Repeat exercise normalizes the gas-exchange impairment induced by a previous exercise bout in asthmatic subjects.

Twenty-one subjects with asthma underwent treadmill exercise to exhaustion at a workload that elicited approximately 90% of each subject's maximal O2 uptake (EX1). After EX1, 12 subjects experienced significant exercise-induced bronchospasm [(EIB+), %decrease in forced expiratory volume in 1.0 s = -24.0 +/- 11.5%; pulmonary resistance at rest vs. postexercise = 3.2 +/- 1.5 vs. 8.1 +/- 4.5 cmH2O.l(-1).s(-1)] and nine did not (EIB-). The alveolar-to-arterial Po2 difference (A-aDo2) was widened from rest (9.1 +/- 6.7 Torr) to 23.1 +/- 10.4 and 18.1 +/- 9.1 Torr at 35 min after EX1 in subjects with and without EIB, respectively (P < 0.05). Arterial Po2 (PaO2) was reduced in both groups during recovery (EIB+, -16.0 +/- -13.0 Torr vs. baseline; EIB-, -11.0 +/- 9.4 Torr vs. baseline, P < or = 0.05). Forty minutes after EX1, a second exercise bout was completed at maximal O2 uptake. During the second exercise bout, pulmonary resistance decreased to baseline levels in the EIB+ group and the A-aDo2 and PaO2 returned to match the values seen during EX1 in both groups. Sputum histamine (34.6 +/- 25.9 vs. 61.2 +/- 42.0 ng/ml, pre- vs. postexercise) and urinary 9alpha,11beta-prostaglandin F2 (74.5 +/- 38.6 vs. 164.6 +/- 84.2 ng/mmol creatinine, pre- vs. postexercise) were increased after exercise only in the EIB+ group (P < 0.05), and postexercise sputum histamine was significantly correlated with the exercise PaO2 and A-aDo2 in the EIB+ subjects. Thus exercise causes gas-exchange impairment during the postexercise period in asthmatic subjects independent of decreases in forced expiratory flow rates after the exercise; however, a subsequent exercise bout normalizes this impairment secondary in part to a fast acting, robust exercise-induced bronchodilatory response.

Gas exchange during exercise in habitually active asthmatic subjects.

We determined the relations among gas exchange, breathing mechanics, and airway inflammation during moderate- to maximum-intensity exercise in asthmatic subjects. Twenty-one habitually active (48.2 +/- 7.0 ml.kg(-1).min(-1) maximal O2 uptake) mildly to moderately asthmatic subjects (94 +/- 13% predicted forced expiratory volume in 1.0 s) performed treadmill exercise to exhaustion (11.2 +/- 0.15 min) at approximately 90% of maximal O2 uptake. Arterial O2 saturation decreased to < or =94% during the exercise in 8 of 21 subjects, in large part as a result of a decrease in arterial Po2 (PaO2): from 93.0 +/- 7.7 to 79.7 +/- 4.0 Torr. A widened alveolar-to-arterial Po2 difference and the magnitude of the ventilatory response contributed approximately equally to the decrease in PaO2 during exercise. Airflow limitation and airway inflammation at baseline did not correlate with exercise gas exchange, but an exercise-induced increase in sputum histamine levels correlated with exercise Pa(O2) (negatively) and alveolar-to-arterial Po2 difference (positively). Mean pulmonary resistance was high during exercise (3.4 +/- 1.2 cmH2O.l(-1).s) and did not increase throughout exercise. Expiratory flow limitation occurred in 19 of 21 subjects, averaging 43 +/- 35% of tidal volume near end exercise, and end-expiratory lung volume rose progressively to 0.25 +/- 0.47 liter greater than resting end-expiratory lung volume at exhaustion. These mechanical constraints to ventilation contributed to a heterogeneous and frequently insufficient ventilatory response; arterial Pco2 was 30-47 Torr at end exercise. Thus pulmonary gas exchange is impaired during high-intensity exercise in a significant number of habitually active asthmatic subjects because of high airway resistance and, possibly, a deleterious effect of exercise-induced airway inflammation on gas exchange efficiency.

Fatiguing inspiratory muscle work causes reflex reduction in resting leg blood flow in humans.

