Effect of hemoglobin concentration on maximal O2 uptake in canine gastrocnemius muscle in situ

O2 delivery to maximally working muscle was decreased by altering hemoglobin (Hb) concentration and arterial PO2 (PaO2) to investigate whether the reductions in maximal O2 uptake (VO2max) that occur with lowered [Hb] are in part related to changes in the effective muscle O2 diffusing capacity (DmO2). Two sets of experiments were conducted. In the initial set (n = 8), three levels of Hb [5.8 +/- 0.3, 9.4 +/- 0.1, and 14.4 +/- 0.6 (SE) g/100 ml] in the blood were used in random order to pump perfuse, at equal muscle blood flows and PaO2, maximally working isolated dog gastrocnemius muscle. VO2max declined with decreasing [Hb], but the relationship between VO2max and both the effluent venous PO2 (PvO2) and the calculated mean capillary PO2 (PcO2) was not linear through the origin and, therefore, not compatible with a single value of DmO2 (as calculated by Bohr integration using a model based on Fick's law of diffusion). To clarify these results, a second set of experiments (n = 6) was conducted in which two levels of Hb (14.0 +/- 0.6 and 6.9 +/- 0.6 g/100 ml) were each combined with two levels of oxygenation (PaO2 79 +/- 8 and 29 +/- 2 Torr) and applied in random sequence to again pump perfuse maximally working dog gastrocnemius muscle at constant blood flow. In these experiments, the relationship between VO2max and both PvO2 and calculated PcO2 for each [Hb] was consistent with a constant estimate of DmO2 as PaO2 was reduced, but the calculated DmO2 for the lower [Hb] was 33% less than that at the higher [Hb] (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscle maximal O2 uptake at constant O2 delivery with and without CO in the blood

In the present study we investigated the effects of carboxyhemoglobinemia (HbCO) on muscle maximal O2 uptake (VO2max) during hypoxia. O2 uptake (VO2) was measured in isolated in situ canine gastrocnemius (n = 12) working maximally (isometric twitch contractions at 5 Hz for 3 min). The muscles were pump perfused at identical blood flow, arterial PO2 (PaO2) and total hemoglobin concentration [( Hb]) with blood containing either 1% (control) or 30% HbCO. In both conditions PaO2 was set at 30 Torr, which produced the same arterial O2 contents, and muscle blood flow was set at 120 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. To minimize CO diffusion into the tissues, perfusion with HbCO-containing blood was limited to the time of the contraction period. VO2max was 8.8 +/- 0.6 (SE) ml.min-1.100 g-1 (n = 12) with hypoxemia alone and was reduced by 26% to 6.5 +/- 0.4 ml.min-1.100 g-1 when HbCO was present (n = 12; P less than 0.01). In both cases, mean muscle effluent venous PO2 (PVO2) was the same (16 +/- 1 Torr). Because PaO2 and PVO2 were the same for both conditions, the mean capillary PO2 (estimate of mean O2 driving pressure) was probably not much different for the two conditions, even though the O2 dissociation curve was shifted to the left by HbCO. Consequently the blood-to-mitochondria O2 diffusive conductance was likely reduced by HbCO.(ABSTRACT TRUNCATED AT 250 WORDS)     

Limitation of maximal O2 uptake and performance by acute hypoxia in dog muscle in situ

