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.

     

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 .

     

Effect of 2,4-dinitrophenol on the hypometabolic response to hypoxia of conscious adult rats

Saiki, Chikako, and Jacopo P. Mortola. Effect of2,4-dinitrophenol on the hypometabolic response to hypoxia of conscious adult rats. J. Appl. Physiol. 83(2):537-542, 1997.During acute hypoxia, a hypometabolic response iscommonly observed in many newborn and adult mammalian species. Wehypothesized that, if hypoxic hypometabolism were entirely a regulatedresponse with no limitation in O₂availability, pharmacological uncoupling of the oxidativephosphorylation should raise O₂consumption(O₂) bysimilar amounts in hypoxia and normoxia. Metabolic, ventilatory, andcardiovascular measurements were collected from conscious rats in airand in hypoxia, both before and after intravenous injection of themitochondrial uncoupler 2,4-dinitrophenol (DNP). In hypoxia (10%O₂ breathing, 60% arterialO₂ saturation),O₂, as measured by anopen-flow technique, was less than in normoxia (~80%). SuccessiveDNP injections (6 mg/kg, 4 times) progressively increasedO₂ in both normoxia andhypoxia by similar amounts. Body temperature slightly increased innormoxia, whereas it did not change in hypoxia. The DNP-stimulatedO₂ during hypoxia couldeven exceed the control normoxic value. A single DNP injection (17 mg/kg iv) had a similar metabolic effect; it also resulted inhypotension and a drop in systemic vascular resistance. We concludethat pharmacological stimulation ofO₂ counteracts theO₂ drop determined byhypoxia and stimulates O₂not dissimilarly from normoxia. Hypoxic hypometabolism is likely toreflect a regulated process of depression of thermogenesis, with nolimitation in cellular O₂availability.

     

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 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.

     

Faster adjustment of O2 delivery does not affect VO2 on-kinetics in isolated in situ canine muscle

The mechanism(s)limiting muscle O₂ uptake(O₂) kinetics wasinvestigated in isolated canine gastrocnemius muscles(n = 7) during transitions from restto 3 min of electrically stimulated isometric tetanic contractions(200-ms trains, 50 Hz; 1 contraction/2 s; 60-70% of peakO₂). Two conditions weremainly compared: 1) spontaneousadjustment of blood flow () [control, spontaneous (C Spont)]; and2) pump-perfused, adjusted ~15 s before contractions at aconstant level corresponding to the steady-state value duringcontractions in C Spont [faster adjustment ofO₂ delivery (FastO₂ Delivery)]. During FastO₂ Delivery, 1-2 ml/min of10² M adenosine wereinfused intra-arterially to prevent inordinate pressure increases withthe elevated . The purpose of the study was todetermine whether a faster adjustment ofO₂ delivery would affectO₂ kinetics. was measured continuously; arterial(Ca_O2) and popliteal venous(Cv_O2)O₂ contents were determined atrest and at 5- to 7-s intervals during contractions;O₂ delivery was calculated as · Ca_O2,and O₂ was calculated as · arteriovenous O₂ content difference. Times toreach 63% of the difference between baseline and steady-stateO₂ during contractions were23.8 ± 2.0 (SE) s in C Spont and 21.8 ± 0.9 s in FastO₂ Delivery (not significant). Inthe present experimental model, elimination of any delay inO₂ delivery during therest-to-contraction transition did not affect muscleO₂ kinetics, which suggeststhat this kinetics was mainly set by an intrinsic inertia of oxidativemetabolism.

     

Effect of nitric oxide synthase inhibition on cardiorespiratory responses in the conscious rat

Gozal, David, José E. Torres, Yair M. Gozal, andSanford M. Littwin. Effect of nitric oxide synthase inhibition on cardiorespiratory responses in the conscious rat. J. Appl. Physiol. 81(5): 2068-2077, 1996.Nitricoxide synthase (NOS) blockade was used to test the cardioventilatoryresponses to hypercapnia and hypoxia in freely behaving animals.Chronically instrumented adult Sprague-Dawley rats were studied beforeand after intravenous administration of either 100 mg/kg ofN^G-nitro-L-arginine methylester (L-NAME), a nonspecificNOS blocker, or 10 mg/kg ofS-methyl-L-thiocitrulline(SMTC), a selective neural NOS inhibitor.L-NAME injection inducedsustained blood pressure (BP) elevation with transient tachycardia andincreased minute ventilation (E), whichreturned to baseline within minutes. SMTC elicited similar, althoughtransient, BP increases; however, heart rate andE decreased.L-NAME and SMTC did not modifyoverall steady-state hypercapnic responses. In controlconditions, hypoxia induced early Eincreases with further E enhancementsat 30 min. L-NAME increased theearly E response to 10%O₂ but induced lateE reductions in hypoxia. SMTC did notchange early E responses but inducedmarked reductions in the later Ehypoxic responses. In control animals, hypoxia induced a significantheart rate increase. This increase was absent during the early response after SMTC and was followed in bothL-NAME- and SMTC-treated animals by significant heart rate reductions to values below room air. Similarly, the sustained BP response to hypoxia in control animals wasabsent after administration of NOS inhibitors. These findings suggestthat NOS activity exerts excitatory influences on respiration andcardiac chronotropy and sustained vasomotor tone during hypoxia. Wespeculate that NOS-mediated mechanisms may play an important role inhypoxia-induced ventilatory roll-off during wakefulness.

