Acceleration of VO2 kinetics in heavy submaximal exercise by hyperoxia and prior high-intensity exercise

MacDonald, Maureen, Preben K. Pedersen, and Richard L. Hughson. Acceleration ofO₂ kinetics in heavysubmaximal exercise by hyperoxia and prior high-intensity exercise.J. Appl. Physiol. 83(4):1318-1325, 1997.We examined the hypothesis thatO₂ uptake (O₂) wouldchange more rapidly at the onset of step work rate transitions inexercise with hyperoxic gas breathing and after prior high-intensityexercise. The kinetics ofO₂ were determined from themean response time (MRT; time to 63% of total change inO₂) andcalculations of O₂ deficit andslow component during normoxic and hyperoxic gas breathing in one groupof seven subjects during exercise below and above ventilatory threshold(VT) and in another group of seven subjects during exercise above VTwith and without prior high-intensity exercise. In exercise transitions below VT, hyperoxic gas breathing did not affect the kinetic response of O₂ at theonset or end of exercise. At work rates above VT, hyperoxic gasbreathing accelerated both the on- and off-transient MRT, reduced theO₂ deficit, and decreased theO₂ slow component fromminute 3 to minute6 of exercise, compared with normoxia. Prior exerciseabove VT accelerated the on-transient MRT and reduced theO₂ slow component fromminute 3 to minute6 of exercise in a second bout of exercise with bothnormoxic and hyperoxic gas breathing. However, the summatedO₂ deficit in the second normoxicand hyperoxic steps was not different from that of the first steps inthe same gas condition. Faster on-transient responses in exerciseabove, but not below, VT with hyperoxia and, to a lesser degree, afterprior high-intensity exercise above VT support the theory of anO₂ transport limitation at theonset of exercise for workloads >VT.

     

Muscle capillarization, O2 diffusion distance, and VO2 kinetics in old and young individuals

Chilibeck, P. D., D. H. Paterson, D. A. Cunningham, A. W. Taylor, and E. G. Noble. Muscle capillarization,O₂ diffusion distance, andO₂ kinetics in old andyoung individuals. J. Appl. Physiol.82(1): 63-69, 1997.The relationships between muscle capillarization, estimated O₂diffusion distance from capillary to mitochondria, andO₂ uptake(O₂) kineticswere studied in 11 young (mean age, 25.9 yr) and 9 old (mean age, 66.0 yr) adults. O₂kinetics were determined by calculating the time constants () forthe phase 2 O₂ adjustment to andrecovery from the average of 12 repeats of a 6-min, moderate-intensityplantar flexion exercise. Muscle capillarization was determined fromcross sections of biopsy material taken from lateral gastrocnemius.Young and old groups had similarO₂ kinetics(O₂-on = 44 vs. 48 s;O₂-off = 33 vs. 44 s, for young and old, respectively), muscle capillarization, andestimated O₂ diffusion distances.Muscle capillarization, expressed as capillary density or averagenumber of capillary contacts per fiber/average fiber area, and theestimates of diffusion distance were significantly correlated toO₂-off kinetics in theyoung (r = 0.68 to 0.83;P < 0.05). We conclude that1) capillarization andO₂ kinetics during exerciseof a muscle group accustomed to everyday activity (e.g., walking) arewell maintained in old individuals, and2) in the young, recovery of O₂ after exercise isfaster, with a greater capillary supply over a given muscle fiber areaor shorter O₂ diffusion distances.

     

The VO2 slow component for severe exercise depends on type of exercise and is not correlated with time to fatigue

The purpose ofthis study was to examine the influence of the type of exercise(running vs. cycling) on the O₂uptake (O₂) slow component.Ten triathletes performed exhaustive exercise on a treadmill and on acycloergometer at a work rate corresponding to 90% of maximalO₂ (90% work rate maximalO₂). The duration of thetests before exhaustion was superimposable for both type of exercises(10 min 37 s ± 4 min 11 s vs. 10 min 54 s ± 4 min 47 s forrunning and cycling, respectively). TheO₂ slow component (difference between O₂ atthe last minute and minute 3 ofexercise) was significantly lower during running compared with cycling(20.9 ± 2 vs. 268.8 ± 24 ml/min). Consequently, there was norelationship between the magnitude of theO₂ slow component and thetime to fatigue. Finally, because blood lactate levels at the end of the tests were similar for both running (7.2 ± 1.9 mmol/l) and cycling (7.3 ± 2.4 mmol/l), there was a clear dissociation between blood lactate and the O₂slow component during running. These data demonstrate that1) theO₂ slow component dependson the type of exercise in a group of triathletes and2) the time to fatigue isindependent of the magnitude of theO₂ slow component and bloodlactate concentration. It is speculated that the difference in muscularcontraction regimen between running and cycling could account for thedifference in theO₂ slow component.

