Smith, Joshua R.

New Findings What is the central question of this study? The goal of this study was to investigate the effect of alterations in tidal volume and alveolar volume on the elevated physiological dead space and the contribution of ventilatory constraints thereof in heart failure patients during submaximal exercise. What is the main finding and its importance? We found that physiological dead space was elevated in heart failure via reduced tidal volume and alveolar volume. Furthermore, the degree of ventilatory constraints was associated with physiological dead space and alveolar volume. AbstractPatients who have heart failure with reduced ejection fraction (HFrEF) exhibit impaired ventilatory efficiency [i.e. greater ventilatory equivalent for carbon dioxide () slope] and elevated physiological dead space (VD/VT). However, the impact of breathing strategy on VD/VT during submaximal exercise in HFrEF is unclear. The HFrEF (n = 9) and control (CTL, n = 9) participants performed constant‐load cycling exercise at similar ventilation (). Inspiratory capacity, operating lung volumes and arterial blood gases were measured during submaximal exercise. Arterial blood gases were used to derive VD/VT, alveolar volume, dead space volume, alveolar ventilation and dead space ventilation. During submaximal exercise, HFrEF patients had greater slope and VD/VT than CTL subjects (P = 0.01). At similar , HFrEF patients had smaller tidal volumes and alveolar volumes (HFrEF 1.11 ± 0.33 litres versus CTL 1.66 ± 0.37 litres; both P ≤ 0.01), whereas dead space volume was not different (P = 0.47). The augmented breathing frequency in HFrEF patients resulted in greater dead space ventilation compared with CTL subjects (HFrEF 15 ± 4 l min−1 versus CTL 10 ± 5 l min−1; P = 0.048). The HFrEF patients exhibited greater increases in expiratory reserve volume and lower inspiratory capacity (as a percentage of predicted) than CTL subjects (both P < 0.05), which were significantly related to VD/VT and alveolar volume in HFrEF patients (all P < 0.03). In HFrEF, the reduced tidal volume and alveolar volume elevate physiological dead space during submaximal exercise, which is worsened in those with the greatest ventilatory constraints. These findings highlight the negative consequences of ventilatory constraints on physiological dead space during submaximal exercise in HFrEF.

It is unknown whether the greater total work of breathing (WOB) with aging is due to greater elastic and/or resistive WOB. We hypothesized that older compared with younger adults would exhibit a greater total WOB at matched ventilations (V̇e) during graded exercise, secondary to greater inspiratory resistive and elastic as well as expiratory resistive WOB. Older (OA: 60 ± 8 yr; n = 9) and younger (YA: 38 ± 7 yr; n = 9) adults performed an incremental cycling test to volitional fatigue. Esophageal pressure, inspiratory (IRV) and expiratory reserve volumes (ERV), expiratory flow limitation (EFL), and ventilatory variables were measured at matched V̇e (i.e., 25, 50, and 75 l/min) during exercise. The inspiratory resistive and elastic as well as expiratory resistive WOB were quantified using the Otis method. At V̇e of 75 l/min, older adults had greater %EFL and larger tidal volumes to inspiratory capacity but smaller relative IRV ( P ≤ 0.03) than younger adults. Older compared with younger adults had greater total WOB at V̇Eof 50 and 75 l/min (OA: 90 ± 43 vs. YA: 49 ± 21 J/min; P < 0.04 for both). At V̇e of 75 l/min, older adults had greater inspiratory elastic and resistive WOB (OA: 44 ± 27 vs. YA: 24 ± 22 and OA: 23 ± 15 vs. YA: 11 ± 3 J/min, respectively, P < 0.03 for both) and expiratory resistive WOB (OA: 23 ± 19 vs. YA: 14 ± 9 J/min, P = 0.02) than younger adults. These data demonstrate that aging-induced pulmonary alterations result in greater inspiratory elastic and resistive as well as expiratory resistive WOB, which may have implications for the integrated response during exercise.NEW & NOTEWORTHY Aging-induced changes to the pulmonary system result in increased work of breathing (WOB) during exercise. However, it is not known whether this higher WOB with aging is due to differences in elastic and/or resistive WOB. Herein, we demonstrate that older adults exhibited greater inspiratory elastic and resistive as well as expiratory resistive WOB during exercise.

