Dissociation of maximal O2 uptake from O2 delivery in canine gastrocnemius in situ

To test the hypothesis that maximal O2 uptake (VO2max) can be limited by O2 diffusion in the peripheral tissue, we kept O2 delivery [blood flow X arterial O2 content (CaO2)] to maximally contracting muscle equal between 1) low flow-high CaO2 and 2) high flow-low CaO2 conditions. The hypothesis predicts, because of differences in the capillary PO2 profile, that the former condition will result in both a higher VO2max and muscle effluent venous PO2 (PVO2). We studied the relations among VO2max, PVO2, and O2 delivery during maximal isometric contractions in isolated, in situ dog gastrocnemius muscle (n = 6) during these two conditions. O2 delivery was matched by varying arterial O2 partial pressure and adjusting flow to the muscle accordingly. A total of 18 matched O2 delivery pairs were obtained. As planned, O2 delivery was not significantly different between the two treatments. In contrast, VO2max was significantly higher [10.4 +/- 0.5 (SE) ml.100 g-1.min-1; P = 0.01], as was PVO2 (25 +/- 1 Torr; P less than 0.01) in the low flow-high CaO2 treatment compared with the high flow-low CaO2 treatment (9.1 +/- 0.4 ml.100 g-1.min-1 and 20 +/- 1 Torr, respectively). The rate of fatigue was greater in the high flow-low CaO2 condition, as was lactate output from the muscle and muscle lactate concentration. The results of this study show that VO2max is not uniquely dependent on O2 delivery and support the hypothesis that VO2max can be limited by peripheral tissue O2 diffusion.     

Muscle chemoreflex elevates muscle blood flow and O2 uptake at exercise onset in nonischemic human forearm.

We tested the hypothesis that increases in forearm blood flow (FBF) during the adaptive phase at the onset of moderate exercise would allow a more rapid increase in muscle O2 uptake (VO2 mus). Fifteen subjects completed forearm exercise in control (Con) and leg occlusion (Occ) conditions. In Occ, exercise of ischemic calf muscles was performed before the onset of forearm exercise to activate the muscle chemoreflex evoking a 25-mmHg increase in mean arterial pressure that was sustained during forearm exercise. Eight subjects who increased FBF during Occ compared with Con in the adaptation phase by >30 ml/min were considered "responders." For the responders, a higher VO2 mus accompanied the higher FBF only during the adaptive phase of the Occ tests, whereas there was no difference in the baseline or steady-state FBF or VO2 mus between Occ and Con. Supplying more blood flow at the onset of exercise allowed a more rapid increase in VO2 mus supporting our hypothesis that, at least for this type of exercise, O2 supply might be limiting.     

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.     

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.     

Muscle capillary blood flow kinetics estimated from pulmonary O2 uptake and near-infrared spectroscopy.

The near-infrared spectroscopy (NIRS) signal (deoxyhemoglobin concentration; [HHb]) reflects the dynamic balance between muscle capillary blood flow (Q(cap)) and muscle O(2) uptake (Vo(2)(m)) in the microcirculation. The purposes of the present study were to estimate the time course of Q(cap) from the kinetics of the primary component of pulmonary O(2) uptake (Vo(2)(p)) and [HHb] throughout exercise, and compare the Q(cap) kinetics with the Vo(2)(p) kinetics. Nine subjects performed moderate- (M; below lactate threshold) and heavy-intensity (H, above lactate threshold) constant-work-rate tests. Vo(2)(p) (l/min) was measured breath by breath, and [HHb] (muM) was measured by NIRS during the tests. The time course of Q(cap) was estimated from the rearrangement of the Fick equation [Q(cap) = Vo(2)(m)/(a-v)O(2), where (a-v)O(2) is arteriovenous O(2) difference] using Vo(2)(p) (primary component) and [HHb] as proxies of Vo(2)(m) and (a-v)O(2), respectively. The kinetics of [HHb] [time constant (tau) + time delay [HHb]; M = 17.8 +/- 2.3 s and H = 13.7 +/- 1.4 s] were significantly (P < 0.001) faster than the kinetics of Vo(2) [tau of primary component (tau(P)); M = 25.5 +/- 8.8 s and H = 25.6 +/- 7.2 s] and Q(cap) [mean response time (MRT); M = 25.4 +/- 9.1 s and H = 25.7 +/- 7.7 s]. However, there was no significant difference between MRT of Q(cap) and tau(P)-Vo(2) for both intensities (P = 0.99), and these parameters were significantly correlated (M and H; r = 0.99; P < 0.001). In conclusion, we have proposed a new method to noninvasively approximate Q(cap) kinetics in humans during exercise. The resulting overall Q(cap) kinetics appeared to be tightly coupled to the temporal profile of Vo(2)(m).     