     

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.

     

Ventilatory and metabolic responses to ambient hypoxia or hypercapnia in rats exposed to CO hypoxia

Gautier, Henry, Cristina Murariu, and Monique Bonora.Ventilatory and metabolic responses to ambient hypoxia orhypercapnia in rats exposed to CO hypoxia. J. Appl. Physiol.83(1): 253-261, 1997.We have investigated at ambienttemperatures (T_am) of 25 and5°C the effects of ambient hypoxia(Hx_am; fractional inspired O₂ = 0.14) and hypercapnia(fractional inspiredCO₂ = 0.04) on ventilation (),O₂ uptake(O₂), andcolonic temperature (T_c) in 12 conscious rats before and after carotid body denervation (CBD). Therats were concomitantly exposed to CO hypoxia (Hx_CO; fractional inspired CO = 0.03-0.05%), which decreases arterial O₂ saturation by ~25-40%.The results demonstrate the following. 1) AtT_am of 5°C, in both intact andCBD rats,/O₂ islarger when Hx_am orCO₂ is associated withHx_CO than with normoxia. At T_am of 25°C, this is also thecase except for CO₂ in CBD rats. 2) AtT_am of 5°C, the changes inO₂ andT_c seem to result from additiveeffects of the separate changes induced byHx_am,CO₂, andHx_CO. It is concluded that, inconscious rats, central hypoxia does not depress respiratory activity.On the contrary, particularly whenO₂ is augmented during acold stress, both/O₂during Hx_CO and the ventilatoryresponses to Hx_am andCO₂ are increased. The mechanismsinvolved in this relative hyperventilation are likely to involvediencephalic integrative structures.

     

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.

     

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.

     

Oxygen transport in conscious newborn dogs during hypoxic hypometabolism

We questioned whether the decrease inO₂ consumption(O₂) during hypoxia innewborns is a regulated response or reflects a limitation inO₂ availability. Experiments wereconducted on previously instrumented conscious newborn dogs.O₂ was measured at a warmambient temperature (30°C, n = 7)or in the cold (20°C, n = 6),while the animals breathed air or were sequentially exposed to 15 minof fractional inspired O₂(FI_O2): 21, 18, 15, 12, 10, 8, and 6%. In normoxia,O₂ averaged 15 ± 1 (SE)and 25 ± 1 ml · kg¹ · min¹in warm and cold conditions, respectively. In the warmcondition, hypometabolism (i.e., hypoxicO₂ < normoxicO₂) occurred at FI_O2 10%, whereas in thecold condition, hypometabolism occurred atFI_O2 12%. The sameresults were obtained in a separate group(n = 14) of noninstrumented puppies.For all levels of FI_O2 withhypometabolism, the relationships between measures ofO₂ availability (arterialO₂ saturation or content, venousPO₂ or saturation,x-axis) vs.O₂(y-axis) had lower slopes in warm than in coldconditions. Hence, O₂ during hypometabolism in the warm condition was not the maximal attainable for the level of oxygenation. The results do not support thepossibility that the hypoxic drop inO₂ in the newborn reflects a limitation in O₂availability. The results are compatible with the ideathat the phenomenon is one of "regulated conformism" tohypoxia.