AbstractAimIn contrast to knowledge that heart failure (HF) patients demonstrate peak exercise uncoupling across ventilation, gas exchange and cardiac haemodynamics, whether this dyssynchrony follows that at the exercise on‐transition is unclear. This study tested whether exercise on‐transition temporal lag for ventilation relative to gas exchange and oxygen pulse (O2pulse) couples with effects from abnormal pulmonary gaseous oxygen store (O2store) contributions to O2 to interdependently precipitate persistently elevated ventilatory demand and low oxidative metabolic capacity in HF.MethodsBeat‐to‐beat HR and breath‐to‐breath ventilation and gas exchange were continuously acquired in HF (N = 9, ejection fraction = 30 ± 9%) and matched controls (N = 10) during square‐wave ergometry at 60% O2peak (46 ± 14 vs 125 ± 54‐W, P < .001). Temporal responses across E, O2 and O2pulse were assessed for the exercise on‐transition using single exponential model Phase II on‐kinetic time constants (τ = time to reach 63% steady‐state rise). Breath‐to‐breath gas fractions and respiratory flows were used to determine O2stores.ResultsHF vs controls: τ for E (137 ± 93 vs 74 ± 40‐seconds, P = .03), O2 (60 ± 40 vs 23 ± 5‐seconds, P = .03) and O2pulse (28 ± 18 vs 23 ± 15‐seconds, P = .59). Within HF, τ for E differed from O2pulse (P < .02), but not O2. Exercise E rise (workload indexed) differed in HF vs controls (545 ± 139 vs 309 ± 88‐mL min−1 W−1, P < .001). Exercise on‐transition O2store depletion in HF exceeded controls, generally persisting to end‐exercise.ConclusionThese data suggest HF demonstrated exercise on‐transition O2store depletion (high O2store contribution to O2) coupled with dyssynchronous E, O2 and O2pulse kinetics—not attributable to prolonged cardiac haemodynamics. Persistent high ventilatory demand and low oxidative metabolic capacity in HF may be precipitated by physiological uncoupling occurring within the exercise on‐transition.

New Findings What is the central question of this study? Premenopausal women have an attenuated inspiratory muscle metaboreflex‐induced increase in arterial blood pressure compared with men. It is unclear whether sympathetic vasomotor outflow during dynamic exercise with increased inspiratory muscle activation is less in young women than in men. What is the main finding and its importance? The magnitude of increased sympathetic vasomotor outflow during leg cycling with inspiratory resistance was smaller in women than in men. Less sympathetic vasomotor outflow with inspiratory muscle metaboreflex activation could be one of the mechanisms for the attenuated inspiratory muscle‐induced metaboreflex during exercise in young women. AbstractWe compared changes in muscle sympathetic nerve activity (MSNA) and cardiovascular variables during leg cycle exercise with increased inspiratory muscle resistance in men and women. We hypothesized that sympathetic vasomotor outflow during exercise with increased inspiratory resistance would be attenuated in young women compared with age‐matched men. Eight women and seven men completed the study. The subjects performed two 10 min exercise bouts at 40% peak oxygen uptake using a cycle ergometer in a semirecumbent position [spontaneous breathing for 5 min and voluntary hyperventilation with or without inspiratory resistive breathing for 5 min (breathing frequency 50 breaths min−1 with a 50% duty cycle; inspiratory resistance 30% of maximal inspiratory pressure)]. Mean arterial blood pressure (MAP) was acquired using finger photoplethysmography. The MSNA was recorded via microneurography of the right median nerve at the cubital fossa. During leg cycle exercise with inspiratory resistive breathing, MSNA burst frequency was increased, accompanied by an increase in MAP in both men and women. Women, compared with men, had less of an increase in MAP (women +22.8 ± 12.3 mmHg versus men +32.2 ± 5.4 mmHg; P < 0.05) and MSNA burst frequency (women +9.6 ± 2.9 bursts min−1 versus men +14.6 ± 6.4 bursts min−1; P < 0.05). These results suggest that the attenuated inspiratory muscle‐induced metaboreflex during exercise in young women is attributable, in part, to a lesser sympathetic vasomotor outflow compared with men.

Development of late-onset respiratory diseases is associated with elevated 8-isoprostane, a marker of oxidative stress, in the airways. However, sex differences exist in development of these diseases. Using an exhaustive exercise bout as a physiological stressor may elucidate whether there is a sex difference with aging in pre- to postexercise airway 8-isoprostane generation. The purpose of this study was to determine whether older women exhibit a greater airway 8-isoprostane response to exhaustive exercise compared with older men and younger controls. Thirty-six individuals completed the study (12 postmenopausal older women (OW) and 12 age-matched older men (OM), 65 ± 4 years of age; and 12 younger controls (YC), 21 ± 2 years of age). Baseline measurements included exhaled breath condensate (EBC) for assessment of airway 8-isoprostane and standard pulmonary function tests (PFTs) to assess forced expiratory volume in 1-s (FEV1), forced vital capacity (FVC), FEV1/FVC, and forced expiratory flow at 25%–75% of FVC. Subjects then performed a peak oxygen uptake test to exhaustion on a cycle ergometer. Immediately postexercise, PFTs and EBC were performed. The generation of airway 8-isoprostane from pre- to postexercise was greater in OW compared with OM and YC (p < 0.01), increasing ∼74% ± 77% in OW, while decreasing in OM (∼12% ± 50%) and YC (∼20.9% ± 30%). The OW exhibited a greater airway 8-isoprostane response to exhaustive exercise compared with OM and YC, which may suggest that sex differences in oxidative stress generation following exhaustive exercise may provide a mechanistic rationale for sex differences in late-onset respiratory diseases.