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Biomedical subjects

J A Dempsey

Publications and source records attributed to J A Dempsey.

At least 37 records · Page 2Linked to original sources
PubMed1999

Non-chemical inhibition of respiratory motor output during mechanical ventilation in sleeping humans.

1. To determine the magnitude and time course of changes in respiratory motor output caused by non-chemical influences, six sleeping subjects underwent assist-control mechanical ventilation (ACMV) at increased tidal volume (VT). During ACMV, end-tidal PCO2 (PET,CO2) was either held at normocapnic levels (PET,CO2, 0.6-1.1 mmHg > control) by adding CO2 to the inspirate, or it was allowed to fall (hypocapnia). 2. Each sleeping subject underwent several repeat trials of twenty-five ACMV breaths (VT, 1.3 or 2.1 times control; peak flow rate, 30-40 l min-1; inspiratory time, +/- 0.3 s of control). The end-tidal to arterial PCO2 difference throughout normocapnic ACMV at raised VT was unchanged from eupnoeic levels during studies in wakefulness. 3. Normocapnic ACMV at both the smaller and larger increases in VT decreased the amplitude of respiratory motor output, as judged by decreased maximum rate of rise of mask pressure (Pm) (mean dPm/dtmax, 46-68% of control), reduced diaphragmatic EMG (to 55% of control) and reduced VT on the first spontaneous breath after ACMV (to 70% of control). Expiratory time (TE) was slightly prolonged (13-32% > control). This inhibition of amplitude of respiratory motor output progressed over the first five to seven ventilator cycles, was maintained over the remaining 18-20 cycles and persisted for three to five spontaneous breaths immediately following cessation of ACMV. 4. Hypocapnia did not further inhibit respiratory motor output amplitude beyond the effect of normocapnic ACMV at high VT, but did cause highly variable prolongation of TE when PET,CO2 was reduced by greater than 3 mmHg for at least five ventilator cycles. 5. These data in sleeping humans support the existence of a significant, non-chemical inhibitory influence of ACMV at increased VT and positive pressure upon the amplitude of respiratory motor output; this effect is manifested both during and following normocapnic mechanical ventilation.

Adult↗
PubMed1999

Inhibition of inspiratory motor output by high-frequency low-pressure oscillations in the upper airway of sleeping dogs.

1. We utilized a chronically tracheostomized, unanaesthetized dog model to study the reflex effects on inspiratory motor output of low-amplitude, high-frequency pressure oscillations (HFPOs) applied to the isolated upper airway (UA) during stable non-rapid eye movement (NREM) sleep. 2. HFPOs (30 Hz and +/-2 to +/-4 cmH2O) were applied via a piston pump during eupnoea, inspiratory resistive loading and tracheal occlusion. 3. When applied to the patent UA during expiration, and especially during late expiration, HFPOs prolonged expiratory time (TE) and tonically activated the genioglossus muscle EMG. When applied to the patent UA during inspiration, HFPOs caused tonic activation of the genioglossus muscle EMG and inhibition of inspiratory motor output by either: (a) a shortening of inspiratory time (TI), as inspiration was terminated coincident with the onset of HFPOs; or (b) a prolonged TI accompanied by a decreased rate of rise of diaphragm EMG and rate of fall of tracheal pressure. These effects of HFPOs were observed during eupnoea and inspiratory resistive loading, but were maximal during tracheal occlusion where the additional inhibitory effects of lung inflation reflexes were minimized. 4. During eupnoea, topical anaesthesia of the UA abolished the HFPO-induced prolongation of TE, suggesting that the response was mediated primarily by mechanoreceptors close to the mucosal surface; whereas the TE-prolonging effects of a sustained square wave of negative pressure (range, -4.0 to -14.9 cmH2O) sufficient to close the airway were preserved following anaesthesia. 5. These results demonstrate that high-frequency, low-amplitude oscillatory pressure waves in the UA, similar to those found in snoring, produce reflex inhibition of inspiratory motor output. This reflex may help maintain UA patency by decreasing the collapsing pressure generated by the inspiratory pump muscles and transmitted to the UA.

Afferent Pathways↗
PubMed1999

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.

Adult↗
PubMed1999

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).

Adult↗
PubMed1999

Exercise-induced arterial hypoxemia.