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.

     

Muscle mitochondrial capacity exceeds maximal oxygen delivery in humans

Across a wide range of species and body mass a close matching exists between maximal conductive oxygen delivery and mitochondrial respiratory rate. In this study we investigated in humans how closely in-vivo maximal oxygen consumption (VO(2) max) is matched to state 3 muscle mitochondrial respiration. High resolution respirometry was used to quantify mitochondrial respiration from the biopsies of arm and leg muscles while in-vivo arm and leg VO(2) were determined by the Fick method during leg cycling and arm cranking. We hypothesized that muscle mitochondrial respiratory rate exceeds that of systemic oxygen delivery. The state 3 mitochondrial respiration of the deltoid muscle (4.3±0.4 mmol o(2)kg(-1) min(-1)) was similar to the in-vivo VO(2) during maximal arm cranking (4.7±0.5 mmol O(2) kg(-1) min(-1)) with 6 kg muscle. In contrast, the mitochondrial state 3 of the quadriceps was 6.9±0.5 mmol O(2) kg(-1) min(-1), exceeding the in-vivo leg VO(2) max (5.0±0.2 mmol O(2) kg(-1) min(-1)) during leg cycling with 20 kg muscle (P<0.05). Thus, when half or more of the body muscle mass is engaged during exercise, muscle mitochondrial respiratory capacity surpasses in-vivo VO(2) max. The findings reveal an excess capacity of muscle mitochondrial respiratory rate over O(2) delivery by the circulation in the cascade defining maximal oxidative rate in humans.     

Muscle fiber recruitment and the slow component of O2 uptake: constant work rate vs. all-out sprint exercise

The slow component of pulmonary O(2) uptake (Vo(2)) during constant work rate (CWR) high-intensity exercise has been attributed to the progressive recruitment of (type II) muscle fibers. We tested the following hypotheses: 1) the Vo(2) slow component gain would be greater in a 3-min all-out cycle test than in a work-matched CWR test, and 2) the all-out test would be associated with a progressive decline, and the CWR test with a progressive increase, in muscle activation, as estimated from the electromyogram (EMG) of the vastus lateralis muscle. Eight men (aged 21-39 yr) completed a ramp incremental test, a 3-min all-out test, and a work- and time-matched CWR test to exhaustion. The maximum Vo(2) attained in an initial ramp incremental test (3.97 ± 0.83 l/min) was reached in both experimental tests (3.99 ± 0.84 and 4.03 ± 0.76 l/min for all-out and CWR, respectively). The Vo(2) slow component was greater (P < 0.05) in the all-out test (1.21 ± 0.31 l/min, 4.2 ± 2.2 ml·min(-1)·W(-1)) than in the CWR test (0.59 ± 0.22 l/min, 1.70 ± 0.5 ml·min(-1)·W(-1)). The integrated EMG declined by 26% (P < 0.001) during the all-out test and increased by 60% (P < 0.05) during the CWR test from the first 30 s to the last 30 s of exercise. The considerable reduction in muscle efficiency in the all-out test in the face of a progressively falling integrated EMG indicates that progressive fiber recruitment is not requisite for development of the Vo(2) slow component during voluntary exercise in humans.     

Increased VO2 max with right-shifted Hb-O2 dissociation curve at a constant O2 delivery in dog muscle in situ