     

Ventilatory long-term facilitation in unanesthetized rats

Wetested the hypothesis that unanesthetized rats exhibit ventilatorylong-term facilitation (LTF) after intermittent, but not continuous,hypoxia. Minute ventilation (E) and carbon dioxide production (CO₂) were measured inunanesthetized, unrestrained male Sprague-Dawley rats via barometricplethysmography before, during, and after exposure to continuous orintermittent hypoxia. Hypoxia was either isocapnic [inspiredO₂ fraction (FI_O2) = 0.08-0.09 and inspired CO₂ fraction(FI_CO2) = 0.04] or poikilocapnic(FI_O2 = 0.11 andFI_CO2 = 0.00). Sixty minutes afterintermittent hypoxia, E orE/CO₂ wassignificantly greater than baseline in both isocapnic and poikilocapnicconditions. In contrast, 60 min after continuous hypoxia,E andE/CO₂ were notsignificantly different from baseline values. These data demonstrateventilatory LTF after intermittent hypoxia in unanesthetized rats.Ventilatory LTF appeared similar in its magnitude (after accounting forCO₂ feedback), time course, and dependence on intermittenthypoxia to phrenic LTF previously observed in anesthetized,vagotomized, paralyzed rats.

     

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.

     

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.

     

VO2 kinetics in the horse during moderate and heavy exercise

Langsetmo, I., G. E. Weigle, M. R. Fedde, H. H. Erickson, T. J. Barstow, and D. C. Poole.O₂ kinetics in thehorse during moderate and heavy exercise. J. Appl.Physiol. 83(4): 1235-1241, 1997.The horse is asuperb athlete, achieving a maximalO₂ uptake (~160ml · min¹ · kg¹)approaching twice that of the fittest humans. Although equine O₂ uptake(O₂) kinetics arereportedly fast, they have not been precisely characterized, nor hastheir exercise intensity dependence been elucidated. To addressthese issues, adult male horses underwent incremental treadmill testingto determine their lactate threshold (T_lac) and peakO₂(O_{2 peak}),and kinetic features of their O₂ response to"square-wave" work forcings were resolved using exercisetransitions from 3 m/s to abelow-T_lac speed of 7 m/s or anabove-T_lac speed of 12.3 ± 0.7 m/s (i.e., between T_lac and O_{2 peak}) sustainedfor 6 min. O₂ andCO₂ output were measured using anopen-flow system: pulmonary artery temperature was monitored, and mixedvenous blood was sampled for plasma lactate.O₂ kinetics at work levelsbelow T_lac were well fit by atwo-phase exponential model, with a phase2 time constant(₁ = 10.0 ± 0.9 s) thatfollowed a time delay (TD₁ = 18.9 ± 1.9 s). TD₁ was similar tothat found in humans performing leg cycling exercise, but the timeconstant was substantially faster. For speeds aboveT_lac,TD₁ was unchanged (20.3 ± 1.2 s); however, the phase 2 time constantwas significantly slower (₁ = 20.7 ± 3.4 s, P < 0.05) than for exercise belowT_lac. Furthermore, in four of fivehorses, a secondary, delayed increase inO₂ became evident135.7 ± 28.5 s after the exercise transition. This "slowcomponent" accounted for ~12% (5.8 ± 2.7 l/min) of the netincrease in exercise O₂. Weconclude that, at exercise intensities below and aboveT_lac, qualitative features ofO₂ kinetics in the horseare similar to those in humans. However, at speeds belowT_lac the fast component of theresponse is more rapid than that reported for humans, likely reflectingdifferent energetics of O₂utilization within equine muscle fibers.

     

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.

     

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.

     

Determination of production of nitric oxide by lower airways of humans---theory

Hyde, Richard W., Edgar J. Geigel, Albert J. Olszowka, JohnA. Krasney, Robert E. Forster II, Mark J. Utell, and Mark W. Frampton.Determination of production of nitric oxide by the lower airwaysof humanstheory. J. Appl. Physiol.82(4): 1290-1296, 1997.Exercise and inflammatory lung disorderssuch as asthma and acute lung injury increase exhaled nitric oxide(NO). This finding is interpreted as a rise in production of NO by thelungs (NO)but fails to take into account the diffusing capacity for NO(DNO) that carries NO into thepulmonary capillary blood. We have derived equations to measureNO from thefollowing rates, which determine NO tension in the lungs(PL) at any moment from 1) production(NO);2) diffusion, whereDNO(PL) = rate of removal by lung capillary blood; and3) ventilation, whereA(PL)/(PB  47) = the rate of NO removal by alveolar ventilation(A) and PB is barometric pressure. During open-circuit breathingwhen PL is not in equilibrium,d/dtPL[V_L/(PB  47)] (where V_L is volumeof NO in the lower airways) = NO  DNO(PL)  A(PL)/(PB  47). When PL reaches asteady state so that d/dt = 0 andA iseliminated by rebreathing or breath holding, then PL = NO/DNO.PL can be interpreted as NOproduction per unit of DNO. Thisequation predicts that diseases that diminishDNO but do not alterNO willincrease expired NO levels. These equations permit precise measurementsof NO thatcan be applied to determining factors controlling NO production by thelungs.

     

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.