Helen E. Wood

Dyspnea on exertion in obese men.

Recently, we reported that dyspnea on exertion is strongly associated with an increased oxygen cost of breathing in otherwise healthy obese women; the mechanism of dyspnea on exertion in obese men is unknown. Obese men underwent measurements of body composition, fat distribution, pulmonary function, steady state and maximal graded cycle ergometry, and oxygen cost of breathing. Nine men (34 ± 8 years, 35 ± 4 BMI) with ratings of perceived breathlessness of ≤2 during cycling, and ten men (36 ± 9 years, 38 ± 5 BMI) with ratings of perceived breathlessness ≥4 were studied (ratings of perceived breathlessness: 1.8 ± 0.4 vs. 4.7 ± 0.8, respectively; p<0.0001). Groups had only minor differences in fat distribution, pulmonary function, and steady state exercise. There was no association between ratings of perceived breathlessness and oxygen cost of breathing; but ratings of perceived breathlessness was strongly correlated with ratings of perceived exertion (RPE, rho=0.87, p<0.0001). The differences in exercise intensity, ventilatory demand, cardiovascular conditioning and/or the quality of respiratory sensation did not appear to play a role in the development of dyspnea on exertion. The mechanism of dyspnea on exertion in obese men seems unrelated to the oxygen cost of breathing.

Exertional dyspnea in mitochondrial myopathy: clinical features and physiological mechanisms

Exertional dyspnea limits exercise in some mitochondrial myopathy (MM) patients, but the clinical features of this syndrome are poorly defined, and its underlying mechanism is unknown. We evaluated ventilation and arterial blood gases during cycle exercise and recovery in five MM patients with exertional dyspnea and genetically defined mitochondrial defects, and in four control subjects (C). Patient ventilation was normal at rest. During exercise, MM patients had low Vo(2peak) (28 ± 9% of predicted) and exaggerated systemic O(2) delivery relative to O(2) utilization (i.e., a hyperkinetic circulation). High perceived breathing effort in patients was associated with exaggerated ventilation relative to metabolic rate with high VE/VO(2peak), (MM = 104 ± 18; C = 42 ± 8, P ≤ 0.001), and Ve/VCO(2peak)(,) (MM = 54 ± 9; C = 34 ± 7, P ≤ 0.01); a steeper slope of increase in ΔVE/ΔVCO(2) (MM = 50.0 ± 6.9; C = 32.2 ± 6.6, P ≤ 0.01); and elevated peak respiratory exchange ratio (RER), (MM = 1.95 ± 0.31, C = 1.25 ± 0.03, P ≤ 0.01). Arterial lactate was higher in MM patients, and evidence for ventilatory compensation to metabolic acidosis included lower Pa(CO(2)) and standard bicarbonate. However, during 5 min of recovery, despite a further fall in arterial pH and lactate elevation, ventilation in MM rapidly normalized. These data indicate that exertional dyspnea in MM is attributable to mitochondrial defects that severely impair muscle oxidative phosphorylation and result in a hyperkinetic circulation in exercise. Exaggerated exercise ventilation is indicated by markedly elevated VE/VO(2), VE/VCO(2), and RER. While lactic acidosis likely contributes to exercise hyperventilation, the fact that ventilation normalizes during recovery from exercise despite increasing metabolic acidosis strongly indicates that additional, exercise-specific mechanisms are responsible for this distinctive pattern of exercise ventilation.

SHORT- AND LONG-TERM MODULATION OF THE EXERCISE VENTILATORY RESPONSE

The importance of adaptive control strategies (modulation and plasticity) in the control of breathing during exercise has become recognized only in recent years. In this review, we discuss new evidence for modulation of the exercise ventilatory response in humans, specifically, short- and long-term modulation. Short-term modulation is proposed to be an important regulatory mechanism that helps maintain blood gas homeostasis during exercise.

Short-term modulation of the exercise ventilatory response in older men

During exercise with added dead space (DS), the exercise ventilatory response (DeltaV(E)/ DeltaV(CO(2))) is augmented in younger men, via short-term modulation (STM) of the exercise ventilatory response. We hypothesized that STM would be diminished or absent in older men due to age-related changes in respiratory function and ventilatory control. Men were studied at rest and during cycle exercise with and without added DS. DeltaV(E)/ DeltaV(CO(2)) increased progressively with increasing DS volume (p<0.01), such that CO(2) was not retained with added DS versus without. Hence, the increase in DeltaV(E)/ DeltaV(CO(2)) was not due to increased chemoreceptor feedback from rest to exercise. Increasing exercise intensity diminished the DeltaV(E)/ DeltaV(CO(2)) (p<0.01), and the size of this effect varied by DS volume (p<0.05). We conclude that STM of the exercise ventilatory response is robust in older men; hence, despite age-related changes in lung function and ventilatory control, the exercise ventilatory response can still adapt to increased DS, in order to maintain isocapnia during exercise relative to rest.

