The current study examined the contribution of central and peripheral adaptations to changes in maximal oxygen uptake (V̇O) following sprint interval training (SIT). Twenty-three males completed 4 weekly SIT sessions (8 × 20-s cycling bouts at ∼170% of work rate at V̇O, 10-s recovery) for 4 weeks. Following completion of training, the relationship between changes in V̇O and changes in central (cardiac output) and peripheral (arterial-mixed venous oxygen difference (a-vOdiff), muscle capillary density, oxidative capacity, fibre-type distribution) adaptations was determined in all participants using correlation analysis. Participants were then divided into tertiles on the basis of the magnitude of their individual V̇O responses, and differences in central and peripheral adaptations were examined in the top (HI; ∼10 mL·kg·min increase in V̇O, p < 0.05) and bottom (LO; no change in V̇O, p > 0.05) tertiles (n = 8 each). Training had no impact on maximal cardiac output, and no differences were observed between the LO group and the HI group (p > 0.05). The a-vOdiff increased in the HI group only (p < 0.05) and correlated significantly (r = 0.71, p < 0.01) with changes in V̇O across all participants. Muscle capillary density (p < 0.02) and β-hydroxyacyl-CoA dehydrogenase maximal activity (p < 0.05) increased in both groups, with no between-group differences (p > 0.05). Citrate synthase maximal activity (p < 0.01) and type IIA fibre composition (p < 0.05) increased in the LO group only. Collectively, although the heterogeneity in the observed V̇O response following 4 weeks of SIT appears to be attributable to individual differences in systemic vascular and/or muscular adaptations, the markers examined in the current study were unable to explain the divergent V̇O responses in the LO and HI groups.

Endothelial dysfunction and reduced nitric oxide (NO) signaling are key abnormalities leading to skeletal muscle oxygen delivery-utilization mismatch and poor physical capacity in patients with heart failure with reduced ejection fraction (HFrEF). Oral inorganic nitrate supplementation provides an exogenous source of NO that may enhance locomotor muscle function and oxygenation with consequent improvement in exercise tolerance in HFrEF. Thirteen patients (left ventricular ejection fraction ≤40%) were enrolled in a double-blind, randomized crossover study to receive concentrated nitrate-rich (nitrate) or nitrate-depleted (placebo) beetroot juice for 9 days. Low- and high-intensity constant-load cardiopulmonary exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary oxygen uptake, quadriceps muscle oxygenation (near-infrared spectroscopy), and blood lactate concentration. Ten patients completed the study with no adverse clinical effects. Nitrate-rich supplementation resulted in significantly higher plasma nitrite concentration compared with placebo (240 ± 48 vs. 56 ± 8 nM, respectively; P < 0.05). There was no significant difference in the primary outcome of time to exercise intolerance between nitrate and placebo (495 ± 53 vs. 489 ± 58 s, respectively; P > 0.05). Similarly, there were no significant differences in central hemodynamics, arterial blood pressure, pulmonary oxygen uptake kinetics, skeletal muscle oxygenation, or blood lactate concentration from rest to low- or high-intensity exercise between conditions. Oral inorganic nitrate supplementation with concentrated beetroot juice did not present with beneficial effects on central or peripheral components of the oxygen transport pathway thereby failing to improve exercise tolerance in patients with moderate HFrEF.

Resistance exercise is an efficacious stimulus for improving cognitive function in older adults, which may be mediated by the upregulation of blood-borne neurotrophic growth factors (NTFs) like brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1). However, the NTF response to resistance exercise and training in older adults is poorly understood. Therefore, the purpose of this study was to characterize the timing and magnitude of the NTF response following an acute bout of resistance exercise before and after 8 weeks of resistance training. Ten cognitively normal, older adults (ages 60-77 years, five men) were examined. The acute NTF response to resistance exercise was assessed via serum samples drawn at designated time points following exercise. This procedure was then repeated following 8 weeks of resistance training. BDNF increased immediately post-exercise (Δ9% pre-training, Δ11% post-training) then returned to resting levels while IGF-1 remained stable following resistance exercise before and after 8 weeks of resistance training. Basal levels of both NTFs were unaffected by the 8 week training period. We report a transient increase in serum BDNF following a bout of resistance exercise in older adults, which could have implications for the design of interventions seeking to maximize cognitive function in older adults.