     

Respiratory muscle work compromises leg blood flow during maximal exercise

Harms, Craig A., Mark A. Babcock, Steven R. McClaran, DavidF. Pegelow, Glenn A. Nickele, William B. Nelson, and Jerome A. Dempsey.Respiratory muscle work compromises leg blood flow during maximalexercise. J. Appl. Physiol.82(5): 1573-1583, 1997.We hypothesized that duringexercise at maximal O₂ consumption (O_{2 max}),high demand for respiratory muscle blood flow() would elicit locomotor muscle vasoconstrictionand compromise limb . Seven male cyclists(O_{2 max} 64 ± 6 ml · kg¹ · min¹)each completed 14 exercise bouts of 2.5-min duration atO_{2 max} on a cycleergometer during two testing sessions. Inspiratory muscle work waseither 1) reduced via aproportional-assist ventilator, 2)increased via graded resistive loads, or3) was not manipulated (control).Arterial (brachial) and venous (femoral) blood samples, arterial bloodpressure, leg (legs;thermodilution), esophageal pressure, andO₂ consumption(O₂) weremeasured. Within each subject and across all subjects, at constantmaximal work rate, significant correlations existed(r = 0.74-0.90;P < 0.05) between work of breathing(Wb) and legs (inverse), leg vascular resistance (LVR), and leg O₂(O_{2 legs};inverse), and between LVR and norepinephrine spillover. Mean arterialpressure did not change with changes in Wb nor did tidal volume orminute ventilation. For a ±50% change from control in Wb,legs changed 2 l/min or 11% of control, LVRchanged 13% of control, and O₂extraction did not change; thusO_{2 legs}changed 0.4 l/min or 10% of control. TotalO_{2 max} was unchangedwith loading but fell 9.3% with unloading; thusO_{2 legs}as a percentage of totalO_{2 max} was 81% incontrol, increased to 89% with respiratory muscle unloading, anddecreased to 71% with respiratory muscle loading. We conclude that Wbnormally incurred during maximal exercise causes vasoconstriction inlocomotor muscles and compromises locomotor muscle perfusion andO₂.

     

Combined heart rate and activity improve estimates of oxygen consumption and carbon dioxide production rates

Moon, Jon K., and Nancy F. Butte. Combined heart rateand activity improve estimates of oxygen consumption and carbon dioxideproduction rates. J. Appl. Physiol.81(4): 1754-1761, 1996.Oxygen consumption(O₂) andcarbon dioxide production (CO₂) rates were measuredby electronically recording heart rate (HR) and physical activity (PA).Mean daily O₂ andCO₂ measurements by HR andPA were validated in adults (n = 10 women and 10 men) with room calorimeters. Thirteen linear and nonlinear functions of HR alone and HR combined with PA were tested as models of24-h O₂ andCO₂. Mean sleepO₂ andCO₂ were similar to basalmetabolic rates and were accurately estimated from HR alone[respective mean errors were 0.2 ± 0.8 (SD) and0.4 ± 0.6%]. The range of prediction errorsfor 24-h O₂ andCO₂ was smallestfor a model that used PA to assign HR for each minute to separateactive and inactive curves(O₂, 3.3 ± 3.5%; CO₂, 4.6 ± 3%). There were no significant correlations betweenO₂ orCO₂ errors and subject age,weight, fat mass, ratio of daily to basal energy expenditure rate, orfitness. O₂,CO₂, and energy expenditurerecorded for 3 free-living days were 5.6 ± 0.9 ml ^· min^{1 ·} kg¹,4.7 ± 0.8 ml ^· min^{1 ·} kg¹,and 7.8 ± 1.6 kJ/min, respectively. Combined HR and PA measured 24-h O₂ andCO₂ with a precisionsimilar to alternative methods.

