Influence of age and gender on cardiac output-VO2 relationships during submaximal cycle ergometry

Proctor, David N., Kenneth C. Beck, Peter H. Shen, Tamara J. Eickhoff, John R. Halliwill, and Michael J. Joyner. Influence ofage and gender on cardiacoutput-O₂ relationshipsduring submaximal cycle ergometry. J. Appl.Physiol. 84(2): 599-605, 1998.It is presentlyunclear how gender, aging, and physical activity status interact todetermine the magnitude of the rise in cardiac output(c) during dynamic exercise. To clarify this issue,the present study examined thec-O₂ uptake(O₂) relationship duringgraded leg cycle ergometry in 30 chronically endurance-trained subjects from four groups (n = 6-8/group): younger men (20-30 yr), older men (56-72yr), younger women (24-31 yr), and older women(51-72 yr). c (acetylene rebreathing), strokevolume (c/heart rate), and whole bodyO₂ were measured at restand during submaximal exercise intensities (40, 70, and ~90% of peakO₂). Baseline restinglevels of c were 0.6-1.2 l/min less in theolder groups. However, the slopes of thec-O₂relationship across submaximal levels of cycling were similar among allfour groups (5.4-5.9 l/l). The absolute cassociated with a given O₂(1.0-2.0 l/min) was also similar among groups. Resting andexercise stroke volumes (ml/beat) were lower in women than in men butdid not differ among age groups. However, older men and women showed areduced ability, relative to their younger counterparts, to maintainstroke volume at exercise intensities above 70% of peakO₂. This latter effect wasmost prominent in the oldest women. These findings suggest that neitherage nor gender has a significant impact on thec-O₂ relationships during submaximal cycle ergometry among chronically endurance-trained individuals.

     

Contributions of pulmonary perfusion and ventilation to heterogeneity in VA/Q measured by PET

Treppo, Steven, Srboljub M. Mijailovich, and José G. Venegas. Contributions of pulmonary perfusion and ventilation toheterogeneity in A/measured by PET. J. Appl. Physiol. 82(4): 1163-1176, 1997. To estimate the contributions of the heterogeneity in regionalperfusion () and alveolar ventilation(A) to that of ventilation-perfusionratio (A/), we haverefined positron emission tomography (PET) techniques to image localdistributions of andA per unit of gas volume content(s and sA,respectively) and VA/ indogs. sA was assessed in two ways:1) the washout of ¹³NN tracer after equilibrationby rebreathing (sA_i), and2) the ratio of an apneic image after a bolus intravenousinfusion of ¹³NN-saline solution to an image collectedduring a steady-state intravenous infusion of the same solution(sA_p).sA_p was systematically higher than sA_i in allanimals, and there was a high spatial correlation betweens andsA_p in both body positions(mean correlation was 0.69 prone and 0.81 supine) suggesting thatventilation to well-perfused units was higher than to those poorlyperfused. In the prone position, the spatial distributions ofs, sA_p, and A/ were fairlyuniform with no significant gravitational gradients; however, in thesupine position, these variables were significantly more heterogeneous,mostly because of significant gravitational gradients (15, 5.5, and10%/cm, respectively) accounting for 73, 33, and 66% of thecorresponding coefficient of variation (CV)² values. Weconclude that, in the prone position, gravitational forces in blood andlung tissues are largely balanced out by dorsoventral differences inlung structure. In the supine position, effects of gravity andstructure become additive, resulting in substantial gravitationalgradients in s andsA_p, with the higherheterogeneity inA/ caused by agravitational gradient in s, only partially compensated by that in sA.

     

