Joyner, Michael J.

Background. Previous studies have demonstrated that men are more likely than women to slow in the marathon (footrace). This study investigated whether the sex difference in pacing occurs for a shorter race distance. Materials & Methods. Data were acquired from the Bolder Boulder 10 km road race for the years 2008–2013, which encompassed 191,693 performances. There were two pacing measures, percentage change in pace of the first 3 miles relative to the final 3.2 miles and percentage change in pace of the first mile relative to the final 5.2 miles. Pacing was analyzed as a continuous variable and as two categorical variables, as follows: “maintain the pace,” defined as slowing <5% and “marked slowing,” defined as slowing ≥10%. Results. Among the fastest ( men < 48:40; women < 55:27) and second fastest ( men < 53:54; women < 60:28) sex-specific finishing time sextiles, men slowed significantly more than women with both pacing measures, but there were no consistently significant sex differences in pacing among the slower four sextiles. For the fastest sextile, the odds for women were 1.96 (first pacing measure) and 1.36 (second measure) times greater than men to maintain the pace. For the fastest sextile, the odds for women were 0.46 (first measure) and 0.65 (second measure) times that of men to exhibit marked slowing. Multiple regression indicated that being older was associated with lesser slowing, but the sex difference among faster runners persisted when age was controlled. Conclusions. There was a sex difference in pacing during a 10 km race where glycogen depletion is not typically relevant. These results support the hypothesis that the sex difference in pacing partly reflects a sex difference in decision making.

AbstractThe autonomic nervous system regulates all aspects of normal cardiac function, and is recognized to play a critical role in the pathophysiology of many cardiovascular diseases. As such, the value of neuroscience‐based cardiovascular therapeutics is increasingly evident. This White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology, pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases.

AbstractThis review focuses on how to assess autonomic function in humans including various ways to measure heart rate, catecholamines, and sympathetic neural activity. The need to assess autonomic function is paramount in many experimental paradigms because of the following. (1) Autonomic dysfunction is present in common diseases like hypertension, diabetes and heart failure, and the magnitude of this dysfunction is broadly related to morbidity and mortality in these disorders. (2) The relationship between autonomic dysfunction and morbidity and mortality can be causal. (3) Interventions that modulate or reverse autonomic dysfunction can improve outcomes in the affected patients. The techniques discussed are also frequently used to understand the autonomic response to sympathoexcitatory manoeuvres like exercise, the cold pressor test or mental stress. Because these manoeuvres can engage a variety of sensory and efferent pathways, under some circumstances the physiological responses measured by many of the techniques are directionally similar, in others they are divergent. Thus any investigator seeking to study the autonomic nervous system or its contribution to either normal physiology or pathophysiological conditions must carefully balance a number of considerations to ensure that the right technique is used to address the question of interest.image

Key points We have developed a simple analytical method for quantifying the transduction of sympathetic activity into vascular tone. This method demonstrates that as women age, the transfer of sympathetic nerve activity into vascular tone is increased, so that for a given level of sympathetic activity there is more vasoconstriction. In men, this measure decreases with age. Test–re‐test analysis demonstrated that the new method is a reliable estimate of sympathetic transduction. We conclude that increased sympathetic vascular coupling contributes to the age‐related increase in blood pressure that occurs in women only. This measure is a reliable estimate of sympathetic transduction in populations with high sympathetic nerve activity. Thus, it will provide information regarding whether treatment targeting the sympathetic nervous system, which interrupts the transfer of sympathetic nerve activity into vascular tone, will be effective in reducing blood pressure in hypertensive patients. This may provide insight into which populations will respond to certain types of anti‐hypertensive medication. Abstract Sex and age differences in the sympathetic control of resting blood pressure (BP) may be due to differences in the transduction of sympathetic nerve activity (SNA) into vascular tone. Current methods for dynamically quantifying transduction focus on the relationship between SNA and vasoconstriction during a pressor stimulus, which increases BP and may be contra‐indicated in patients. We describe a simple analytical method for quantifying transduction under resting conditions. We performed linear regression analysis of binned muscle SNA burst areas against diastolic BP (DBP). We assessed whether the slope of this relationship reflects the transduction of SNA into DBP. To evaluate this, we investigated whether this measure captures differences in transduction in different populations. Specifically, we (1) quantified transduction in young men (YM), young women (YW), older men (OM) and postmenopausal women (PMW); and (2) measured changes in transduction during β‐blockade using propranolol in YW, YM and PMW. YM had a greater transduction vs . OM (0.10 ± 0.01 mmHg (% s) −1 , n = 23 vs . 0.06 ± 0.01 mmHg (% s) −1 , n = 18; P = 0.003). Transduction was lowest in YW (0.02 ± 0.01 mmHg (% s) −1 , n = 23) and increased during β‐blockade (0.11 ± 0.01 mmHg (% s) −1 ; P < 0.001). Transduction in PMW (0.07 ± 0.01 mmHg (% s) −1 , n = 23) was greater compared to YW ( P = 0.001), and was not altered during β‐blockade (0.06 ± 0.01 mmHg (% s) −1 ; P = 0.98). Importantly, transduction increased in women with age, but decreased in men. Transduction in women intersected that in men at 55 ± 1.5 years. This measure of transduction captures age‐ and sex‐differences in the sympathetic regulation of DBP and may be valuable in quantifying transduction in disease. In particular, this measure may help target treatment strategies in specific hypertensive subpopulations.

Human studies use varying levels of low-dose (1-4 μg·kg −1 ·min −1 ) dopamine to examine peripheral chemosensitivity, based on its known ability to blunt carotid body responsiveness to hypoxia. However, the effect of dopamine on the ventilatory responses to hypoxia is highly variable between individuals. Thus we sought to determine 1) the dose response relationship between dopamine and peripheral chemosensitivity as assessed by the ventilatory response to hypoxia in a cohort of healthy adults, and 2) potential confounding cardiovascular responses at variable low doses of dopamine. Young, healthy adults ( n = 30, age = 32 ± 1, 24 male/6 female) were given intravenous (iv) saline and a range of iv dopamine doses (1–4 μg·kg −1 ·min −1 ) prior to and throughout five hypoxic ventilatory response (HVR) tests. Subjects initially received iv saline, and after each HVR the dopamine infusion rate was increased by 1 μg·kg −1 ·min −1 . Tidal volume, respiratory rate, heart rate, blood pressure, and oxygen saturation were continuously measured. Dopamine significantly reduced HVR at all doses ( P < 0.05). When subjects were divided into high ( n = 13) and low ( n = 17) baseline chemosensitivity, dopamine infusion (when assessed by dose) reduced HVR in the high group only ( P < 0.01), with no effect of dopamine on HVR in the low group ( P > 0.05). Dopamine infusion also resulted in a reduction in blood pressure (3 μg·kg −1 ·min −1 ) and total peripheral resistance (1–4 μg·kg −1 ·min −1 ), driven primarily by subjects with low baseline chemosensitivity. In conclusion, we did not find a single dose of dopamine that elicited a nadir HVR in all subjects. Additionally, potential confounding cardiovascular responses occur with dopamine infusion, which may limit its usage.