The primary objective of this study was to determine whether cardiovascular compensatory response phenotypes exist in the face of a reduced perfusion pressure challenge to exercising muscle oxygen delivery (O2D), and whether these responses might be exercise intensity (EI) dependent. Ten healthy men (19.5 ± 0.4 yr) completed two trials of progressive forearm isometric handgrip exercise to exhaustion (24.5 N increments every 3.5 min) in each of forearm above and below heart level [forearm arterial perfusion pressure (FAPP) difference of 29.5 ± 0.97 mmHg]. At the end of each EI, measurements of forearm blood flow (FBF; ml/min) via brachial artery Doppler and echo ultrasound, mean arterial blood pressure (MAP; mmHg) via finger photoplethysmography, and exercising forearm venous effluent via antecubital vein catheter revealed distinct cardiovascular response groups: n = 6 with compensatory vasodilation vs. n = 4 without compensatory vasodilation. Compensatory vasodilators were able to blunt the perfusion pressure-evoked reduction in submaximal O2D in the arm-above-heart condition, whereas nonvasodilators did not (-22.5 ± 13.6 vs. -65.4 ± 14.1 ml O2/min; P < 0.05), and in combination with being able to increase O2 extraction, nonvasodilators defended submaximal V̇o2 and experienced less of an accumulated submaximal O2D deficit (-80.7 ± 24.7 vs. -219.1 ± 36.0 ml O2/min; P < 0.05). As a result, the compensatory vasodilators experienced less of a compromise to peak EI than nonvasodilators (-24.5 ± 3.5 N vs. -52.1 ± 8.9 N; P < 0.05). In conclusion, in the forearm exercise model studied, vasodilatory response phenotypes exist that determine individual susceptibility to hypoperfusion and the degree to which aerobic metabolism and exercise performance are compromised.

Background Resting right heart catheterization can assess both left heart filling and pulmonary artery (PA) pressures to identify and classify pulmonary hypertension. Although exercise may further elucidate hemodynamic abnormalities, current pulmonary hypertension classifications do not consider the expected interrelationship between PA and left heart filling pressures. This study explored the utility of this relationship to enhance the classification of exercise hemodynamic phenotypes in pulmonary hypertension. Methods and Results Data from 36 healthy individuals (55, 50–60 years, 50% male) and 85 consecutive patients (60, 49–71 years, 48% male) with dyspnea and/or suspected pulmonary hypertension of uncertain etiology were analyzed. Right heart catheterization was performed at rest and during semiupright submaximal cycling. To classify exercise phenotypes in patients, upper 95% CIs were identified from the healthy individuals for the change from rest to exercise in mean PA pressure over cardiac output (ΔmPAP/ΔCO ≤3.2 Wood units [WU]), pulmonary artery wedge pressure over CO (ΔPAWP/ΔCO ≤2 mm Hg/L per minute), and exercise PA pulse pressure over PAWP (PP/PAWP ≤2.5). Among patients with a ΔmPAP/ΔCO ≤3.2 WU, the majority (84%) demonstrated a ΔPAWP/ΔCO ≤2 mm Hg/L per minute, yet 23% demonstrated an exercise PP/PAWP >2.5. Among patients with a ΔmPAP/ΔCO >3.2 WU, 37% had an exercise PP/PAWP >2.5 split between ΔPAWP/ΔCO groups. Patients with normal hemodynamic classification declined from 52% at rest to 36% with exercise. Conclusions The addition of PP/PAWP to classify exercise hemodynamics uncovers previously unrecognized abnormal phenotypes within each ΔmPAP/ΔCO group. Our study refines abnormal exercise hemodynamic phenotypes based on an understanding of the interrelationship between PA and left heart filling pressures.