatory monitoring was performed at 0 and 24 months. Within and between group differences from baseline were compared using mixed-effects model repeated-measures analysis. Results: Fifty-three participants completed the study (25 control, 28 exercise) with 88±11% adherence to assigned exercise sessions. In the exercise group, both LA and LV end diastolic volumes increased proportionately (19% and 17%, respectively) after 10 months of training (peak training load). However, only LA volumes continued to increase with an additional 14 months of exercise training (LA volumes 55%; LV end diastolic volumes 15% at 24 months versus baseline; P <0.0001 for all). The LA:LV end diastolic volumes ratio did not change from baseline to 10 months, but increased 31% from baseline in the Ex group ( P <0.0001) at 24 months, without a change in controls. There were no between group differences in the LA ejection fraction, filtered P-wave duration, atrial late potentials, and premature atrial contraction burden at 24 months and no atrial fibrillation was detected. Compared with Masters athletes, the exercise group demonstrated lower absolute LA and LV volumes, but had a similar LA:LV ratio after 24 months of training. Conclusions: Twenty-four months of high intensity exercise training resulted in LA greater than LV mechanical remodeling with no observed electric remodeling. Together, these data suggest different thresholds for electrophysiological and mechanical changes may exist in response to exercise training, and provide evidence supporting a potential mechanism by which high intensity exercise training leads to atrial fibrillation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02039154.

Background: Chronotropic incompetence (CI) is common in HFpEF and is linked to impaired aerobic capacity. Whether upstream autonomic signaling pathways responsible for raising exercise heart rate (HR) are impaired in HFpEF is unknown. We investigated the integrity of central command and muscle metaboreceptor function, two predominant mechanisms responsible for exertional increases in HR, in HFpEF and senior control subjects. Methods: Fourteen healthy, senior controls (7M,7F) and 20 carefully screened HFpEF patients (8M,12F) underwent cardiopulmonary exercise testing (peak VO 2 ) and static handgrip exercise at 40% of maximal voluntary contraction (MVC) to fatigue with post-exercise circulatory arrest (PECA) for 2 minutes to assess central command and metaboreceptor function respectively. Results: Peak VO 2 (13.1 ± 3.4 vs 22.7 ± 4.0 ml/kg/min; p<0.001) and HR (122 ± 20 vs 155 ± 14 bpm; p<0.001) were lower in HFpEF than senior controls. There were no significant differences in peak HR response during static handgrip between groups (HFpEF vs controls: 90 ± 13 vs 93 ± 10 bpm; p=0.49). Metaboreceptor function defined as mean arterial blood pressure at the end of PECA was also not significantly different between groups. Conclusions: Central command (vagally mediated) and metaboreceptor function (sympathetically mediated) in patients with HFpEF were not different from healthy senior controls despite significantly lower peak whole-body exercise heart rates. These results demonstrate key reflex autonomic pathways regulating exercise heart rate responsiveness are intact in HFpEF.

Women are at increased risk for heart failure with preserved ejection fraction (HFpEF) largely due to higher prevalence of arterial and cardiac stiffening. We were able to identify several subclinical markers of early (stages A and B) HFpEF pathophysiology largely on the basis of exercise blood pressure (BP) response in otherwise healthy middle-aged women. Exercise BP response may be an inexpensive screening tool to identify women at highest risk for developing future HFpEF.

No abstract

Evidence suggests differences between African Americans (AAs) and Caucasian Americans (CAs) in cardiovascular responsiveness to physiological stressors. This study tested the hypothesis that carotid baroreflex (CBR) control of heart rate (HR) and blood pressure is reduced in AAs compared to CAs during exercise. Mean arterial pressure (MAP) and HR were continuously recorded at rest and during leg cycling in 23 non-hypertensive male subjects (12 AA; 11 CA; age 19–26 years). CBR control of HR and MAP was assessed with 5-s pulses of neck pressure (NP, simulated hypotension) and neck suction (NS, simulated hypertension) ranging from +45 to −80 Torr. Across all NS stimuli (−20, −40, −60, −80 Torr) at rest, the AA group demonstrated attenuated CBR-mediated reductions in HR (AA, −8.9 ± 1.9 vs. CA, −14.1 ± 2.3 bpm; P < 0.001) and MAP (AA, −6.4 ± 1 vs. CA, −7.8 ± 0.8 mmHg; P < 0.05). Despite similar gain and magnitude of resetting observed in the modeled stimulus response curves, an attenuation among AAs persisted in HR (AA, −8.2 ± 1.6 vs. CA, −11.8 ± 3 bpm; P < 0.05) and MAP (AA, −6.8 ± 0.9 vs. CA, −8.2 ± 1.1 mmHg; P < 0.05) responses to NS during exercise. No differences in CBR-mediated HR and MAP responses to NP were detected between groups at rest or during exercise. These data suggest impairment in the ability to defend against a hypertensive challenge among AAs during steady-state exercise compared to their CA counterparts.