     

Influence of muscle fiber type and pedal frequency on oxygen uptake kinetics of heavy exercise

Barstow, Thomas J., Andrew M. Jones, Paul H. Nguyen, andRichard Casaburi. Influence of muscle fiber type and pedal frequency on oxygen uptake kinetics of heavy exercise.J. Appl. Physiol. 81(4):1642-1650, 1996.We tested the hypothesis that the amplitude ofthe additional slow component ofO₂ uptake(O₂) during heavy exerciseis correlated with the percentage of type II (fast-twitch) fibers inthe contracting muscles. Ten subjects performed transitions to a workrate calculated to require aO₂ equal to 50% betweenthe estimated lactate (Lac) threshold and maximalO₂ (50%).Nine subjects consented to a muscle biopsy of the vastus lateralis. Toenhance the influence of differences in fiber type among subjects,transitions were made while subjects were pedaling at 45, 60, 75, and90 rpm in different trials. Baseline O₂ was designed to besimilar at the different pedal rates by adjusting baseline work ratewhile the absolute increase in work rate above the baseline was thesame. The O₂ response after the onset of exercise was described by a three-exponential model. Therelative magnitude of the slow component at the end of 8-min exercisewas significantly negatively correlated with %type I fibers at everypedal rate (r = 0.64 to 0.83, P < 0.05-0.01). Furthermore,the gain of the fast component forO₂ (asml ^· min^{1 ·} W¹)was positively correlated with the %type I fibers across pedal rates(r = 0.69-0.83). Increase inpedal rate was associated with decreased relative stress of theexercise but did not affect the relationships between%fiber type and O₂parameters. The relative contribution of the slow component was alsosignificantly negatively correlated with maximalO₂(r = 0.65), whereas the gainfor the fast component was positively associated(r = 0.68-0.71 across rpm). Theamplitude of the slow component was significantly correlated with netend-exercise Lac at all four pedal rates(r = 0.64-0.84), but Lac was notcorrelated with %type I (P > 0.05).We conclude that fiber type distribution significantly affects both thefast and slow components ofO₂ during heavy exerciseand that fiber type and fitness may have both codependent andindependent influences on the metabolic and gas-exchange responses toheavy exercise.

     

Gas exchange and cardiovascular kinetics with different exercise protocols in heart transplant recipients

Grassi, Bruno, Claudio Marconi, Michael Meyer, Michel Rieu,and Paolo Cerretelli. Gas exchange and cardiovascular kinetics with different exercise protocols in heart transplant recipients. J. Appl. Physiol. 82(6): 1952-1962, 1997.Metabolicand cardiovascular adjustments to various submaximal exercises wereevaluated in 82 heart transplant recipients (HTR) and in 35 controlsubjects (C). HTR were tested 21.5 ± 25.3 (SD) mo (range1.0-137.1 mo) posttransplantation. Three protocols were used:protocol A consisted of 5 min of rectangular 50-W load repeatedtwice, 5 min apart [5 min rest, 5 min 50 W (Ex 1), 5 minrecovery, 5 min 50 W (Ex 2)]; protocol B consistedof 5 min of rectangular load at 25, 50, or 75 W; protocol Cconsisted of 15 min of rectangular load at 25 W. Breath-by-breathpulmonary ventilation (E),O₂ uptake (O₂),and CO₂ output(CO₂) were determined.During protocol A, beat-by-beat cardiacoutput () was estimated by impedance cardiography. The half times (t_1/2) of the on- andoff-kinetics of the variables were calculated. In all protocols,t_1/2 values forO₂ on-,E on-, andCO₂ on-kinetics were higher(i.e., the kinetics were slower) in HTR than in C, independently ofworkload and of the time posttransplantation. Also,t_1/2 on- was higher in HTRthan in C. In protocol A, no significant difference of t_1/2 O₂on- was observed in HTR between Ex 1 (48 ± 9 s) and Ex2 (46 ± 8 s), whereas t_1/2 on- was higher during Ex 1 (55 ± 24 s)than during Ex 2 (47 ± 15 s). In all protocols and for all variables, the t_1/2 off-values were higher in HTRthan in C. In protocol C, no differences of steady-stateE,O₂, andCO₂ were observed in bothgroups between 5, 10, and 15 min of exercise. We conclude that1) in HTR, a "priming" exercise, while effective inspeeding up the adjustment of convective O₂ flow to muscle fibers during a second on-transition, did not affect theO₂ on-kinetics, suggestingthat the slower O₂ on- inHTR was attributable to peripheral (muscular) factors; 2) thedissociation between on- andO₂ on-kinetics in HTRindicates that an inertia of muscle metabolic machinery is the mainfactor dictating theO₂ on-kinetics; and 3) theO₂ off-kinetics was slowerin HTR than in C, indicating a greater alactic O₂ deficitin HTR and, therefore, a sluggish muscleO₂ adjustment.