The factors that determine maximal O2 uptake (VO2max) and muscle performance during severe, acute hypoxemia were studied in isolated, in situ dog gastrocnemius muscle. Our hypothesis that VO2max is limited by O2 diffusion in muscle predicts that decreases in VO2max, caused by hypoxemia, will be accompanied by proportional decreases in muscle effluent venous PO2 (PvO2). By altering the fraction of inspired O2, four levels of arterial PO2 (PaO2) [21 +/- 2, 28 +/- 1, 44 +/- 1, and 80 +/- 2 (SE) Torr] were induced in each of eight dogs. Muscle arterial and venous circulation was isolated and arterial pressure held constant by pump perfusion. Each muscle worked maximally (3 min at 5-6 Hz, isometric twitches) at each PaO2. Arterial and venous samples were taken to measure lactate, [H+], PO2, PCO2, and muscle VO2. Muscle biopsies were taken to measure [H+] (homogenate method) and lactate. VO2max decreased with PaO2 and was linearly (R = 0.99) related to both PVO2 and O2 delivery. As PaO2 fell, fatigue increased while muscle lactate and [H+] increased. Lactate release from the muscle did not change with PaO2. This suggests a barrier to lactate efflux from muscle and a possible cause of the greater fatigue seen in hypoxemia. The gas exchange data are consistent with the hypothesis that VO2max is limited by peripheral tissue diffusion of O2.     

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.

     

VO(2) on-kinetics in isolated canine muscle in situ during slowed convective O(2) delivery

The purpose of this study was to examine O(2) uptake (Vo(2)) on-kinetics when the spontaneous blood flow (and therefore O(2) delivery) on-response was slowed by 25 and 50 s. The isolated gastrocnemius muscle complex (GS) in situ was studied in six anesthetized dogs during transitions from rest to a submaximal metabolic rate (≈50-70% of peak Vo(2)). Four trials were performed: 1) a pretrial in which resting and steady-state blood flows were established, 2) a control trial in which the blood flow on-kinetics mean response time (MRT) was set at 20 s (CT20), 3) an experimental trial in which the blood flow on-kinetics MRT was set at 45 s (EX45), and 4) an experimental trial in which the blood flow on-kinetics MRT was set at 70 s (EX70). Slowing O(2) delivery via slowing blood flow on-kinetics resulted in a linear slowing of the Vo(2) on-kinetics response (R = 0.96). Average MRT values for CT20, EX45, and EX70 Vo(2) on-kinetics were (means ± SD) 17 ± 2, 23 ± 4, and 26 ± 3 s, respectively (P < 0.05 among all). During these transitions, slowing blood flow resulted in greater muscle deoxygenation (as indicated by near-infrared spectroscopy), suggesting that lower intracellular Po(2) values were reached. In this oxidative muscle, Vo(2) and O(2) delivery were closely matched during the transition period from rest to steady-state contractions. In conjunction with our previous work showing that speeding O(2) delivery did not alter Vo(2) on-kinetics under similar conditions, it appears that spontaneously perfused skeletal muscle operates at the nexus of sufficient and insufficient O(2) delivery in the transition from rest to contractions.     

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.

     

Regional intramuscular pressure development and fatigue in the canine gastrocnemius muscle in situ

Ameredes, Bill T., and Mark A. Provenzano. Regionalintramuscular pressure development and fatigue in the caninegastrocnemius muscle in situ. J. Appl.Physiol. 83(6): 1867-1876, 1997.Intramuscular pressure (P_IM) was measuredsimultaneously in zones of the medial head of thegastrocnemius-plantaris muscle group (zone I, popliteal origin; zoneII, central; zone III, near calcaneus tendon) to determine regionalmuscle mechanics during isometric tetanic contractions. PeakP_IM averages were 586, 1,676, and993 mmHg deep in zones I, II, and III and 170, 371, and 351 mmHgsuperficially in zones I, II, and III, respectively. During fatigue,loss of P_IM across zones wasgreatest in zone III (81%) and least in zone I (60%) when whole muscle tension loss was 49%. Recovery ofP_IM was greatest in zone III andleast in zone II, achieving 86% and 67% of initial P_IM, respectively, when tensionrecovered to 89%. These data demonstrate that1) regional mechanical performancecan be measured as P_IM within awhole muscle, 2)P_IM is nonuniform within thecanine gastrocnemius-plantaris muscle, being greatest in the deepcentral zone, and 3) fatigue andrecovery of P_IM are dissimilaracross regions. These differences suggest distinct local effects that integrate to determine whole muscle mechanical capacity during andafter intense exercise.