Exercise-induced arterial hypoxemia (EIAH) at or near sea level is now recognized to occur in a significant number of fit, healthy subjects of both genders and of varying ages. Our review aims to define EIAH and to critically analyze what we currently understand, and do not understand, about its underlying mechanisms and its consequences to exercise performance. Based on the effects on maximal O(2) uptake of preventing EIAH, we suggest that mild EIAH be defined as an arterial O(2) saturation of 93-95% (or 3-4% 25-30 Torr) and inadequate compensatory hyperventilation (arterial PCO(2) >35 Torr) commonly contribute to EIAH, as do acid- and temperature-induced shifts in O(2) dissociation at any given arterial PO(2). In turn, expiratory flow limitation presents a significant mechanical constraint to exercise hyperpnea, whereas ventilation-perfusion ratio maldistribution and diffusion limitation contribute about equally to the excessive A-a DO(2). Exactly how diffusion limitation is incurred or how ventilation-perfusion ratio becomes maldistributed with heavy exercise remains unknown and controversial. Hypotheses linked to extravascular lung water accumulation or inflammatory changes in the "silent" zone of the lung's peripheral airways are in the early stages of exploration. Indirect evidence suggests that an inadequate hyperventilatory response is attributable to feedback inhibition triggered by mechanical constraints and/or reduced sensitivity to existing stimuli; but these mechanisms cannot be verified without a sensitive measure of central neural respiratory motor output. Finally, EIAH has detrimental effects on maximal O(2) uptake, but we have not yet determined the cause or even precisely identified which organ system, involved directly or indirectly with O(2) transport to muscle, is responsible for this limitation.

Animals↗
PubMed1999

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).

Adult↗
PubMed1999

Biological activity of the multitargeted antifolate, MTA (LY231514), in human cell lines with different resistance mechanisms to antifolate drugs.

Prior studies have indicated that MTA requires intracellular polyglutamation for optimal cytotoxic effect and that these polyglutamates potently inhibit several key enzymes of folate metabolism, including thymidylate synthase (TS), dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase (GARFT). In the present studies, we have investigated the mechanistic basis for resistance to MTA in several human tumor cell lines. The cell lines were developed for resistance by the gradual exposure to stepwise (fivefold) increases in the concentration of MTA over a 5-month period. The degree of resistance was 140-fold for GC3 colon carcinoma, 117-fold for HCT-8 ileocecal carcinoma, and 729-fold for CCRF-CEM leukemia cells adapted to 2 micromol/L MTA. The lines had strong cross-resistance (>3,200-fold) to raltitrexed. Only modest resistance was noted for methotrexate and the GARFT inhibitor, LY309887. The cytotoxicity of MTA in wild-type cells was only partially alleviated by thymidine addition (5 micromol/L) and complete protection required the addition of both hypoxanthine (100 micromol/L) and thymidine. In contrast, thymidine alone totally lacked protective activity in the MTA-resistant lines. The cells either demonstrated a GARFT-like reversal pattern (complete protection by hypoxanthine) for GC3MTA or a dihydrofolate reductase-like reversal pattern (complete protection by the combination of hypoxanthine and thymidine) for HCT-8MTA and CCRF-CEM(MTA) cells. Cellular resistance was multifactorial and stable on removal of selective pressure. Only GC3MTA cells showed increased TS activity (approximately 40-fold). Accumulations of 3H-MTA at 24 hours in CCRF-CEM(MTA), HCT-8MTA, and GC3MTA cells were 2%, 6%, and 46% of wild-type values, respectively. We also evaluated the cytotoxic activity of MTA in MCF-7 breast carcinoma and H630 colon carcinoma cells selected for resistance to raltitrexed and 5-fluorouracil, respectively, via TS amplification (provided by Dr P.G. Johnston, Belfast, Ireland). These cells demonstrated more than 200-fold less resistance to MTA compared with raltitrexed and MTA-induced cytotoxicity was prevented by hypoxanthine. These studies suggest that in addition to TS modulation, secondary targets emerge during the development of MTA resistance.

Antimetabolites, Antineoplastic↗
PubMed1999

Cardiovascular consequences of exercise hyperpnea.