     

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 oxygenuptake (O_{2 max}): 57 ± 6 ml · kg¹ · min¹;35-70ml · kg¹ · min¹]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(O_{2 max} > 57 ml · kg¹ · min¹,n = 14) vs. less-fit(O_{2 max} < 56 ml · kg¹ · min¹,n = 15) women caused a higher maximalventilation (E) with increased tidal volume (VT)and breathing frequency (f_b) atcomparable maximal VT/vitalcapacity (VC). More expiratory flow limitation (EFL; 22 ± 4% ofVT) was also observed duringheavy exercise in highly fit vs. less-fit women, causing higherend-expiratory and end-inspiratory lung volumes and greater usage oftheir maximum available ventilatory reserves.HeO₂ (79% He-21%O₂) vs. room air exercise trialswere compared (with screens added to equalize external apparatusresistance). HeO₂ increasedmaximal expiratory flow rates (20-38%) throughout the range ofVC, which significantly reduced EFL during heavy exercise. When EFL wasreduced with HeO₂, VT,f_b, andE (+16 ± 2 l/min) weresignificantly increased during maximal exercise. However, in theabsence of EFL (during room air exercise),HeO₂ had no effect onE. We conclude that smaller lungvolumes and maximal flow rates for women in general, and especiallyhighly fit women, caused increased prevalence of EFL during heavyexercise, a relative hyperinflation, an increased reliance onf_b, and a greater encroachment onthe ventilatory "reserve." Consequently,VT andE are mechanically constrained duringmaximal exercise in many fit women because the demand for highexpiratory flow rates encroaches on the airways' maximum flow-volumeenvelope.

     

Abnormal oxygen uptake kinetic responses in women with type II diabetes mellitus

Persons with type II diabetes mellitus(DM), even without cardiovascular complications have a decreasedmaximal oxygen consumption (O_{2 max}) andsubmaximal oxygen consumption(O₂) duringgraded exercise compared with healthy controls. Weevaluated the hypothesis that change in the rate ofO₂ in response to the onsetof constant-load exercise (measured byO₂-uptakekinetics) was slowed in persons with type II DM. Ten premenopausalwomen with uncomplicated type II DM, 10 overweight, nondiabeticwomen, and 10 lean, nondiabetic women had aO_{2 max} test. On twoseparate occasions, subjects performed 7-min bouts of constant-loadbicycle exercise at workloads below and above the lactate threshold toenable measurements of O₂kinetics and heart rate kinetics (measuring rate of heart rate rise).O_{2 max}was reduced in subjects with type II DM compared with both lean andoverweight controls (P < 0.05).Subjects with type II DM had slowerO₂ and heart rate kineticsthan did controls at constant workloads below the lactate threshold.The data suggest a notable abnormality in the cardiopulmonary responseat the onset of exercise in people with type II DM. The findings mayreflect impaired cardiac responses to exercise, although an additional defect in skeletal muscle oxygen diffusion or mitochondrial oxygen utilization is also possible.

     

Nitric oxide response in exhaled air during an incremental exhaustive exercise

Chirpaz-Oddou, M. F., A. Favre-Juvin, P. Flore, J. Eterradossi, M. Delaire, F. Grimbert, and A. Therminarias. Nitric oxide response in exhaled air during an incremental exhaustive exercise. J. Appl. Physiol. 82(4):1311-1318, 1997.This study examines the response of the exhalednitric oxide (NO) concentration (CNO) and the exhaled NOoutput(NO)during incremental exercise and during recovery in six sedentary women,seven sedentary men, and eight trained men. The protocolconsisted of increasing the exercise intensity by 30 W every 3 minuntil exhaustion, followed by 5 min of recovery. Minute ventilation(E), oxygen consumption (O₂), carbon dioxideproduction, heart rate, CNO, andNOwere measured continuously. TheCNO in exhaled air decreasedsignificantly provided that the exercise intensity exceeded 65% of thepeak O₂. It reached similarvalues, at exhaustion, in all three groups. TheNO increasedproportionally with exercise intensity up to exhaustion and decreasedrapidly during recovery. At exhaustion, the mean values weresignificantly higher for trained men than for sedentary men andsedentary women. During exercise,NOcorrelates well with O₂,carbon dioxide production, E, and heartrate. For the same submaximal intensity, and thus a givenO₂ and probably a similarcardiac output,NO appearedto be similar in all three groups, even if theE was different. These results suggestthat, during exercise,NO is mainlyrelated to the magnitude of aerobic metabolism and that thisrelationship is not affected by gender differences or by noticeabledifferences in the level of physical training.