1. We recently showed that fatigue of the inspiratory muscles via voluntary efforts caused a time-dependent increase in limb muscle sympathetic nerve activity (MSNA) (St Croix et al. 2000). We now asked whether limb muscle vasoconstriction and reduction in limb blood flow also accompany inspiratory muscle fatigue. 2. In six healthy human subjects at rest, we measured leg blood flow (.Q(L)) in the femoral artery with Doppler ultrasound techniques and calculated limb vascular resistance (LVR) while subjects performed two types of fatiguing inspiratory work to the point of task failure (3-10 min). Subjects inspired primarily with their diaphragm through a resistor, generating (i) 60 % maximal inspiratory mouth pressure (P(M)) and a prolonged duty cycle (T(I)/T(TOT) = 0.7); and (ii) 60 % maximal P(M) and a T(I)/T(TOT) of 0.4. The first type of exercise caused prolonged ischaemia of the diaphragm during each inspiration. The second type fatigued the diaphragm with briefer periods of ischaemia using a shorter duty cycle and a higher frequency of contraction. End-tidal P(CO2) was maintained by increasing the inspired CO(2) fraction (F(I,CO2)) as needed. Both trials caused a 25-40 % reduction in diaphragm force production in response to bilateral phrenic nerve stimulation. 3. .Q(L) and LVR were unchanged during the first minute of the fatigue trials in most subjects; however, .Q(L) subsequently decreased (-30 %) and LVR increased (50-60 %) relative to control in a time-dependent manner. This effect was present by 2 min in all subjects. During recovery, the observed changes dissipated quickly (< 30 s). Mean arterial pressure (MAP; +4-13 mmHg) and heart rate (+16-20 beats min(-1)) increased during fatiguing diaphragm contractions. 4. When central inspiratory motor output was increased for 2 min without diaphragm fatigue by increasing either inspiratory force output (95 % of maximal inspiratory pressure (MIP)) or inspiratory flow rate (5 x eupnoea), .Q(L), MAP and LVR were unchanged; although continuing the high force output trials for 3 min did cause a relatively small but significant increase in LVR and a reduction in .Q(L). 5. When the breathing pattern of the fatiguing trials was mimicked with no added resistance, LVR was reduced and .Q(L) increased significantly; these changes were attributed to the negative feedback effects on MSNA from augmented tidal volume. 6. Voluntary increases in inspiratory effort, in the absence of diaphragm fatigue, had no effect on .Q(L) and LVR, whereas the two types of diaphragm-fatiguing trials elicited decreases in .Q(L) and increases in LVR. We attribute these changes to a metaboreflex originating in the diaphragm. Diaphragm and forearm muscle fatigue showed very similar time-dependent effects on LVR and .Q(L).

Effects of respiratory muscle training versus placebo on endurance exercise performance.

We evaluated the effects of a 5 week (25 sessions); (30-35 min/day, 5 days/week), respiratory muscle training (RMT) program in nine competitive male cyclists. The experimental design included inspiratory resistance strength training (3-5 min/session) and hyperpnea endurance training (30 min/session), a placebo group which used a sham hypoxic trainer (n=8), and three exercise performance tests, including a highly reproducible 8 km time trial test. RMT intensity, measured once a week in terms of accumulated inspiratory pressure and the level of sustainable hyperpnea increased significantly after 5 weeks (+64% and +19%, respectively). The RMT group showed a significant 8% increase in maximal inspiratory pressure (P<0.05) while the placebo group showed only a 3.7% increase (P>0.10). RMT and placebo groups both showed significant increases in the fixed work-rate endurance test performance time (+26% and +16%, respectively) and in the peak work-rate achieved during the incremental maximal oxygen consumption (V(O2)max) test (+9 and +6%). The 8 km time trial performance increased 1.8+/-1.2% (or 15+/-10 sec; P<0.01) in the RMT group with 8 of 9 subjects increasing; the placebo group showed a variable non-significant change in 5 of 8 subjects (-0.3+/-2.7%, P=0.07). The changes observed in these three performance tests were not, however, significantly different between the RMT and placebo groups. Heart rate, ventilation, or venous blood lactate, at equal work-rates during the incremental exercise test or at equal times during the fixed work-rate endurance test were not changed significantly across these exercise trials in either group. We propose that the effect of RMT on exercise performance in highly trained cyclists does not exceed that in a placebo group. Significant placebo and test familiarization effects must be accounted for in experimental designs utilizing performance tests which are critically dependent on volitional effort.

Effects of exhaustive endurance exercise on pulmonary gas exchange and airway function in women.