If the diffusive component ofO₂ transport in muscle isimportant in determining exercise capacity, an increasedcapillary-to-tissue PO₂ differenceshould enhance gas exchange from blood to skeletal muscle duringexercise. Thus a rightward shift in theO₂ dissociation curve shouldtheoretically increase O₂extraction and improve maximal O₂uptake (O_{2 max}). Totest this hypothesis, we used the canine gastrocnemius muscle to studymaximal exercise in eight dogs at a normalP₅₀ (33.1 ± 0.4 Torr) and withthe O₂ dissociation curve shifted to the right by anallosteric modifier of hemoglobin (Hb) (methylpropionic acid, RSR-13;P₅₀ = 53.2 ± 5.0 Torr). Fourcontrol dogs were also studied before and after infusion of vehicle.O₂ (100%) was inspired duringexercise to maintain arterial saturation in both conditions. The musclewas surgically isolated and electrically stimulated (tetanic train: 0.2-ms stimuli for 200-ms duration at 50 Hz, once per s). Tomaintain O₂ delivery (pre-RSR-13 = 19.1 ± 2.9; RSR-13 = 19.6 ± 2.5 ml · 100 g¹ · min¹),the muscle was pump perfused. At a constantO₂ delivery, RSR-13 significantlyincreased percent O₂ extraction(pre-RSR-13 = 61 ± 4.0; RSR-13 = 75.5 ± 4.7) andmuscle O_{2 max}(pre-RSR-13 = 11.8 ± 2.1; RSR-13 = 14.2 ± 1.5 ml · 100 g¹ · min¹).This improvement inO_{2 max} with increasedP₅₀ demonstrates itsO₂ supply dependence whenP₅₀ is normal and the importance of O₂ diffusive transport tomuscle at maximal 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.     

Effect of increased Hb-O2 affinity on VO2max at constant O2 delivery in dog muscle in situ

We investigated the effect of increasing hemoglobin- (Hb) O2 affinity on muscle maximal O2 uptake (VO2max) while muscle blood flow, [Hb], HbO2 saturation, and thus O2 delivery (muscle blood flow X arterial O2 content) to the working muscle were kept unchanged from control. VO2max was measured in isolated in situ canine gastrocnemius working maximally (isometric tetanic contractions). The muscles were pump perfused, in alternating order, with either normal blood [O2 half-saturation pressure of hemoglobin (P50) = 32.1 +/- 0.5 (SE) Torr] or blood from dogs that had been fed sodium cyanate (150 mg.kg-1.day-1) for 3-4 wk (P50 = 23.2 +/- 0.9). In both conditions (n = 8) arterial PO2 was set at approximately 200 Torr to fully saturate arterial blood, which thereby produced the same arterial O2 contents, and muscle blood flow was set at 106 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. VO2max was 11.8 +/- 1.0 ml.min-1.100 g-1 when perfused with the normal blood (control) and was reduced by 17% to 9.8 +/- 0.7 ml.min-1.100 g-1 when perfused with the low-P50 blood (P less than 0.01). Mean muscle effluent venous PO2 was also significantly less (26 +/- 3 vs. 30 +/- 2 Torr; P less than 0.01) in the low-P50 condition, as was an estimate of the capillary driving pressure for O2 diffusion, the mean capillary PO2 (45 +/- 3 vs. 51 +/- 2 Torr). However, the estimated muscle O2 diffusing capacity was not different between conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

H2 oxidation,O2 uptake and CO2 fixation in hydrogen treated soils

In many legume nodules, the H₂ produced as a byproduct of N₂ fixation diffuses out of the nodule and is consumed by the soil. To study the fate of this H₂ in soil, a H₂ treatment system was developed that provided a 300 cm³ sample of a soil:silica sand (2:1) mixture with a H₂ exposure rate (147 nmol H₂ cm^–3hr^–1) similar to that calculated exist in soils located within 1–4 cm of nodules (30–254 nmol H₂ cm^–3hr^–1). After 3 weeks of H₂ pretreatment, the treated soils had a K_m and V_max for H₂ uptake (1028 ppm and 836 nmol cm^–3 hr^–1, respectively) much greater than that of control, air-treated soil (40.2 ppm and 4.35 nmol cm^–3 hr^–1, respectively). In the H₂ treated soils, O₂, CO₂ and H₂ exchange rates were measured simultaneously in the presence of various pH₂. With increasing pH₂, a 5-fold increase was observed in O₂ uptake, and CO₂ evolution declined such that net CO₂ fixation was observed in treatments of 680 ppm H₂ or more. At the H₂ exposure rate used to pretreat the soil, 60% of the electrons from H₂ were passed to O₂, and 40% were used to support CO₂ fixation. The effect of H₂ on the energy and C metabolism of soil may account for the well-known effect of legumes in promoting soil C deposition.