     

Longitudinal study of ventilation threshold and maximal O2 uptake in athletic boys

Ventilation threshold (VET) and peak O2 uptake (VO2max) were determined annually from ages 11 to 15 yr in 18 athletic boys. The treadmill protocol consisted of a constant-run speed with grade increments every second minute. Ventilation, VO2, and CO2 production were measured using online open-circuit spirometry. Coefficients of variation for determination of VO2max and VET were 3.4 and 5.6%, respectively. VO2max increased across age 11-15 yr, from 60.8 to 68.0 ml X kg-1 X min-1. VET at 11 yr was 34.4 and at 15 yr 41.9 ml X kg-1 X min-1, thus increasing from 56 to 62% of VO2max. Previous studies of children have shown a decline of VET relative to VO2max across age; however, in the present study the increase may have been due to the training of the boys in competitive athletics. However, the trained youth did not achieve the high relative threshold of trained adults. Across age, both VO2max and VET scaled to weight to the power 1 (in a log-log transformation). The increase in VO2max (l/min) showed greatest increments corresponding to gains in size (a growth curve), whereas increases of VET were consistent year to year. Thus VET was altered independently of VO2max. Factors other than size (and presumably muscle mass) such as the maturation of an enzymatic profile of fast glycolytic fibers might have an important influence on the threshold during youth.     

Force-velocity shifts with repetitive isometric and isotonic contractions of canine gastrocnemius in situ.

The force-velocity (F-V) relationships of canine gastrocnemius-plantaris muscles at optimal muscle length in situ were studied before and after 10 min of repetitive isometric or isotonic tetanic contractions induced by electrical stimulation of the sciatic nerve (200-ms trains, 50 impulses/s, 1 contraction/s). F-V relationships and maximal velocity of shortening (Vmax) were determined by curve fitting with the Hill equation. Mean Vmax before fatigue was 3.8 +/- 0.2 (SE) average fiber lengths/s; mean maximal isometric tension (Po) was 508 +/- 15 g/g. With a significant decrease of force development during isometric contractions (-27 +/- 4%, P < 0.01, n = 5), Vmax was unchanged. However, with repetitive isotonic contractions at a low load (P/Po = 0.25, n = 5), a significant decrease in Vmax was observed (-21 +/- 2%, P < 0.01), whereas Po was unchanged. Isotonic contractions at an intermediate load (P/Po = 0.5, n = 4) resulted in significant decreases in both Vmax (-26 +/- 6%, P < 0.05) and Po (-12 +/- 2%, P < 0.01). These results show that repeated contractions of canine skeletal muscle produce specific changes in the F-V relationship that are dependent on the type of contractions being performed and indicate that decreases in other contractile properties, such as velocity development and shortening, can occur independently of changes in isometric tension.     

Increased plasma O2 solubility improves O2 uptake of in situ dog muscle working maximally.

A perfluorocarbon emulsion [formulation containing 90% wt/vol perflubron (perfluorooctylbromide); Alliance Pharmaceutical] was used to increase O2 solubility in the plasma compartment during hyperoxic low hemoglobin concentration ([Hb]) perfusion of a maximally working dog muscle in situ. Our hypothesis was that the increased plasma O2 solubility would increase the muscle O2 diffusing capacity (DO2) by augmenting the capillary surface area in contact with high [O2]. Oxygen uptake (VO2) was measured in isolated in situ canine gastrocnemius (n = 4) while working for 6 min at a maximal stimulation rate of 1 Hz (isometric tetanic contractions) on three to four separate occasions for each muscle. On each occasion, the last 4 min of the 6-min work period was split into 2 min of a control treatment (only emulsifying agent mixed into blood) and 2 min of perflubron treatment (6 g/kg body wt), reversing the order for each subsequent work bout. Before contractions, the [Hb] of the dog was decreased to 8-9 g/100 ml and arterial PO2 was increased to 500-600 Torr by having the dog breathe 100% O2 to maximize the effect of the perflubron. Muscle blood flow was held constant between the two experimental conditions. Plasma O2 solubility was almost doubled to 0.005 ml O2 x 100 ml blood-1 x Torr-1 by the addition of the perflubron. Muscle O2 delivery and maximal VO2 were significantly improved (at the same blood flow and [Hb]) by 11 and 12.6%, respectively (P < 0.05), during the perflubron treatment compared with the control. O2 extraction by the muscle remained the same between the two treatments, as did the estimate of DO2.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.

