Joyner, Michael J

While rapid-onset vasodilation (ROV) has been shown to decrease in older individuals, it is unclear if sex contributes to the decline with aging. We sought to identify if sex-related differences exist in the ROV response to single forearm contractions in young and older adults. Our data suggest sex-related differences are present among older but not young individuals, with women having an attenuated response. These data indicate sex plays a role in decreased vasodilation with aging.

Key points Heart failure patients with reduced ejection fraction (HFrEF) exhibit severe limitations in exercise capacity ( peak). One of the primary peripheral mechanisms suggested to underlie exercise intolerance in HFrEF is excessive locomotor muscle group III/IV afferent feedback; however, this has never been investigated in human heart failure. HFrEF patients and controls performed an incremental exercise test to volitional exhaustion to determine peak with lumbar intrathecal fentanyl or placebo. During exercise, cardiac output, leg blood flow and radial artery and femoral venous blood gases were measured. With fentanyl, compared with placebo, patients with HFrEF achieved a higher peak workload, peak, cardiac output, stroke volume and leg blood flow. These findings suggest that locomotor muscle group III/IV afferent feedback in HFrEF leads to increased systemic vascular resistance, which constrains stroke volume, cardiac output and O2 delivery thereby impairing peak and thus exercise capacity. AbstractTo better understand the underlying mechanisms contributing to exercise limitation in heart failure with reduced ejection fraction (HFrEF), we investigated the influence of locomotor muscle group III/IV afferent inhibition via lumbar intrathecal fentanyl on peak exercise capacity ( peak) and the contributory mechanisms. Eleven HFrEF patients and eight healthy matched controls were recruited. The participants performed an incremental exercise test to volitional exhaustion to determine peak with lumbar intrathecal fentanyl or placebo. During exercise, cardiac output and leg blood flow () were measured via open‐circuit acetylene wash‐in technique and constant infusion thermodilution, respectively. Radial artery and femoral venous blood gases were measured. peak was 15% greater with fentanyl compared with placebo for HFrEF (P < 0.01), while no different in the controls. During peak exercise with fentanyl, cardiac output was 12% greater in HFrEF secondary to significant decreases in systemic vascular resistance and increases in stroke volume compared with placebo (all, P < 0.01). From placebo to fentanyl, leg , and O2 delivery were greater for HFrEF during peak exercise (all, P < 0.01), but not control. These findings indicate that locomotor muscle group III/IV afferent feedback in patients with HFrEF leads to increased systemic vascular resistance, which constrains stroke volume, cardiac output and O2 delivery, thereby impairing peak and thus exercise capacity. These findings have important clinical implications as peak is highly predictive of morbidity and mortality in HF.

Abstract BACKGROUND Studies demonstrate an association between aortic hemodynamics and cognitive function. The impact of pregnancy history on this association is unknown. METHODS Postmenopausal women (age 59 ± 5 years; years since last pregnancy 35 ± 3) with either a history of preeclampsia (PE; n = 34) or a history of a normotensive pregnancy (NP; n = 30) underwent cognitive testing: Letter-Number Sequencing, Digit Span, Trail Making Test, and letter and category fluency. Applanation tonometry was used to derive aortic systolic and diastolic blood pressure and augmentation index. RESULTS Distribution of cognitive scores and aortic hemodynamic measures was similar between the PE and NP groups. Principal component (PC) analysis was used to reduce the 3 aortic hemodynamic measures and the 5 cognitive variables to single summary indices, each representing a weighted average of their respective constituent variables. Using a multivariable linear model based on these PCs that adjusted for pregnancy history and body mass index, the composite index of aortic hemodynamics was associated with the summary cognitive index, whether taking into account a potential interaction with pregnancy history (P = 0.035) or not (P = 0.026) (interaction P = 0.178). Multivariable modeling of individual cognitive tests revealed a differential association for letter fluency by pregnancy history (test for interaction P = 0.023); this score correlated with the aortic hemodynamic index in the PE (partial R2 = 0.20), but not the NP (partial R2 = 0.00) group. CONCLUSIONS Elevated aortic hemodynamics may negatively impact cognitive function in postmenopausal women with specific executive functions, such as letter fluency, being impacted more by a pregnancy history of PE.

ABSTRACT Although over 100 studies and reviews have examined the ergogenic effects of dietary nitrate (NO 3 − ) supplementation in young, healthy men and women, it is unclear if participant and environmental factors modulate the well-described ergogenic effects—particularly relevant factors include biological sex, aerobic fitness, and fraction of inspired oxygen (F i O 2 ) during exercise. To address this limitation, the literature was systematically reviewed for randomized, crossover, placebo-controlled studies reporting exercise performance outcome metrics with NO 3 − supplementation in young, healthy adults. Of the 2033 articles identified, 80 were eligible for inclusion in the meta-analysis. Random-effects meta-analysis demonstrated that exercise performance improved with NO 3 − supplementation compared with placebo ( d = 0.174; 95% confidence interval (CI), 0.120–0.229; P < 0.001). Subgroup analyses conducted on biological sex, aerobic fitness, and F i O 2 demonstrated that the ergogenic effect of NO 3 − supplementation was as follows: 1) not observed in studies with only women ( n = 6; d = 0.116; 95% CI, −0.126 to 0.358; P = 0.347), 2) not observed in well-trained endurance athletes (≥65 mL·kg −1 ·min −1 ; n = 26; d = 0.021; 95% CI, −0.103 to 0.144; P = 0.745), and 3) not modulated by F i O 2 (hypoxia vs normoxia). Together, the meta-analyses demonstrated a clear ergogenic effect of NO 3 − supplementation in recreationally active, young, healthy men across different exercise paradigms and NO 3 − supplementation parameters; however, the effect size of NO 3 − supplementation was objectively small ( d = 0.174). NO 3 − supplementation has more limited utility as an ergogenic aid in participants with excellent aerobic fitness that have optimized other training parameters. Mechanistic research and studies incorporating a wide variety of subjects (e.g., women) are needed to advance the study of NO 3 − supplementation; however, additional descriptive studies of young, healthy men may have limited utility.