Seventeen fit women ran to exhaustion (14 +/- 4 min) at a constant speed and grade, reaching 95 +/- 3% of maximal O(2) consumption. Pre- and postexercise lung function, including airway resistance [total respiratory resistance (Rrs)] across a range of oscillation frequencies, was measured, and, on a separate day, airway reactivity was assessed via methacholine challenge. Arterial O(2) saturation decreased from 97.6 +/- 0.5% at rest to 95.1 +/- 1.9% at 1 min and to 92.5 +/- 2.6% at exhaustion. Alveolar-arterial O(2) difference (A-aDO(2)) widened to 27 +/- 7 Torr after 1 min and was maintained at this level until exhaustion. Arterial PO(2) (Pa(O(2))) fell to 80 +/- 8 Torr at 1 min and then increased to 86 +/- 9 Torr at exhaustion. This increase in Pa(O(2)) over the exercise duration occurred due to a hyperventilation-induced increase in alveolar PO(2) in the presence of a constant A-aDO(2). Arterial O(2) saturation fell with time because of increasing temperature (+2.6 +/- 0.5 degrees C) and progressive metabolic acidosis (arterial pH: 7.39 +/- 0.04 at 1 min to 7.26 +/- 0.07 at exhaustion). Plasma histamine increased throughout exercise but was inversely correlated with the fall in Pa(O(2)) at end exercise. Neither pre- nor postexercise Rrs, frequency dependence of Rrs, nor diffusing capacity for CO correlated with the exercise A-aDO(2) or Pa(O(2)). Although several subjects had a positive or borderline hyperresponsiveness to methacholine, this reactivity did not correlate with exercise-induced changes in Rrs or exercise-induced arterial hypoxemia. In conclusion, regardless of the degree of exercise-induced arterial hypoxemia at the onset of high-intensity exercise, prolonging exercise to exhaustion had no further deleterious effects on A-aDO(2), and the degree of gas exchange impairment was not related to individual differences in small or large airway function or reactivity.

Effects of respiratory muscle work on exercise performance.

The normal respiratory muscle effort at maximal exercise requires a significant fraction of cardiac output and causes leg blood flow to fall. We questioned whether the high levels of respiratory muscle work experienced in heavy exercise would affect performance. Seven male cyclists [maximal O(2) consumption (VO(2)) 63 +/- 5 ml. kg(-1). min(-1)] each completed 11 randomized trials on a cycle ergometer at a workload requiring 90% maximal VO(2). Respiratory muscle work was either decreased (unloading), increased (loading), or unchanged (control). Time to exhaustion was increased with unloading in 76% of the trials by an average of 1.3 +/- 0.4 min or 14 +/- 5% and decreased with loading in 83% of the trials by an average of 1.0 +/- 0.6 min or 15 +/- 3% compared with control (P < 0.05). Respiratory muscle unloading during exercise reduced VO(2), caused hyperventilation, and reduced the rate of change in perceptions of respiratory and limb discomfort throughout the duration of exercise. These findings demonstrate that the work of breathing normally incurred during sustained, heavy-intensity exercise (90% VO(2)) has a significant influence on exercise performance. We speculate that this effect of the normal respiratory muscle load on performance in trained male cyclists is due to the associated reduction in leg blood flow, which enhances both the onset of leg fatigue and the intensity with which both leg and respiratory muscle efforts are perceived.

Effect of exercise-induced arterial O2 desaturation on VO2max in women.

PURPOSE: We have recently reported that many healthy habitually active women experience exercise induced arterial hypoxemia (EIAH). We questioned whether EIAH affected VO2max in this population and whether the effect was similar to that reported in men. METHODS: Twenty-five healthy young women with widely varying fitness levels (VO2max, 56.7 +/- 1.5 mL x kg(-1) x min(-1); range: 41-70 mL x kg(-1) x min(-1)) and normal resting lung function performed two randomized incremental treadmill tests to VO2max (FIO2: 0.21 or 0.26) during the follicular phase of their menstrual cycle. Arterial blood samples were taken at rest and near the end of each workload during the normoxic test. RESULTS: During room air breathing at VO2max, SaO2 decreased to 91.8 +/- 0.4% (range 87-95%). With 0.26 FIO2, SaO2, at VO2max remained near resting levels and averaged 96.8 +/- 0.1% (range 96-98%). When arterial O2 desaturation was prevented via increased FIO2, VO2max increased in 22 of the 25 subjects and in proportion to the degree of arterial O2 desaturation experienced in normoxia (r = 0.88). The improvement in VO2max when systemic normoxia was maintained averaged 6.3 +/- 0.3% (range 0 to +15%) and the slope of the relationship was approximately 2% increase in VO2max for every 1% decrement in the arterial oxygen saturation below resting values. About 75% of the increase in VO2max resulted from an increase in VO2 at a fixed maximal work rate and exercise duration, and the remainder resulted from an increase in maximal work rate. CONCLUSIONS: These data demonstrate that even small amounts of EIAH (i.e., >3% delta SaO2 below rest) have a significant detrimental effect on VO2max in habitually active women with a wide range of VO2max. In combination with our previous findings documenting EIAH in females, we propose that inadequate pulmonary structure/function in many habitually active women serves as a primary limiting factor in maximal O2 transport and utilization during maximal exercise.