     

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

We have recently demonstrated that changes inthe work of breathing during maximal exercise affect leg blood flow andleg 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 changesin the work of breathing on cardiac output (CO) during maximalexercise. Eight male cyclists [maximalO₂ consumption(O_{2 max}):62 ± 5 ml · kg¹ · min¹]performed repeated 2.5-min bouts of cycle exercise atO_{2 max}. Inspiratorymuscle work was either 1) at controllevels [inspiratory esophageal pressure (Pes): 27.8 ± 0.6 cmH₂O],2) reduced via a proportional-assistventilator (Pes: 16.3 ± 0.5 cmH₂O), or 3) increased via resistive loads(Pes: 35.6 ± 0.8 cmH₂O).O₂ contents measured in arterialand mixed venous blood were used to calculate CO via the direct Fickmethod. Stroke volume, CO, and pulmonaryO₂ consumption(O₂) were not different(P > 0.05) between control andloaded trials atO_{2 max} but were lower(8, 9, and 7%, respectively) than control withinspiratory muscle unloading atO_{2 max}. Thearterial-mixed venous O₂difference was unchanged with unloading or loading. We combined thesefindings with our recent study to show that the respiratory muscle work normally expended during maximal exercise has two significant effectson the cardiovascular system: 1) upto 14-16% of the CO is directed to the respiratory muscles; and2) local reflex vasoconstriction significantly compromises blood flow to leg locomotor muscles.

     

Respiratory gas-exchange ratios during graded exercise in fed and fasted trained and untrained men

We evaluated the hypotheses that endurance training increasesrelative lipid oxidation over a wide range of relative exercise intensities in fed and fasted states and that carbohydrate nutrition causes carbohydrate-derived fuels to predominate as energy sources during exercise. Pulmonary respiratory gas-exchange ratios [(RER) = CO₂production/O₂ consumption(O₂)] were determinedduring four relative, graded exercise intensities in both fed andfasted states. Seven untrained (UT) men and seven category 2 and 3 US Cycling Federation cyclists (T) exercised in the morning in random order, with target power outputs of 20 and 40% peakO₂(O_{2 peak}) for 2 h,60% O_{2 peak} for 1.5 h, and 80%O_{2 peak} fora minimum of 30 min after either a 12-h overnight fast or 3 h after astandardized breakfast. Actual metabolic responses were 22 ± 0.33, 40 ± 0.31, 59 ± 0.32, and 75 ± 0.39%O_{2 peak}. T subjectsshowed significantly (P < 0.05)decreased RER compared with UT subjects at absolute workloads when fedand fasted. Fasting significantly decreased RER values compared withthe fed state at 22, 40, and 59%O_{2 peak} inT and at 40 and 59%O_{2 peak} in UTsubjects. Training decreased (P < 0.05) mean RER values compared with UT subjects at 22%O_{2 peak} when theyfasted, and at 40%O_{2 peak} when fed orfasted, but not at higher relative exercise intensities in eithernutritional state. Our results support the hypothesis that endurancetraining enhances lipid oxidation in men after a 12-h overnight fast at low relative exercise intensities (22 and 40%O_{2 peak}). However, atraining effect on RER was not apparent at high relative exercise intensities (59 and 75%O_{2 peak}). Becausemost athletes train and compete at exercise intensities >40% maximalO₂, they will not oxidize agreater proportion of lipids compared with untrained subjects,regardless of nutritional state.     

Human ventilatory response to 8h of euoxic hypercapnia

Tansley, John G., Michala E. F. Pedersen, Christine Clar,and Peter A. Robbins. Human ventilatory response to 8 h of euoxic hypercapnia. J. Appl.Physiol. 84(2): 431-434, 1998.Ventilation (E) risesthroughout 40 min of constant elevated end-tidalPCO₂ without reaching steady state(S. Khamnei and P. A. Robbins. Respir. Physiol. 81: 117-134, 1990). The present studyinvestigates 8 h of euoxic hypercapnia to determine whetherE reachessteady state within this time. Two protocols were employed:1) 8-h euoxic hypercapnia (end-tidalPCO₂ = 6.5 Torr above prestudy value,end-tidal PO₂ = 100 Torr) followed by 8-h poikilocapnic euoxia; and2) control, where the inspired gaswas air. Ewas measured over a 5-min period before the experiment and then hourly over a 16-h period. In the hypercapnia protocol,E had notreached a steady state by the first hour(P < 0.001, analysis of variance), but there were no further significant differences inEover hours 2-8 (analysis ofvariance). Efell promptly on return to eucapnic conditions. We conclude that,whereas there is a component of theE responseto hypercapnia that is slow, there is no progressive rise inE throughoutthe 8-h period.