Mitochondrial redox state as a potential detector of liver dysoxia in vivo

Dysoxia canbe defined as ATP flux decreasing in proportion toO₂ availability with preserved ATPdemand. Hepatic venous -hydroxybutyrate-to-acetoacetate ratio(-OHB/AcAc) estimates liver mitochondrial NADH/NAD and may detectthe onset of dysoxia. During partial dysoxia (as opposed to anoxia),however, flow may be adequate in some liver regions, diluting effluentfrom dysoxic regions, thereby rendering venous -OHB/AcAc unreliable.To address this concern, we estimated tissue ATP whilegradually reducing liver blood flow of swine to zero in a nuclearmagnetic resonance spectrometer. ATP flux decreasing withO₂ availability was taken asO₂ uptake(O₂) decreasing inproportion to O₂ delivery(O₂);and preserved ATP demand was taken as increasingP_i/ATP.O₂, tissueP_i/ATP, and venous -OHB/AcAcwere plotted againstO₂to identify critical inflection points. Tissue dysoxia required meanO₂for the group to be critical for bothO₂ and forP_i/ATP. CriticalO₂values for O₂ andP_i/ATP of 4.07 ± 1.07 and 2.39 ± 1.18 (SE) ml · 100 g¹ · min¹,respectively, were not statistically significantly different but notclearly the same, suggesting the possibility that dysoxia might havecommenced after O₂ begandecreasing, i.e., that there could have been"O₂ conformity." CriticalO₂for venous -OHB/AcAc was 2.44 ± 0.46 ml · 100 g¹ · min¹(P = NS), nearly the same as that forP_i/ATP, supporting venous -OHB/AcAc as a detector of dysoxia. All issues considered, tissue mitochondrial redox state seems to be an appropriate detector ofdysoxia in liver.

     

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.

     

Increasing maximal heart rate increases maximal O2 uptake in rats acclimatized to simulated altitude

Gonzalez, Norberto C., Richard L. Clancy, Yoshihiro Moue,and Jean-Paul Richalet. Increasing maximal heart rate increases maximal O₂ uptake in ratsacclimatized to simulated altitude. J. Appl.Physiol. 84(1): 164-168, 1998.Maximal exerciseheart rate (HR_max) is reducedafter acclimatization to hypobaric hypoxia. The lowHR_max contributes to reducemaximal cardiac output(_max) andmay limit maximal O₂ uptake(O_{2 max}). Theobjective of these experiments was to test the hypothesisthat the reduction in_max afteracclimatization to hypoxia, due, in part, to the lowHR_max, limitsO_{2 max}. Ifthis hypothesis is correct, an increase in _max wouldresult in a proportionate increase inO_{2 max}. Rats acclimatized to hypobaric hypoxia [inspiredPO₂(PI_O2) = 69.8 ± 3 Torr for 3 wk] exercised on a treadmill in hypoxic (PI_O2 = 71.7 ± 1.1 Torr) or normoxic conditions(PI_O2 = 142.1 ± 1.1 Torr). Each rat ran twice: in one bout the rat was allowed to reach itsspontaneous HR_max, which was 505 ± 7 and 501 ± 5 beats/min in hypoxic and normoxic exercise,respectively; in the other exercise bout,HR_max was increased by 20% to the preacclimatization value of 600 beats/min by atrial pacing. This resulted in an ~10% increase in_max, since theincrease in HR_max was offset by a10% decrease in stroke volume, probably due to shortening of diastolicfilling time. The increase in_max was accompanied by a proportionate increase in maximal rate of convective O₂ delivery(_max × arterial O₂ content), maximal workrate, and O_{2 max} inhypoxic and normoxic exercise. The data show that increasingHR_max topreacclimatization levels increasesO_{2 max}, supportingthe hypothesis that the lowHR_max tends to limitO_{2 max} after acclimatization to hypoxia.

     

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.

     

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.

     

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.

     

Quantitative methanol-burning lung model for validating gas-exchange measurements over wide ranges of FIO2

Themethanol-burning lung model has been used as a technique for generatinga predictable ratio of carbon dioxide production (CO₂) to oxygen consumption(O₂) or respiratoryquotient (RQ). Although an accurate RQ can be generated, quantitativelypredictable and adjustableO₂ andCO₂ cannot be generated. Wedescribe a new burner device in which the combustion rate of methanolis always equal to the infusion rate of fuel over an extended range ofO₂ concentrations. This permitsthe assembly of a methanol-burning lung model that is usable withO₂ concentrations up to 100% and provides continuously adjustable and quantitativeO₂ (69-1,525 ml/min)and CO₂ (46-1,016ml/min) at a RQ of 0.667.

     