In summary, evidence shows that the respiratory muscles demand a significant portion of the cardiac output during maximal exercise. Estimates of both animal and human blood flow and VO2 to the respiratory muscles during maximal exercise approximate 14-16% of the total cardiac output and VO2. During heavy exercise, this metabolic demand of the respiratory muscles affects the distribution of cardiac output between the respiratory muscles and the legs such that leg vascular conductance and blood flow increases with respiratory muscle unloading and decreases with respiratory loading. The reflex effects underlying this blood flow redistribution remain unknown; however, these data do clearly support the existence of a significant sympathetic effect output to working skeletal muscle in heavy exercise. These data also invite the exciting (although speculative) prospect of important chemo- or mechano-induced reflexes emanating from respiratory muscle under load.Finally, while not yet completely understood or investigated, it appears that respiratory muscle work during strenuous exercise affects exercise performance.

Animals↗
PubMed1998

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.

Cohort Studies↗
PubMed1998

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.

Adolescent↗
PubMed1998

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.

Adult↗
PubMed1998

An induced blood pressure rise does not alter upper airway resistance in sleeping humans.

Sleep apnea is associated with episodic increases in systemic blood pressure. We investigated whether transient increases in arterial pressure altered upper airway resistance and/or breathing pattern in nine sleeping humans (snorers and nonsnorers). A pressure-tipped catheter was placed below the base of the tongue, and flow was measured from a nose or face mask. During non-rapid-eye-movement sleep, we injected 40- to 200-microgram i.v. boluses of phenylephrine. Parasympathetic blockade was used if bradycardia was excessive. Mean arterial pressure (MAP) rose by 20 +/- 5 (mean +/- SD) mmHg (range 12-37 mmHg) within 12 s and remained elevated for 105 s. There were no significant changes in inspiratory or expiratory pharyngeal resistance (measured at peak flow, peak pressure, 0.2 l/s or by evaluating the dynamic pressure-flow relationship). At peak MAP, end-tidal CO2 pressure fell by 1.5 Torr and remained low for 20-25 s. At 26 s after peak MAP, tidal volume fell by 19%, consistent with hypocapnic ventilatory inhibition. We conclude that transient increases in MAP of a magnitude commonly observed during non-rapid-eye-movement sleep-disordered breathing do not increase upper airway resistance and, therefore, will not perpetuate subsequent obstructive events.

Adrenergic alpha-Agonists↗
PubMed1998

Effect of upper airway negative pressure on inspiratory drive during sleep.

To determine the effect of upper airway (UA) negative pressure and collapse during inspiration on regulation of breathing, we studied four unanesthetized female dogs during wakefulness and sleep while they breathed via a fenestrated tracheostomy tube, which was sealed around the permanent tracheal stoma. The snout was sealed with an airtight mask, thereby isolating the UA when the fenestration (Fen) was closed and exposing the UA to intrathoracic pressure changes, but not to flow changes, when Fen was open. During tracheal occlusion with Fen closed, inspiratory time (TI) increased during wakefulness, non-rapid-eye-movement (NREM) sleep and rapid-eye-movement (REM) sleep (155 +/- 8, 164 +/- 11, and 161 +/- 32%, respectively), reflecting the removal of inhibitory lung inflation reflexes. During tracheal occlusion with Fen open (vs. Fen closed): 1) the UA remained patent; 2) TI further increased during wakefulness and NREM (215 +/- 52 and 197 +/- 28%, respectively) but nonsignificantly during REM sleep (196 +/- 42%); 3) mean rate of rise of diaphragm EMG (EMGdi/TI) and rate of fall of tracheal pressure (Ptr/TI) were decreased, reflecting an additional inhibitory input from UA receptors; and 4) both EMGdi/TI and Ptr/TI were decreased proportionately more as inspiration proceeded, suggesting greater reflex inhibition later in the effort. Similar inhibitory effects of exposing the UA to negative pressure (via an open tracheal Fen) were seen when an inspiratory resistive load was applied over several breaths during wakefulness and sleep. These inhibitory effects persisted even in the face of rising chemical stimuli. This inhibition of inspiratory motor output is alinear within an inspiration and reflects the activation of UA pressure-sensitive receptors by UA distortion, with greater distortion possibly occurring later in the effort.

Air Pressure↗
PubMed1998

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.

Adolescent↗
PubMed1998

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.

Adult↗
PubMed1998

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.

Adolescent↗
PubMed1998

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.

Adult↗