     

Ventilatory response to exercise in diabetic subjects with autonomic neuropathy

Tantucci, C., P. Bottini, M. L. Dottorini, E. Puxeddu, G. Casucci, L. Scionti, and C. A. Sorbini. Ventilatory response toexercise in diabetic subjects with autonomic neuropathy.J. Appl. Physiol. 81(5):1978-1986, 1996.We have used diabetic autonomic neuropathy as amodel of chronic pulmonary denervation to study the ventilatoryresponse to incremental exercise in 20 diabetic subjects, 10 with(Dan+) and 10 without (Dan) autonomic dysfunction, and in 10 normal control subjects. Although both Dan+ and Dan subjectsachieved lower O₂ consumption andCO₂ production(CO₂) thancontrol subjects at peak of exercise, they attained similar values ofeither minute ventilation(E) oradjusted ventilation (E/maximalvoluntary ventilation). The increment of respiratory rate withincreasing adjusted ventilation was much higher in Dan+ than inDan and control subjects (P < 0.05). The slope of the linearE/CO₂relationship was 0.032 ± 0.002, 0.027 ± 0.001 (P < 0.05), and 0.025 ± 0.001 (P < 0.001) ml/min inDan+, Dan, and control subjects, respectively. Bothneuromuscular and ventilatory outputs in relation to increasingCO₂ were progressivelyhigher in Dan+ than in Dan and control subjects. At peak ofexercise, end-tidal PCO₂ was muchlower in Dan+ (35.9 ± 1.6 Torr) than in Dan (42.1 ± 1.7 Torr; P < 0.02) and control (42.1 ± 0.9 Torr; P < 0.005) subjects.We conclude that pulmonary autonomic denervation affects ventilatoryresponse to stressful exercise by excessively increasing respiratoryrate and alveolar ventilation. Reduced neural inhibitory modulationfrom sympathetic pulmonary afferents and/or increasedchemosensitivity may be responsible for the higher inspiratoryoutput.

     

O2 uptake kinetics after acetazolamide administration during moderate- and heavy-intensity exercise

Inhibition of carbonic anhydrase (CA) isassociated with a lower plasma lactate concentration([La]_pl)during fatiguing exercise. We hypothesized that a lower[La]_plmay be associated with faster O₂uptake (O₂) kinetics during constant-load exercise. Seven men performed cycle ergometer exercise during control (Con) and acute CA inhibition with acetazolamide (Acz,10 mg/kg body wt iv). On 6 separate days, each subject performed 6-minstep transitions in work rate from 0 to 100 W (below ventilatory threshold,<ET)or to a O₂ corresponding to~50% of the difference between the work rate atET and peakO₂(>ET).Gas exchange was measured breath by breath. Trials were interpolated at1-s intervals and ensemble averaged to yield a single response. The mean response time (MRT, i.e., time to 63% of total exponential increase) for on- and off-transients was determined using a two- (<ET) or athree-component exponential model(>ET).Arterialized venous blood was sampled from a dorsal hand vein andanalyzed for[La]_pl.MRT was similar during Con (31.2 ± 2.6 and 32.7 ± 1.2 s for onand off, respectively) and Acz (30.9 ± 3.0 and 31.4 ± 1.5 s for on and off, respectively) for work rates<ET. Atwork rates >ET, MRTwas similar between Con (69.1 ± 6.1 and 50.4 ± 3.5 s for on andoff, respectively) and Acz (69.7 ± 5.9 and 53.8 ± 3.8 s for on and off, respectively). On- and off-MRTs were slower for>ET thanfor <ETexercise.[La]_plincreased above 0-W cycling values during<ET and>ET exercise but was lower at the end of the transition during Acz (1.4 ± 0.2 and 7.1 ± 0.5 mmol/l for<ET and>ET,respectively) than during Con (2.0 ± 0.2 and 9.8 ± 0.9 mmol/lfor <ETand >ET,respectively). CA inhibition does not affectO₂ utilization at the onset of<ET or>ETexercise, suggesting that the contribution of oxidative phosphorylationto the energy demand is not affected by acute CA inhibition with Acz.