Airway obstruction during exercise and isocapnic hyperventilation in asthmatic subjects.

We compared pulmonary mechanics measured during long-term exercise (LTX = 20 min) with long-term isocapnic hyperventilation (LTIH = 20 min) in the same asthmatic individuals (n = 6). Peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV(1)) decreased during LTX (-19.7 and -22.0%, respectively) and during LTIH (-6.66 and 10. 9%, respectively). In contrast, inspiratory pulmonary resistance (RL(I)) was elevated during LTX (57.6%) but not during LTIH (9.62%). As expected, airway function deteriorated post-LTX and post-LTIH (FEV(1) = -30.2 and -21.2%; RL(I) = 111.8 and 86.5%, respectively). We conclude that the degree of airway obstruction observed during LTX is of a greater magnitude than that observed during LTIH. Both modes of hyperpnea induced similar levels of airway obstruction in the posthyperpnea period. However, the greater airway obstruction during LTX suggests that a different process may be responsible for the changes in airway function during and after the two modes of hyperpnea. This finding raises questions about the equivalency of LTIH and LTX in the study of airway function during exercise-induced asthma.

Influence of respiratory muscle work on VO(2) and leg blood flow during submaximal exercise.

The work of breathing (W(b)) normally incurred during maximal exercise not only requires substantial cardiac output and O(2) consumption (VO(2)) but also causes vasoconstriction in locomotor muscles and compromises leg blood flow (Q(leg)). We wondered whether the W(b) normally incurred during submaximal exercise would also reduce Q(leg). Therefore, we investigated the effects of changing the W(b) on Q(leg) via thermodilution in 10 healthy trained male cyclists [maximal VO(2) (VO(2 max)) = 59 +/- 9 ml. kg(-1). min(-1)] during repeated bouts of cycle exercise at work rates corresponding to 50 and 75% of VO(2 max). Inspiratory muscle work was 1) reduced 40 +/- 6% via a proportional-assist ventilator, 2) not manipulated (control), or 3) increased 61 +/- 8% by addition of inspiratory resistive loads. Increasing the W(b) during submaximal exercise caused VO(2) to increase; decreasing the W(b) was associated with lower VO(2) (DeltaVO(2) = 0.12 and 0.21 l/min at 50 and 75% of VO(2 max), respectively, for approximately 100% change in W(b)). There were no significant changes in leg vascular resistance (LVR), norepinephrine spillover, arterial pressure, or Q(leg) when W(b) was reduced or increased. Why are LVR, norepinephrine spillover, and Q(leg) influenced by the W(b) at maximal but not submaximal exercise? We postulate that at submaximal work rates and ventilation rates the normal W(b) required makes insufficient demands for VO(2) and cardiac output to require any cardiovascular adjustment and is too small to activate sympathetic vasoconstrictor efferent output. Furthermore, even a 50-70% increase in W(b) during submaximal exercise, as might be encountered in conditions where ventilation rates and/or inspiratory flow resistive forces are higher than normal, also does not elicit changes in LVR or Q(leg).

Assessment of nitric oxide formation during exercise.

We measured the end-tidal plateau in exhaled NO concentration (CETNO) by chemiluminescence and calculated the product of V E and CETNO (V NO) in nine healthy subjects at rest and during three intensities of cycling exercise (30%, 60%, and 90% V O2max), two levels of hyperventilation (V E = 42.8 +/- 9.1 L/min and 84.2 +/- 6. 6 L/min), and during breathing of hypoxic gas mixtures (five subjects, FIO2 = 14%) at rest and during exercise at 90% V O2max. Immediately after each trial we also measured exhaled [NO] at constant expiratory flow rates ([NO]CF) of 46 ml/s and 950 ml/s, utilizing added expiratory resistance to increase mouth pressure and close the velum (Silkoff and colleagues, Am. J. Respir. Crit. Care Med. 1997;155:260). CETNO decreased and V NO increased above resting levels with increasing exercise intensity during hyperventilation and during hypoxic exercise (p < 0.05). [NO]CF, measured at either 46 ml/s or 950 ml/s, did not increase under any of the conditions investigated (exercise, hyperventilation, or hypoxia). Venous blood from seven of the subjects was sampled for the measurement of plasma [NO3-]. Resting plasma [NO3-] averaged 42.5 +/- 14.7 micromol/L, with no change during exercise, hyperventilation, or hypoxia. On the basis of these results we conclude that reported increases in V NO do not reflect an exercise-induced augmentation of systemic and/or airway NO production. Rather, the increases in V NO during exercise or hyperventilation are a function of high airflow rates, which reduce the luminal [NO]. This decreases the concentration gradient for NO between the alveolar space and pulmonary capillary blood, which results in a decrease in the fraction of NO taken up by the blood and an increase in the volume of NO recovered in the exhaled air (V NO).