Effect of prolonged heavy exercise on pulmonary gas exchange in horses

During short-term maximal exercise,horses have impaired pulmonary gas exchange, manifested by diffusionlimitation and arterial hypoxemia, without marked ventilation-perfusion(A/)inequality. Whether gas exchange deteriorates progressively duringprolonged submaximal exercise has not been investigated. Sixthoroughbred horses performed treadmill exercise at ~60% of maximaloxygen uptake until exhaustion (28-39 min). Multipleinert gas, blood-gas, hemodynamic, metabolic rate, and ventilatory datawere obtained at rest and 5-min intervals during exercise. Oxygenuptake, cardiac output, and alveolar-arterialPO₂ gradient were unchanged after thefirst 5 min of exercise. Alveolar ventilation increased progressivelyduring exercise, from increased tidal volume and respiratory frequency,resulting in an increase in arterialPO₂ and decrease in arterialPCO₂. At rest there was minimal A/inequality, log SD of the perfusion distribution (logSD) = 0.20. This doubled by 5 min of exercise (logSD = 0.40) butdid not increase further. There was no evidence of alveolar-end-capillary diffusion limitation during exercise. However, there was evidence for gas-phase diffusion limitation at all time points, and enflurane was preferentially overretained. Horses maintainexcellent pulmonary gas exchange during exhaustive, submaximal exercise. AlthoughA/inequality is greater than at rest, it is less than observed in mostmammals and the effect on gas exchange is minimal.

     

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.

     

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 .

     

Differences in skeletal muscle between men and women with chronic heart failure

Men with chronic heart failure (CHF) have alterationsin their skeletal muscle that are partially responsible for a decreased exercise tolerance. The purpose of this study was to investigate whether skeletal muscle alterations in women with CHF are similar tothose observed in men and if these alterations are related to exerciseintolerance. Twenty-five men and thirteen women with CHFperformed a maximal exercise test for evaluation of peak oxygen consumption (O₂) and resting leftventricular ejection fraction, after which a biopsy of the vastuslateralis was performed. Twenty-one normal subjects (11 women, 10 men)were also studied. The relationship between muscle markers and peakO₂ was consistent for CHF men and women.When controlling for gender, analysis showed that oxidative enzymes andcapillary density are the best predictors of peak O_2. These results indicatethat aerobically matched CHF men and women have no differences inskeletal muscle biochemistry and histology. However, when CHF groupswere separated by peak exercise capacity of 4.5 metabolic equivalents(METs), CHF men with peak O₂ >4.5METs had increased citrate synthase and 3-hydroxyacyl-CoA dehydrogenasecompared with CHF men with peak O₂ <4.5METs. CHF men with a lower peak O₂ hadincreased capillary density compared with men with higher peakO₂. These observations were notreproduced in CHF women. This suggests that differences may existin how skeletal muscle adapts to decreasing peakO₂ in patients with CHF.

     

Mechanical and metabolic determination of VO2 and fatigue during repetitive isometric contractions in situ

Repetitiveisometric tetanic contractions (1/s) of the caninegastrocnemius-plantaris muscle were studied either at optimal length(L_o) or shortlength (L_s;~0.9 · L_o),to determine the effects of initial length on mechanical and metabolicperformance in situ. Respective averages of mechanical and metabolicvariables were(L_o vs.L_s, allP < 0.05) passive tension (preload) = 55 vs. 6 g/g, maximal active tetanic tension(P_o) = 544 vs. 174 (0.38 · P_o)g/g, maximal blood flow () = 2.0 vs. 1.4 ml · min¹ · g¹,and maximal oxygen uptake(O₂) = 12 vs. 9 µmol · min¹ · g¹.Tension at L_odecreased to0.64 · P_o over20 min of repetitive contractions, demonstrating fatigue; there were nosignificant changes in tension atL_s. In separatemuscles contracting atL_o, was set to that measured atL_s (1.1 ml · min¹ · g¹),resulting in decreased O₂(7 µmol · min¹ · g¹),and rapid fatigue, to0.44 · P_o. Thesedata demonstrate that 1)muscles at L_ohave higher andO₂ values than those at L_s;2) fatigue occurs atL_o with highO₂, adjusting metabolic demand (tension output) to match supply; and3) the lack of fatigue atL_s with lowertension, , andO₂ suggestsadequate matching of metabolic demand, set low by shortmuscle length, with supply optimized by low preload. Thesedifferences in tension andO₂ betweenL_o andL_s groupsindicate that muscles contracting isometrically at initial lengthsshorter than L_oare working under submaximal conditions.

     

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.