     

Dissociation of phosphohistone phosphatases from canine heart.

Phosphohistone phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) of canine heart extract has been separated by DEAE-cellulose chromatography into 4 molecular forms, namely phosphatases A (Mr = 156 000), B (Mr = 161 000), C (Mr = 95 600) and U (Mr = 61 000). ATP inhibited phosphatase A, stimulated phosphatase B and did not significantly affect phosphatase C activity. Phosphatase U requires Mn2+ for activity, under which condition ATP is inhibitory. Phosphatases A, B and C, but not phosphatase U, were dissociated by ethanol into catalytic subunits that were inhibited by ATP, insensitive to Mn2+, and had a common molecular weight of 34 800 (phosphatase S). The dissociation was accompanied by an increase of enzymic activity. Chromatography of the ethanol-treated 55% (NH4)2SO4 fraction of canine heart extract on DEAE-cellulose demonstrated that the multiple forms of phosphohistone phosphatase could be reduced to two forms: phosphatase U and phosphatase S, which may represent two basic constituents of the multiple forms of phosphohistone phosphatase in canine heart.     

Effects of acetazolamide on metabolic and respiratory responses to exercise at maximal O2 uptake

Changes in blood gases, ions, lactate, pH, hemoglobin, blood temperature, total body metabolism, and muscle metabolites were measured before and during exercise (except muscle), at fatigue, and during recovery in normal and acetazolamide-treated horses to test the hypothesis that an acetazolamide-induced acidosis would compromise the metabolism of the horse exercising at maximal O2 uptake. Acetazolamide-treated horses had a 13-mmol/l base deficit at rest, higher arterial Po2 at rest and during exercise, higher arterial and mixed venous Pco2 during exercise, and a 48-s reduction in run time. Arterial pH was lower during exercise but not in recovery after acetazolamide. Blood temperature responses were unaffected by acetazolamide administration. O2 uptake was similar during exercise and recovery after acetazolamide treatment, whereas CO2 production was lower during exercise. Muscle [glycogen] and pH were lower at rest, whereas heart rate, muscle pH and [lactate], and plasma [lactate] and [K+] were lower and plasma [Cl-] higher following exercise after acetazolamide treatment. These data demonstrate that acetazolamide treatment aggravates the CO2 retention and acidosis occurring in the horse during heavy exercise. This could negatively affect muscle metabolism and exercise capacity.     

Determinants of maximal O(2) uptake in rats selectively bred for endurance running capacity.

O(2) transport during maximal exercise was studied in rats bred for extremes of exercise endurance, to determine whether maximal O(2) uptake (VO(2 max)) was different in high- (HCR) and low-capacity runners (LCR) and, if so, which were the phenotypes responsible for the difference. VO(2 max) was determined in five HCR and six LCR female rats by use of a progressive treadmill exercise protocol at inspired PO(2) of approximately 145 (normoxia) and approximately 70 Torr (hypoxia). Normoxic VO(2 max) (in ml. min(-1). kg(-1)) was 64.4 +/- 0.4 and 57.6 +/- 1.5 (P < 0.05), whereas VO(2 max) in hypoxia was 42.7 +/- 0.8 and 35.3 +/- 1.5 (P < 0.05) in HCR and LCR, respectively. Lack of significant differences between HCR and LCR in alveolar ventilation, alveolar-to-arterial PO(2) difference, or lung O(2) diffusing capacity indicated that neither ventilation nor efficacy of gas exchange contributed to the difference in VO(2 max) between groups. Maximal rate of blood O(2) convection (cardiac output times arterial blood O(2) content) was also similar in both groups. The major difference observed was in capillary-to-tissue O(2) transfer: both the O(2) extraction ratio (0.81 +/- 0.002 in HCR, 0.74 +/- 0.009 in LCR, P < 0.001) and the tissue diffusion capacity (1.18 +/- 0.09 in HCR and 0.92 +/- 0.05 ml. min(-1). kg(-1). Torr(-1) in LCR, P < 0.01) were significantly higher in HCR. The data indicate that selective breeding for exercise endurance resulted in higher VO(2 max) mostly associated with a higher transfer of O(2) at the tissue level.     