Role of expiratory flow limitation in determining lung volumes and ventilation during exercise.

We determined the role of expiratory flow limitation (EFL) on the ventilatory response to heavy exercise in six trained male cyclists [maximal O2 uptake = 65 +/- 8 (range 55-74) ml. kg-1. min-1] with normal lung function. Each subject completed four progressive cycle ergometer tests to exhaustion in random order: two trials while breathing N2O2 (26% O2-balance N2), one with and one without added dead space, and two trials while breathing HeO2 (26% O2-balance He), one with and one without added dead space. EFL was defined by the proximity of the tidal to the maximal flow-volume loop. With N2O2 during heavy and maximal exercise, 1) EFL was present in all six subjects during heavy [19 +/- 2% of tidal volume (VT) intersected the maximal flow-volume loop] and maximal exercise (43 +/- 8% of VT), 2) the slopes of the ventilation (DeltaVE) and peak esophageal pressure responses to added dead space (e.g., DeltaVE/DeltaPETCO2, where PETCO2 is end-tidal PCO2) were reduced relative to submaximal exercise, 3) end-expiratory lung volume (EELV) increased and end-inspiratory lung volume reached a plateau at 88-91% of total lung capacity, and 4) VT reached a plateau and then fell as work rate increased. With HeO2 (compared with N2O2) breathing during heavy and maximal exercise, 1) HeO2 increased maximal flow rates (from 20 to 38%) throughout the range of vital capacity, which reduced EFL in all subjects during tidal breathing, 2) the gains of the ventilatory and inspiratory esophageal pressure responses to added dead space increased over those during room air breathing and were similar at all exercise intensities, 3) EELV was lower and end-inspiratory lung volume remained near 90% of total lung capacity, and 4) VT was increased relative to room air breathing. We conclude that EFL or even impending EFL during heavy and maximal exercise and with added dead space in fit subjects causes EELV to increase, reduces the VT, and constrains the increase in respiratory motor output and ventilation.

Effects of prior exercise on exercise-induced arterial hypoxemia in young women.

Twenty-eight healthy women (ages 27.2 +/- 6.4 yr) with widely varying fitness levels [maximal O2 consumption (VO2 max), 31-70 ml . kg-1 . min-1] first completed a progressive incremental treadmill test to VO2 max (total duration, 13.3 +/- 1.4 min; 97 +/- 37 s at maximal workload), rested for 20 min, and then completed a constant-load treadmill test at maximal workload (total duration, 143 +/- 31 s). At the termination of the progressive test, 6 subjects had maintained arterial PO2 (PaO2) near resting levels, whereas 22 subjects showed a >10 Torr decrease in PaO2 [78.0 +/- 7.2 Torr, arterial O2 saturation (SaO2), 91.6 +/- 2.4%], and alveolar-arterial O2 difference (A-aDO2, 39.2 +/- 7.4 Torr). During the subsequent constant-load test, all subjects, regardless of their degree of exercise-induced arterial hypoxemia (EIAH) during the progressive test, showed a nearly identical effect of a narrowed A-aDO2 (-4.8 +/- 3.8 Torr) and an increase in PaO2 (+5.9 +/- 4.3 Torr) and SaO2 (+1.6 +/- 1.7%) compared with at the end point of the progressive test. Therefore, EIAH during maximal exercise was lessened, not enhanced, by prior exercise, consistent with the hypothesis that EIAH is not caused by a mechanism which persists after the initial exercise period and is aggravated by subsequent exercise, as might be expected of exercise-induced structural alterations at the alveolar-capillary interface. Rather, these findings in habitually active young women point to a functionally based mechanism for EIAH that is present only during the exercise period.

Assessment of inspiratory flow limitation invasively and noninvasively during sleep.