     

Ventilation-perfusion alterations after smoke inhalation injury in an ovine model

Shimazu, Takeshi, Tetsuo Yukioka, Hisashi Ikeuchi, Arthur D. Mason, Jr., Peter D. Wagner, and Basil A. Pruitt, Jr.Ventilation-perfusion alterations after smoke inhalation injury inan ovine model. J. Appl. Physiol.81(5): 2250-2259, 1996.To study the pathophysiological mechanismof progressive hypoxemia after smoke inhalation injury, alterations inventilation-perfusion ratio(A/)were studied in an ovine model by using the multiple inert gaselimination technique. Because ethane was detected in expired gas ofsome sheep, we replaced ethane with krypton, which was a uniqueapplication of the multiple inert gas elimination technique when one ofthe experimental gases is present in the inspirate. Severity-related changes were studied 24 h after injury in control and mild, moderate, and severe inhalation injury groups. Time-related changes were studiedin controls and sheep with moderate injury at 6, 12, 24, and 72 h.Arterial PO₂ decreased progressivelywith severity of injury as well as with time. In smoke-exposed animals,blood flow was recruited to lowA/compartment (0 < A/ < 0.1; 17.6 ± 10.6% of cardiac output, 24 h,moderate injury) from normal A/compartment (0.1 < A/ < 10). However, increases in true shunt(A/ = 0; 5.6 ± 2.5%, 24 h, moderate injury) and dead space were notconsistent findings. TheA/patterns suggest the primary change in smoke inhalation injury to be adisturbance of ventilation.

     

VO2 max is associated with ACE genotype in postmenopausal women

Relationships have frequently been found betweenangiotensin-converting enzyme (ACE) genotype and various pathologicaland physiological cardiovascular outcomes and functions. Thuswe sought to determine whether ACE genotype affected maximalO₂ consumption (O_{2 max}) and maximalexercise hemodynamics in postmenopausal women with different habitualphysical activity levels. Age, body composition, and habitual physicalactivity levels did not differ among ACE genotype groups. However, ACEinsertion/insertion (II) genotype carriers had a 6.3 ml · kg¹ · min¹higher O_{2 max}(P < 0.05) than the ACEdeletion/deletion (DD) genotype group after accounting for the effectof physical activity levels. The ACE II genotype group also had a 3.3 ml · kg¹ · min¹higher O_{2 max}(P < 0.05) than the ACEinsertion/deletion (ID) genotype group. The ACE ID group tended to havea higher O_{2 max} thanthe DD genotype group, but the difference was not significant. ACEgenotype accounted for 12% of the variation inO_{2 max} among womenafter accounting for the effect of habitual physical activity levels.The entire difference inO_{2 max} among ACEgenotype groups was the result of differences in maximal arteriovenousO₂ difference (a-vDO₂).ACE genotype accounted for 17% of the variation in maximal a-vDO₂ inthese women. Maximal cardiac output index did not differ whatsoeveramong ACE genotype groups. Thus it appears that ACE genotype accountsfor a significant portion of the interindividual differences inO_{2 max} among thesewomen. However, this difference is the result of genotype-dependentdifferences in maximala-vDO₂ andnot of maximal stroke volume and maximal cardiac output.

     

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.

     

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.

     

Kinetics of oxygen uptake at the onset of exercise in boys and men

The objective of this study was to compare theO₂ uptake(O₂) kinetics at the onsetof heavy exercise in boys and men. Nine boys, aged 9-12 yr, and 8 men, aged 19-27 yr, performed a continuous incremental cyclingtask to determine peak O₂(O_{2 peak}).On 2 other days, subjects performed each day four cycling tasks at 80 rpm, each consisting of 2 min of unloaded cycling followed twice bycycling at 50%O_{2 peak} for 3.5 min,once by cycling at 100%O_{2 peak} for 2 min,and once by cycling at 130%O_{2 peak} for 75 s.O₂ deficit was not significantlydifferent between boys and men (respectively, 50%O_{2 peak} task: 6.6 ± 11.1 vs. 5.5 ± 7.3 ml · min¹ · kg¹;100% O_{2 peak} task:28.5 ± 8.1 vs. 31.8 ± 6.3 ml · min¹ · kg¹;and 130%O_{2 peak}task: 30.1 ± 5.7 vs. 35.8 ± 5.3 ml · min¹ · kg¹).To assess the kinetics, phase I was excluded from analysis. Phase IIO₂ kinetics could bedescribed in all cases by a monoexponential function. ANOVA revealed nodifferences in time constants between boys and men (respectively, 50%O_{2 peak}task: 22.8 ± 5.1 vs. 26.4 ± 4.1 s; 100%O_{2 peak} task: 28.0 ± 6.0 vs. 28.1 ± 4.4 s; and 130%O_{2 peak} task: 19.8 ± 4.1 vs. 20.7 ± 5.7 s). In conclusion, O₂ deficit and fast-componentO₂ on-transientsare similar in boys and men, even at high exercise intensities, whichis in contrast to the findings of other studies employing simplermethods of analysis. The previous interpretation that children relyless on nonoxidative energy pathways at the onset of heavy exercise isnot supported by our findings.