     

Delay time adjustments to minimize errors in breath-by-breath measurement of VO2 during exercise

Proctor, David N., and Kenneth C. Beck. Delay timeadjustments to minimize errors in breath-by-breath measurement of O₂ during exercise.J. Appl. Physiol. 81(6):2495-2499, 1996.If the delay time between gas concentration andflow signals is not adequately corrected during breath-by-breathanalysis of expired gas, an error in calculation of oxygen consumption(O₂) will result. Toexamine the frequency and delay time dependences of errors inO₂ measurement, six healthymen exercised at 100, 200, and 250 W on a cycle ergometer whilebreath-by-breath assessment ofO₂ was made simultaneouslywith collection of expired air. Subjects breathed first at normal rates(15-30 breaths/min) and then at 70 breaths/min. Each subjectperformed each level of exercise twice by using erroneous values forthe delay time between gas concentration and flow signals. At normalbreathing frequencies, errors inO₂ measurement were±10% over the full range of delay times used, and the errors werenot tightly correlated with variations in delay times from optimum.However, at 70 breaths/min, errors approached ±30% as thevariations in delay times deviated ±0.1 s from the optimal, and theerrors were highly correlated with the variations in delay times. Weconclude that there is greater potential for errors inO₂ measurement withincorrect delay time at higher breathing frequencies. These findingssuggest that the optimal delay time for breath-by-breath systems shouldbe adjusted by using high breathing frequencies.

     

Quantitative analysis of transpleural flux in the isolated lung

Li, M. H., J. Hildebrandt, and M. P. Hlastala.Quantitative analysis of transpleural flux in the isolated lung.J. Appl. Physiol. 82(2): 545-551, 1997.In this study, the loss of inert gas through the pleura of anisolated ventilated and perfused rabbit lung was assessed theoreticallyand experimentally. A mathematical model was used to represent an idealhomogeneous lung placed within a box with gas flow(box) surrounding the lung. Thealveoli are assumed to be ventilated with room air(A) andperfused at constant flow () containinginert gases (x) with various perfusate-air partition coefficients(_p,x).The ratio of transpleural flux of gas(pl_x)to its total delivery to the lung via pulmonary artery( ),representing fractional losses across the pleura, can be shown todepend on four dimensionless ratios:1)_p,x,2) the ratio of alveolar ventilation to perfusion(A/), 3) the ratioof the pleural diffusing capacity(Dpl_x) to the conductance ofthe alveolar ventilation (Dpl_x /A_g,where _g is the capacitancecoefficient of gas), and 4) theratio of extrapleural (box) ventilation to alveolar ventilation(box/A).Experiments were performed in isolated perfused and ventilated rabbitlungs. The perfusate was a buffer solution containing six dissolvedinert gases covering the entire 10⁵-fold range of_p,x usedin the multiple inert gas elimination technique. Steady-state inert gasconcentrations were measured in the pulmonary arterial perfusate,pulmonary venous effluent, exhaled gas, and box effluent gas. Theexperimental data could be described satisfactorily by thesingle-compartment model. It is concluded that a simple theoreticalmodel is a useful tool for predicting transpleural flux from isolatedlung preparations, with known ventilation and perfusion, for inertgases within a wide range of .

     

Effects of hypoxic hypoxia on O2 uptake and heart rate kinetics during heavy exercise

Engelen, Marielle, Janos Porszasz, Marshall Riley, KarlmanWasserman, Kazuhira Maehara, and Thomas J. Barstow. Effects ofhypoxic hypoxia on O₂ uptake andheart rate kinetics during heavy exercise. J. Appl.Physiol. 81(6): 2500-2508, 1996.It is unclearwhether hypoxia alters the kinetics ofO₂ uptake(O₂) during heavy exercise[above the lactic acidosis threshold (LAT)] and how thesealterations might be linked to the rise in blood lactate. Eight healthyvolunteers performed transitions from unloaded cycling to the sameabsolute heavy work rate for 8 min while breathing one of threeinspired O₂ concentrations: 21%(room air), 15% (mild hypoxia), and 12% (moderate hypoxia). Breathing12% O₂ slowed the time constantbut did not affect the amplitude of the primary rise inO₂ (period of first2-3 min of exercise) and had no significant effect on either thetime constant or the amplitude of the slowO₂ component (beginning2-3 min into exercise). Baseline heart rate was elevated inproportion to the severity of the hypoxia, but the amplitude andkinetics of increase during exercise and in recovery were unaffected bylevel of inspired O₂.We conclude that the predominant effect of hypoxia during heavyexercise is on the early energetics as a slowed time constant forO₂ and an additionalanaerobic contribution. However, the sum total of the processesrepresenting the slow component of O₂ is unaffected.