To define the standard of airway flow limitation, pharyngeal pressure and flow rate were measured during wakefulness and sleep in seven habitual snorers with widely varying degrees of sleep-induced increases in upper airway resistance. Inspiratory pressure:flow relationships were used to group breaths into four categories of flow limitation, including linear (Level 1), mildly alinear (Level 2), constant flow rate with no pressure dependence (Level 3), and decreasing flow rate throughout significant portions of inspiration, i.e., negative pressure dependence (Level 4). These pressure:flow rate gold standards of flow limitation were used to evaluate a flow limitation index derived from the time profile (or "shape") of three noninvasive estimates of flow rate: (1) pneumotach flow rate, (2) differentiated sum respiratory inductance plethysmography (RIP), and (3) nasal pressure. A nonflow limited template for each of these noninvasive measurements was taken from awake breaths and the difference in area determined between the template breath and each of the noninvasive signals measured during nonrapid eye movement (NREM) sleep. The noninvasive flow limitation indices were found to be effective in differentiating severe types of inspiratory flow limitation, i.e., Level 1 versus Level 3 or Level 4 (sensitivity/specificity > 80%). On the other hand, these indirect indices were not able to consistently detect mild levels of flow limitation (Level 1 versus Level 2; sensitivity/specificity = 62 to 72%); nor were these noninvasive estimates of flow rate "shape" sensitive to breaths with a high but fixed resistance throughout inspiration. The area index derived from measurements of pressure at the nares (Pn) was the most sensitive, nonperturbing, noninvasive measure of flow rate and flow limitation, and we recommend its use for recognizing most of the common types of moderate to severe levels of airway flow limitation in sleeping subjects.

Effects of respiratory muscle work on cardiac output and its distribution during maximal exercise.

We have recently demonstrated that changes in the work of breathing during maximal exercise affect leg blood flow and leg vascular conductance (C. A. Harms, M. A. Babcock, S. R. McClaran, D. F. Pegelow, G. A. Nickele, W. B. Nelson, and J. A. Dempsey. J. Appl. Physiol. 82: 1573-1583, 1997). Our present study examined the effects of changes in the work of breathing on cardiac output (CO) during maximal exercise. Eight male cyclists [maximal O2 consumption (VO2 max): 62 +/- 5 ml . kg-1 . min-1] performed repeated 2.5-min bouts of cycle exercise at VO2 max. Inspiratory muscle work was either 1) at control levels [inspiratory esophageal pressure (Pes): -27.8 +/- 0.6 cmH2O], 2) reduced via a proportional-assist ventilator (Pes: -16.3 +/- 0.5 cmH2O), or 3) increased via resistive loads (Pes: -35.6 +/- 0.8 cmH2O). O2 contents measured in arterial and mixed venous blood were used to calculate CO via the direct Fick method. Stroke volume, CO, and pulmonary O2 consumption (VO2) were not different (P > 0.05) between control and loaded trials at VO2 max but were lower (-8, -9, and -7%, respectively) than control with inspiratory muscle unloading at VO2 max. The arterial-mixed venous O2 difference was unchanged with unloading or loading. We combined these findings with our recent study to show that the respiratory muscle work normally expended during maximal exercise has two significant effects on the cardiovascular system: 1) up to 14-16% of the CO is directed to the respiratory muscles; and 2) local reflex vasoconstriction significantly compromises blood flow to leg locomotor muscles.

Smaller lungs in women affect exercise hyperpnea.

We subjected 29 healthy young women (age: 27 +/- 1 yr) with a wide range of fitness levels [maximal oxygen uptake (VO2 max): 57 +/- 6 ml . kg-1 . min-1; 35-70 ml . kg-1 . min-1] to a progressive treadmill running test. Our subjects had significantly smaller lung volumes and lower maximal expiratory flow rates, irrespective of fitness level, compared with predicted values for age- and height-matched men. The higher maximal workload in highly fit (VO2 max > 57 ml . kg-1 . min-1, n = 14) vs. less-fit (VO2 max < 56 ml . kg-1 . min-1, n = 15) women caused a higher maximal ventilation (VE) with increased tidal volume (VT) and breathing frequency (fb) at comparable maximal VT/vital capacity (VC). More expiratory flow limitation (EFL; 22 +/- 4% of VT) was also observed during heavy exercise in highly fit vs. less-fit women, causing higher end-expiratory and end-inspiratory lung volumes and greater usage of their maximum available ventilatory reserves. HeO2 (79% He-21% O2) vs. room air exercise trials were compared (with screens added to equalize external apparatus resistance). HeO2 increased maximal expiratory flow rates (20-38%) throughout the range of VC, which significantly reduced EFL during heavy exercise. When EFL was reduced with HeO2, VT, fb, and VE (+16 +/- 2 l/min) were significantly increased during maximal exercise. However, in the absence of EFL (during room air exercise), HeO2 had no effect on VE. We conclude that smaller lung volumes and maximal flow rates for women in general, and especially highly fit women, caused increased prevalence of EFL during heavy exercise, a relative hyperinflation, an increased reliance on fb, and a greater encroachment on the ventilatory "reserve." Consequently, VT and VE are mechanically constrained during maximal exercise in many fit women because the demand for high expiratory flow rates encroaches on the airways' maximum flow-volume envelope.

