Skeletal muscle PO2 during hypoxemia and isovolemic anemia

We subjected anesthetized mechanically ventilated rabbits (n = 6) to sequential exchanges of blood for a 6% dextran solution and compared their responses with those obtained in a previous study on progressive hypoxemia (n = 7). Right atrial PO2 (PVO2)RA and hindlimb PO2 (PVO2)limb, measured at the level of the iliac bifurcation, were compared with tissue PO2 (PtiO2) histograms obtained with an array of surface microelectrodes placed over the biceps femoris muscle. Systemic O2 consumption (VO2) was measured with the expired gas method. Cardiac output and systemic O2 transport (TO2) were calculated. Six exchanges of blood for dextran produced decreases in hemoglobin from 10.8 +/- 0.4 to 2.7 +/- 0.2 g/dl (P less than 0.001). Critical TO2 (TO2crit), defined as the level of TO2 associated with initial decreases in control VO2, was similar for anemia and hypoxemia (40.5 +/- 5.6 and 40.1 +/- 5.3 ml.min-1.kg-1, respectively). At any given TO2 other than control TO2, the levels of (PVO2)RA and (PVO2)limb were greater in anemia than in hypoxemia (P less than 0.01), but the mean and the distribution of the PtiO2 histograms were similar in both conditions. Mean PtiO2 was significantly less than (PVO2)RA or (PVO2)limb, except for those values obtained during the control period. These results confirm our previous finding that PVO2 is not an accurate index of PtiO2 under conditions of tissue hypoxia. Furthermore, similar PtiO2 levels during anemia and hypoxemia suggest that VO2 is limited by decreases in O2 diffusion from the capillaries to the cells.     

Skeletal muscle energy metabolism during prolonged, fatiguing exercise.

A depletion of phosphocreatine (PCr), fall in the total adenine nucleotide pool (TAN = ATP + ADP + AMP), and increase in TAN degradation products inosine 5'-monophosphate (IMP) and hypoxanthine are observed at fatigue during prolonged exercise at 70% maximal O(2) uptake in untrained subjects [J. Baldwin, R. J. Snow, M. F. Carey, and M. A. Febbraio. Am. J. Physiol. 277 (Regulatory Integrative Comp. Physiol. 46): R295-R300, 1999]. The present study aimed to examine whether these metabolic changes are also prevalent when exercise is performed below the blood lactate threshold (LT). Six healthy, untrained humans exercised on a cycle ergometer to voluntary exhaustion at an intensity equivalent to 93 +/- 3% of LT ( approximately 65% peak O(2) uptake). Muscle biopsy samples were obtained at rest, at 10 min of exercise, approximately 40 min before fatigue (F-40 =143 +/- 13 min), and at fatigue (F = 186 +/- 31 min). Glycogen concentration progressively declined (P < 0.01) to very low levels at fatigue (28 +/- 6 mmol glucosyl U/kg dry wt). Despite this, PCr content was not different when F-40 was compared with F and was only reduced by 40% when F was compared with rest (52. 8 +/- 3.7 vs. 87.8 +/- 2.0 mmol/kg dry wt; P < 0.01). In addition, TAN concentration was not reduced, IMP did not increase significantly throughout exercise, and hypoxanthine was not detected in any muscle samples. A significant correlation (r = 0.95; P < 0. 05) was observed between exercise time and glycogen use, indicating that glycogen availability is a limiting factor during prolonged exercise below LT. However, because TAN was not reduced, PCr was not depleted, and no correlation was observed between glycogen content and IMP when glycogen stores were compromised, fatigue may be related to processes other than those involved in muscle high-energy phosphagen metabolism.     

Effect of flow on O2 consumption during progressive hypoxemia

Rabbit hindlimb preparations perfused with blood from donor rabbits were used to determine whether O2 consumption (VO2) during hypoxemia is limited by total O2 transport (TO2) or by capillary O2 driving pressure, as reflected by the venous PO2 (PVO2). The preparations were randomized into two groups: low flow (LF) and high flow (HF), perfused at 18 and 32 ml.min-1.kg of preparation wt-1, respectively. After a 1-h base-line period with arterial PO2 (PaO2) greater than 100 Torr, both groups were exposed to progressive decrements in PaO2 to less than 10 Torr. Sequential sets of arterial and venous blood gases were obtained, and VO2, TO2, and O2 extraction ratio (ERO2) were calculated. A plot of PVO2 vs. TO2 showed higher levels of PVO2 (P less than 0.05) in LF than HF, when compared at similar levels of TO2. Therefore the experimental protocol allowed the comparison of the separate effects of TO2 or PVO2 on VO2. Plotting VO2 as a function of TO2 revealed two distinct curves (P less than 0.05), with LF having a greater VO2 than HF at a given TO2. Conversely, a plot of VO2 as a function of PVO2 did not show a difference between the groups. The ERO2 of LF was greater than HF when compared at similar levels of TO2 (P less than 0.05). We conclude from these data that during progressive hypoxemia VO2 appears to be primarily limited by factors that determine capillary O2 diffusion. This conclusion supports the Kroghian theory of capillary O2 exchange.     