     

Effect of prolonged, heavy exercise on pulmonary gas exchange in athletes

During maximalexercise, ventilation-perfusion inequality increases, especially inathletes. The mechanism remains speculative. Wehypothesized that, if interstitial pulmonary edema is involved, prolonged exercise would result in increasing ventilation-perfusion inequality over time by exposing the pulmonary vascular bed to highpressures for a long duration. The response to short-term exercise wasfirst characterized in six male athletes [maximal O₂ uptake(O_{2 max}) = 63 ml · kg¹ · min¹] by using 5 minof cycling exercise at 30, 65, and 90%O_{2 max}. Multiple inert-gas, blood-gas, hemodynamic, metabolic rate, and ventilatory data were obtained. Resting log SD of the perfusion distribution (logSD) was normal [0.50 ± 0.03 (SE)] and increased with exercise (logSD = 0.65 ± 0.04, P < 0.005), alveolar-arterialO₂ difference increased (to 24 ± 3 Torr), and end-capillary pulmonary diffusion limitation occurred at 90%O_{2 max}. The subjectsrecovered for 30 min, then, after resting measurements were taken,exercised for 60 min at ~65%O_{2 max}.O₂ uptake, ventilation, cardiacoutput, and alveolar-arterial O₂difference were unchanged after the first 5 min of this test, but logSD increased from0.59 ± 0.03 at 5 min to 0.66 ± 0.05 at 60 min(P < 0.05), without pulmonary diffusion limitation. LogSD was negativelyrelated to total lung capacity normalized for body surface area(r = 0.97,P < 0.005 at 60 min). These data are compatible with interstitial edema as a mechanism and suggest that lungsize is an important determinant of the efficiency of gas exchangeduring exercise.

     

Peripheral O2 diffusion does not affect VO2 on-kinetics in isolated in situ canine muscle

To test thehypothesis that muscle O₂ uptake(O₂) on-kinetics islimited, at least in part, by peripheralO₂ diffusion, we determined theO₂ on-kinetics in1) normoxia (Control);2) hyperoxic gas breathing(Hyperoxia); and 3) hyperoxia andthe administration of a drug (RSR-13, Allos Therapeutics), whichright-shifts the Hb-O₂dissociation curve (Hyperoxia+RSR-13). The study was conducted inisolated canine gastrocnemius muscles(n = 5) during transitions from restto 3 min of electrically stimulated isometric tetanic contractions(200-ms trains, 50 Hz; 1 contraction/2 s; 60-70% peakO₂). In all conditions,before and during contractions, muscle was pump perfused withconstantly elevated blood flow (), at a levelmeasured at steady state during contractions in preliminary trials withspontaneous . Adenosine was infusedintra-arterially to prevent inordinate pressure increases with theelevated . was measuredcontinuously, arterial and popliteal venousO₂ concentrations were determinedat rest and at 5- to 7-s intervals during contractions, andO₂ was calculated as · arteriovenous O₂ content difference.PO₂ at 50%HbO₂saturation (P₅₀) was calculated.Mean capillary PO₂(c_O2)was estimated by numerical integration.P₅₀ was higher in Hyperoxia+RSR-13[40 ± 1 (SE) Torr] than in Control and in Hyperoxia (31 ± 1 Torr). After 15 s of contractions,c_O2was higher in Hyperoxia (97 ± 9 Torr) vs. Control (53 ± 3 Torr) and in Hyperoxia+RSR-13 (197 ± 39 Torr) vs. Hyperoxia. Thetime to reach 63% of the difference between baseline and steady-stateO₂ during contractions was 24.7 ± 2.7 s in Control, 26.3 ± 0.8 s in Hyperoxia, and 24.7 ± 1.1 s in Hyperoxia+RSR-13 (not significant). Enhancement ofperipheral O₂ diffusion (obtainedby increasedc_O2at constant O₂ delivery) duringthe rest-to-contraction (60-70% of peakO₂) transition did notaffect muscle O₂on-kinetics.