High frequency diaphragmatic fatigue detected with paired stimuli in humans.

PURPOSE: The purpose of this study was to determine whether high frequency fatigue was present in the diaphragm after intense whole body endurance exercise. METHODS: We used bilateral phrenic nerve stimulation (BPNS) before and during recovery from whole body exercise to detect fatigue in the diaphragm. To detect high frequency fatigue we used paired stimuli at 10, 20, 50, 70, and 100 Hz frequency and determined the transdiaphragmatic pressure (Pdi) response to the second stimulation (T2). RESULTS: The subjects (N = 10) exercised at 93.3 +/- 2.3% of their VO2max for 9.9 +/- 0.5 min. The Pdi response to "twitch" and 10 Hz "tetanic" stimulation was decreased immediately after exercise versus pre-exercise values (-23.4 +/- 3.3%). The T2 amplitude was substantially reduced at all frequencies immediately after exercise (-28.0%), but by 30 min into recovery the T2 amplitude at 70 and 100 Hz was not different from pre-exercise values. In contrast, at 10 and 20 Hz the T2 response was still significantly reduced. CONCLUSIONS: We interpret these data to mean that high frequency fatigue as well as low frequency fatigue were present in the diaphragm after intense whole body endurance exercise.

Exercise-induced arterial hypoxaemia in healthy young women.

1. We questioned whether exercise-induced arterial hypoxaemia (EIAH) occurs in healthy active women, who have smaller lungs, reduced lung diffusion, and lower maximal O2 consumption rate (VO2,max) than age- and height-matched men. 2. Twenty-nine healthy young women with widely varying fitness levels (VO2,max, 57 +/- 6 ml kg-1 min-1; range, 35-70 ml kg-1 min-1; or 148 +/- 5%; range, 93-188% predicted) and normal resting lung function underwent an incremental treadmill test to VO2,max during the follicular phase of their menstrual cycle. Arterial blood samples were taken at rest and near the end of each workload. 3. Arterial PO2 (Pa,O2) decreased > 10 mmHg below rest in twenty-two of twenty-nine subjects at VO2,max (Pa,O2, 77.5 +/- 0.9 mmHg; range, 67-88 mmHg; arterial O2 saturation (Sa,O2), 92.3 +/- 0.2%; range, 87-94%). The remaining seven subjects maintained Pa,O2 within 10 mmHg of rest. Pa,O2 at VO2,max was inversely related to the alveolar to arterial O2 difference (A-aDO2) (r = -0.93; 35-52 mmHg) and to arterial PCO2 (Pa,CO2) (r = -0.62; 26-39 mmHg). 4. EIAH was inversely related to VO2,max (r = -0.49); however, there were many exceptions. Almost half of the women with significant EIAH had VO2,max within 15% of predicted normal values (VO2,max, 40-55 ml kg-1 min-1); among subjects with very high VO2,max (55-70 ml kg-1 min-1), the degree of excessive A-aDO2 and EIAH varied markedly (e.g. A-aDO2, 30-50 mmHg; Pa,O2, 68-91 mmHg). 5. In the women with EIAH at VO2,max, many began to experience an excessive widening of their A-aDO2 during moderate intensity exercise, which when combined with a weak ventilatory response, led to a progressive hypoxaemia. Inactive, less fit subjects had no EIAH and narrower A-aDO2 when compared with active, fitter subjects at the same VO2 (40-50 ml kg-1 min-1). 6. These data demonstrate that many active healthy young women experience significant EIAH, and at a VO2,max that is substantially less than those in their active male contemporaries. The onset of EIAH during submaximal exercise, and/or its occurrence at a relatively low VO2,max, implies that lung structure/function subserving alveolar to arterial O2 transport is abnormally compromised in many of these habitually active subjects.

Blood pressure perturbations caused by subclinical sleep-disordered breathing.