Short-term modulation of the exercise ventilatory response in younger and older women.

The exercise ventilatory response (EVR; defined as the slope of the relationship between ventilation and CO(2) production) is reversibly augmented within a single exercise trial with increased respiratory dead space (DS) in both younger (Wood, H.E., Mitchell, G.S., Babb, T.G., 2008. Short-term modulation of the exercise ventilatory response in young men. J. Appl. Physiol. 104, 244-252) and older (Wood, H.E., Mitchell, G.S., Babb, T.G., 2010. Short-term modulation of the exercise ventilatory response in older men. Respir. Physiol. Neurobiol. 173, 37-46) men. The neural mechanism accounting for this augmentation is known as short-term modulation (STM) of the EVR. Since the effects of female sex hormones on STM are unknown, we examined the capacity for STM in healthy adult women of two age groups; nine younger (29±3 yrs, eumenorrheic) and seven older (69±3 yrs, postmenopausal) women were studied at rest and during cycle exercise (10 W, 30 W; not randomized) in control conditions and with added external DS (200 mL, 400 mL; randomized). Within groups, the main effects of DS and work rate on EVR were analyzed with a two-way repeated measures ANOVA; EVR comparisons between groups were made with unpaired t-tests. In both groups, EVR increased progressively with increasing DS volume (e.g. at 10 W 31±4 and 35±6 in control, 40±11 and 40±6 with 200 mL, 48±12 and 49±11 with 400 mL DS in younger and older women, respectively). In younger women, the effects of DS on EVR differed between work rates (significant interaction, p<0.05), although this was not the case for older women. In both groups, [Formula: see text] regulation was similar between DS and control; hence, increased EVR was not due to altered chemoreceptor feedback from rest to exercise. EVR with and without added DS did not differ between age groups. We conclude that the capacity for STM of the EVR with added DS is similar in healthy younger and older women.

Breathing mechanics during exercise with added dead space reflect mechanisms of ventilatory control

Small increases in external dead space (V(D)) augment the exercise ventilatory response via a neural mechanism known as short-term modulation (STM). We hypothesized that breathing mechanics would differ during exercise, increased V(D) and STM. Men were studied at rest and during cycle exercise (10-50W) without (Control) and with added V(D) (200-600ml). With added V(D), V(T) increased via increased end-inspiratory lung volume (EILV), with no change in end-expiratory lung volume (EELV), indicating recruitment of inspiratory muscles only. With exercise, V(T) increased via both decreased EELV and increased EILV, indicating recruitment of both expiratory and inspiratory muscles. A significant interaction between the effects of exercise and V(D) on mean inspiratory flow indicated that the augmented exercise ventilatory response with added V(D) (i.e. STM) resulted from increased drive to the inspiratory muscles. These results reveal different patterns of respiratory muscle recruitment among experimental conditions. Hence, we conclude that fundamental differences exist in the neural control of ventilatory responses during exercise, increased V(D) and STM.

Ventilatory responses to exercise and hypercapnia following 18 days of head-down rest.

INTRODUCTION The effects of head-down rest (HDR) and microgravity on cardiovascular control have been widely studied; however, their effects on ventilatory control are less clear. An increased ventilatory response to exercise and/or to hypercapnia (HCVR) could cause significantly increased ventilatory demand and/or dyspnea, and thus limit the ability of flight crew to perform high-intensity exercise during or after spaceflight. Based on limited previous studies, we hypothesized that the ventilatory response to exercise would be increased, while the HCVR would be decreased after HDR. METHODS In 21 healthy subjects, ventilatory responses to submaximal exercise and to hypercapnia were tested before and immediately after 18 d of HDR. Subjects were randomly assigned to either daily supine cycle exercise (Exercise group; N = 14, 2 women) or no exercise (Rest group; N = 7, 1 woman) during HDR. RESULTS The exercise ventilatory response (DeltaV(E)/DeltaV(CO2)) and the HCVR were unchanged following HDR in both groups. However, ventilation was significantly elevated after HDR at rest, during submaximal exercise, and while breathing 6% CO2. End-tidal P(CO2) was significantly reduced at rest, during submaximal exercise, and while breathing 3% CO2, indicating a decrease in the CO2 set point. DISCUSSION Although HDR had no effect on the ventilatory responses to exercise and hypercapnia, the CO2 set point appeared to be reduced, suggesting an increase in drive to breathe that occurred regardless of whether or not subjects undertook exercise during HDR. These preliminary results indicate that further study of the effects of HDR on ventilatory control is warranted.