Endotoxemia decreases matching of regional blood flow and O2 delivery to O2 uptake in the porcine left ventricle

Heterogeneity of regional coronary blood flow is caused in part by heterogeneity in O(2) demand in the normal heart. We investigated whether myocardial O(2) supply/demand mismatching is associated with the myocardial depression of sepsis. Regional blood flow (microspheres) and O(2) uptake ([(13)C]acetate infusion and analysis of resultant NMR spectra) were measured in about nine contiguous tissue samples from the left ventricle (LV) in each heart. Endotoxemic pigs (n = 9) showed hypotension at unchanged cardiac output with a fall in LV stroke work and first derivative of LV pressure relative to controls (n = 4). Global coronary blood flow and O(2) delivery were maintained. Lactate accumulated in arterial blood, but net lactate extraction across the coronary bed was unchanged during endotoxemia. When LV O(2) uptake based on blood gas versus NMR data were compared, the correlation was 0.73 (P = 0.007). While stable over time in controls, regional blood flows were strongly redistributed during endotoxin shock, with overall flow heterogeneity unchanged. A stronger redistribution of blood flow with endotoxin was associated with a larger fall in LV function parameters. Moreover, the correlation of regional O(2) delivery to uptake fell from r = 0.73 (P < 0.001) in control to r = 0.18 (P = 0.25, P = 0.009 vs. control) in endotoxemic hearts. The results suggest a redistribution of LV regional coronary blood flow during endotoxin shock in pigs, with regional O(2) delivery mismatched to O(2) demand. Mismatching may underlie, at least in part, the myocardial depression of sepsis.     

Maximal O2 uptake of in situ dog muscle during acute hypoxemia with constant perfusion

We investigated the relationships among maximal O2 uptake (VO2max), effluent venous PO2 (PvO2), and calculated mean capillary PO2 (PCO2) in isolated dog gastrocnemius in situ as arterial PO2 (PaO2) was progressively reduced with muscle blood flow held constant. The hypothesis that VO2max is determined in part by peripheral tissue O2 diffusion predicts proportional declines in VO2max and PCO2 if the diffusing capacity of the muscle remains constant. The inspired O2 fraction was altered in each of six dogs to produce four different levels of PaO2 [22 +/- 2, 29 +/- 1, 38 +/- 1, and 79 +/- 4 (SE) Torr]. Muscle blood flow, with the circulation isolated, was held constant at 122 +/- 15 ml.100 g-1.min-1 while the muscle worked maximally (isometric twitches at 5-7 Hz) at each of the four different values of PaO2. Arterial and venous samples were taken to measure lactate, pH, PO2, PCO2, and muscle VO2. PCO2 was calculated using Fick's law of diffusion and a Bohr integration procedure. VO2max fell progressively (P less than 0.01) with decreasing PaO2. The decline in VO2max was proportional (R = 0.99) to the fall in both muscle PvO2 and calculated PCO2 while the calculated muscle diffusing capacity was not different among the four conditions. Fatigue developed more rapidly with lower PaO2, although lactate output from the muscle was not different among conditions. These results are consistent with the hypothesis that resistance to O2 diffusion in the peripheral tissue may be a principal determinant of VO2max.