Joyner, Michael J

AbstractIn this review, we argue that several key features of maximal oxygen uptake (VO2max) should underpin discussions about the biological and reductionist determinants of its interindividual variability: (i) training‐induced increases in VO2max are largely facilitated by expansion of red blood cell volume and an associated improvement in stroke volume, which also adapts independent of changes in red blood cell volume. These general concepts are also informed by cross‐sectional studies in athletes that have very high values for VO2max. Therefore, (ii) variations in VO2max improvements with exercise training are also likely related to variations in these physiological determinants. (iii) All previously untrained individuals will respond to endurance exercise training in terms of improvements in VO2max provided the stimulus exceeds a certain volume and/or intensity. Thus, genetic analysis and/or reductionist studies performed to understand or predict such variations might focus specifically on DNA variants or other molecular phenomena of relevance to these physiological pathways.

Key pointsResearch indicates that individuals may experience a rise (positive responders) or fall (negative responders) in muscle sympathetic nerve activity (MSNA) during mental stress.In this study, we examined the early blood pressure responses (including the peak, time of peak and rate of rise in blood pressure) to mental stress in positive and negative responders.Negative MSNA responders to mental stress exhibit a more rapid rise in diastolic pressure at the onset of the stressor, suggesting a baroreflex‐mediated suppression of MSNA. In positive responders there is a more sluggish rise in blood pressure during mental stress, which appears to be MSNA‐driven.This study suggests that whether MSNA has a role in the pressor response is dependent upon the reactivity of blood pressure early in the task.AbstractResearch indicates that individuals may experience a rise (positive responders) or fall (negative responders) in muscle sympathetic nerve activity (MSNA) during mental stress. The aim was to examine the early blood pressure response to stress in positive and negative responders and thus its influence on the direction of change in MSNA. Blood pressure and MSNA were recorded continuously in 21 healthy young males during 2 min mental stressors (mental arithmetic, Stroop test) and physical stressors (cold pressor, handgrip exercise, post‐exercise ischaemia). Participants were classified as negative or positive responders according to the direction of the mean change in MSNA during the stressor tasks. The peak changes, time of peak and rate of changes in blood pressure were compared between groups. During mental arithmetic negative responders experienced a significantly greater rate of rise in diastolic blood pressure in the first minute of the task (1.3 ± 0.5 mmHg s−1) compared with positive responders (0.4 ± 0.1 mmHg s−1;P = 0.03). Similar results were found for the Stroop test. Physical tasks elicited robust parallel increases in blood pressure and MSNA across participants. It is concluded that negative MSNA responders to mental stress exhibit a more rapid rise in diastolic pressure at the onset of the stressor, suggesting a baroreflex‐mediated suppression of MSNA. In positive responders there is a more sluggish rise in blood pressure during mental stress, which appears to be MSNA‐driven. This study suggests that whether MSNA has a role in the pressor response is dependent upon the reactivity of blood pressure early in the task.

This perspective highlights some of the key contributions of Professor Bengt Saltin (1935–2014) to exercise physiology. The emergence of exercise physiology from work physiology as his career began is discussed as are his contributions in a number of areas. Saltin’s open and question-based style of leadership is a model for the future of our field.

New Findings What is the central question of this study? Is lower body negative pressure a useful surrogate to study white blood cell responses to haemorrhage in humans? What is the main finding and its importance? We found that lower body negative pressure appears to be a useful surrogate to study the early white blood cell mobilization response during blood loss. Hypovolaemia has been associated with an immune response that might be secondary to sympathoexcitation. We tested the hypothesis that simulated hypovolaemia using lower body negative pressure (LBNP) and real hypovolaemia induced via experimental blood loss (BL) cause similar increases in the white blood cell concentration ([WBC]). We measured [WBC] and catecholamine concentrations in 12 men who underwent an LBNP and a BL protocol in a randomized order. We compared 45 mmHg of LBNP with 1000 ml of BL; therefore, [WBC] and catecholamine concentrations were plotted against central venous pressure to obtain stimulus–response relationships using the linear regression line slopes for both protocols. Mean regression line slopes were similar for total [WBC] (LBNP 183 ± 4 μl−1 mmHg−1 versus BL 155 ± 109 μl−1 mmHg−1, P = 0.15), neutrophils (LBNP 110 ± 2 μl−1 mmHg−1 versus BL 96 ± 72 μl−1 mmHg−1, P = 0.15) and lymphocytes (LBNP 65 ± 21 μl−1 mmHg−1 versus BL 59 ± 38 μl−1 mmHg−1, P = 0.90). Mean regression line slopes for adrenaline were similar (LBNP 15 ± 5 pg ml−1 mmHg−1 versus BL 16 ± 4 pg ml−1 mmHg−1, P = 0.84) and were steeper during LBNP for noradrenaline (LBNP 28 ± 6 pg ml−1 mmHg−1 versus BL 9 ± 6 pg ml−1 mmHg−1, P = 0.01). These data indicate that central hypovolaemia elicits a relative leucocytosis with a predominantly neutrophil‐based response. Additionally, our results indicate that LBNP models the stimulus–response relationship between central venous pressure and [WBC] observed during BL.

In humans, intra-arterial ATP infusion in limbs mimics many features of exercise hyperemia. However, it remains unknown whether ATP can evoke the prolonged vasodilation seen during exercise. Therefore, we addressed two questions during a continuous 3-h brachial artery infusion of ATP [20 μg·100 ml forearm volume (FAV) −1 ·min −1 ]: 1) would skeletal muscle blood flow remain robust or wane over time (tachyphylaxis); and 2) would the hyperemic response to moderate-intensity exercise performed during the ATP administration be blunted compared with that during control (saline) infusion. Nine participants (25 ± 1 yr) performed one trial consisting of seven bouts of rhythmic handgrip exercise (20 contractions/min at 20% of maximum), two bouts during saline (control), and five bouts during 180 min of continuous ATP infusion. Five minutes of ATP infusion resulted in a 710% increase in forearm vascular conductance (FVC) from control (4.8 ± 0.77 vs. 35.0 ± 5.7 ml·min −1 ·100 mmHg −1 ·dl FAV −1 , P < 0.05). Contrary to our expectations, FVC did not wane over time with values of 35.0 ± 5.7 and 36.0 ± 7.7 ml·min −1 ·100 mmHg −1 ·dl FAV −1 ( P > 0.05), seen prior to the exercise bouts at 5 vs. 150 min, respectively. During superimposed exercise, FVC increased from 35.0 ± 5.7 to 49.6 ± 5.4 ml·min −1 ·100 mmHg −1 ·dl FAV −1 at 5 min and 36.0 ± 7.7 to 54.5 ± 5.0 at 150 min ( P < 0.05). Our findings demonstrate ATP vasodilation is prolonged over time without tachyphylaxis; however, exercise hyperemia responses remain intact. Our results challenge the metabolic theory of exercise hyperemia, suggesting a disconnect between matching of blood flow and metabolic demand.

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.