We studied the acute effects of apneas and hypopneas on blood pressure in a nonclinic population of middle-aged adults. Arterial pressure was measured noninvasively (photoelectric plethysmography) during an overnight, in-laboratory polysomnographic study in 72 men and 23 women enrolled in the Wisconsin Sleep Cohort Study, a population-based study of sleep-disordered breathing. Sleep-disordered breathing events (272 apneas and 1469 hypopneas) were observed in 92% of subjects. The across-subject mean decreases in arterial O2 saturation were 9+/-8% (SD) for apneas (17+/-8 seconds duration) and 4+/-3% for hypopneas (21+/-6 seconds duration; 41+/-17% of baseline ventilation). In both apneas and hypopneas, even those with only 1% to 3% O2 desaturations, blood pressure decreased during the event, followed by an abrupt increase in the postevent recovery period. Mean values for peak changes in blood pressure (difference between the maximum during the recovery period and the minimum during the event) were 23+/-10 mm Hg for systolic and 13+/-6 mm Hg for diastolic pressure. The strongest predictors of the pressor responses to apneas and hypopneas were (in order of importance): magnitude of the ventilatory overshoot, length of the event, magnitude of changes in heart rate and arterial O2 saturation, and presence or absence of electroencephalographic arousal. We speculate that these fluctuations may play a role in the pathogenesis of hypertension in individuals with subclinical sleep-disordered breathing.

Respiratory muscle work compromises leg blood flow during maximal exercise.

We hypothesized that during exercise at maximal O2 consumption (VO2max), high demand for respiratory muscle blood flow (Q) would elicit locomotor muscle vasoconstriction and compromise limb Q. Seven male cyclists (VO2max 64 +/- 6 ml.kg-1.min-1) each completed 14 exercise bouts of 2.5-min duration at VO2max on a cycle ergometer during two testing sessions. Inspiratory muscle work was either 1) reduced via a proportional-assist ventilator, 2) increased via graded resistive loads, or 3) was not manipulated (control). Arterial (brachial) and venous (femoral) blood samples, arterial blood pressure, leg Q (Qlegs; thermodilution), esophageal pressure, and O2 consumption (VO2) were measured. Within each subject and across all subjects, at constant maximal work rate, significant correlations existed (r = 0.74-0.90; P < 0.05) between work of breathing (Wb) and Qlegs (inverse), leg vascular resistance (LVR), and leg VO2 (VO2legs; inverse), and between LVR and norepinephrine spillover. Mean arterial pressure did not change with changes in Wb nor did tidal volume or minute ventilation. For a +/-50% change from control in Wb, Qlegs changed 2 l/min or 11% of control, LVR changed 13% of control, and O2 extraction did not change; thus VO2legs changed 0.4 l/min or 10% of control. Total VO2max was unchanged with loading but fell 9.3% with unloading; thus VO2legs as a percentage of total VO2max was 81% in control, increased to 89% with respiratory muscle unloading, and decreased to 71% with respiratory muscle loading. We conclude that Wb normally incurred during maximal exercise causes vasoconstriction in locomotor muscles and compromises locomotor muscle perfusion and VO2.

Aerobic fitness effects on exercise-induced low-frequency diaphragm fatigue.

We used bilateral phrenic nerve stimulation (BPNS; at 1, 10, and 20 Hz at functional residual capacity) to compare the amount of exercise-induced diaphragm fatigue between two groups of healthy subjects, a high-fit group [maximal O2 consumption (VO2max) = 69.0 +/- 1.8 ml.kg-1.min-1, n = 11] and a fit group (VO2max = 50.4 +/- 1.7 ml.kg-1.min-1, n = 13). Both groups exercised at 88-92% VO2max for about the same duration (15.2 +/- 1.7 and 17.9 +/- 2.6 min for high-fit and fit subjects, respectively, P > 0.05). The supramaximal BPNS test showed a significant reduction (P < 0.01) in the BPNS transdiaphragmatic pressure (Pdi) immediately after exercise of -23.1 +/- 3.1% for the high-fit group and -23.1 +/- 3.8% (P > 0.05) for the fit group. Recovery of the BPNS Pdi took 60 min in both groups. The high-fit group exercised at a higher absolute workload, which resulted in a higher CO2 production (+26%), a greater ventilatory demand (+16%) throughout the exercise, and an increased diaphragm force output (+28%) over the initial 60% of the exercise period. Thereafter, diaphragm force output declined, despite a rising minute ventilation, and it was not different between most of the high-fit and fit subjects. In summary, the high-fit subjects showed diaphragm fatigue as a result of heavy endurance exercise but were also partially protected from excessive fatigue, despite high ventilatory requirements, because their hyperventilatory response to endurance exercise was reduced, their diaphragm was utilized less in providing the total ventilatory response, and possibly their diaphragm aerobic capacity was greater.