Increased hemoglobin O2 affinity does not improve O2 consumption in hypoxemia

We perfused an isolated rabbit hindlimb preparation with suspensions of human erythrocytes (RBC) having different O2 affinities. Our objective was to compare the effect of changes in P50, the PO2 at which hemoglobin is 50% saturated, on tissue O2 consumption during severe hypoxemia. A high-affinity (HA) group (n = 9) was perfused with RBC incubated in NaCNO (P50 = 21.4 +/- 1.9 Torr). This was compared with a low-affinity (LA) group (n = 9) perfused with rejuvenated RBC (P50 = 31.1 +/- 1.8 Torr). The arterial PO2 of the perfusate was decreased to approximately 24 Torr in both preparations. Perfusion flow and hemoglobin concentration were maintained constant. During hypoxemia arterial O2 saturation and total O2 transport (TO2) were greater in the HA than the LA group (P less than 0.05). O2 consumption and effluent venous PO2 decreased with hypoxemia in both groups to similar levels. Consequently, the LA group showed a greater O2 extraction ratio than the HA group (P less than 0.05). The ratio of phosphocreatine to inorganic phosphate, measured with 31P magnetic resonance spectroscopy, decreased at a comparable rate in both groups. As shown by a mathematical model of peripheral O2 transport, these experimental results can be explained on the basis of peripheral limitation to O2 diffusion. We conclude that increased hemoglobin affinity does not appreciably improve tissue oxygenation in hypoxemia, since the increase in TO2 is offset by diffusion limitation at the tissues.     

Skeletal muscle glutamine metabolism during sepsis in the rat

1. The effect of sepsis, induced by caecal ligation plus puncture (CLP) or endotoxin injection, on glutamine metabolism was studied in rat skeletal muscle. 2. The concentration of glutamine in muscle was decreased by CLP or after 24 or 48 hr after injection of endotoxin. However, the concentration was increased 3 hr after injection of endotoxin. 3. The plasma glutamine concentration was decreased by CLP, but it was unchanged after injection of endotoxin. 4. The rate of glutamine release from incubated stripped soleus muscles was increased in the muscles removed from animals subjected to CLP or from animals injected with endotoxin. 5. It is concluded that sepsis results in marked changes in skeletal muscle glutamine metabolism, which may be used as an early indicator of the septic state. During sepsis there is likely to be an increased demand for glutamine by the immune system, kidney and intestine. 6. This study provides evidence that during sepsis the rate of release of glutamine from the skeletal muscle per se is increased to a sufficient extent to satisfy this increased requirement.     

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.     

Skeletal muscle metabolism during exercise is influenced by heat acclimation

The influence of heat acclimation on skeletal muscle metabolism during submaximal exercise was studied in 13 healthy men. The subjects performed 30 min of cycle exercise (70% of individual maximal O2 uptake) in a cool [21 degrees C, 30% relative humidity (rh)] and a hot (49 degrees C, 20% rh) environment before and again after they were heat acclimated. Aerobic metabolic rate was lower (0.1 l X min-1; P less than 0.01) during exercise in the heat compared with the cool both before and after heat acclimation. Muscle and plasma lactate accumulation with exercise was greater (P less than 0.01) in the hot relative to the cool environment both before and after acclimation. Acclimation lowered (P less than 0.01) aerobic metabolic rate as well as muscle and plasma lactate accumulation in both environments. The amount of muscle glycogen utilized during exercise in the hot environment did not differ from that in the cool either before or after acclimation. These findings indicate that accumulation of muscle lactate is increased and aerobic metabolic rate is decreased during exercise in the heat before and after heat acclimation; increased muscle glycogen utilization does not account for the increased muscle lactate accumulation during exercise under extreme heat stress; and heat acclimation lowers the aerobic metabolic rate and muscle and blood lactate accumulation during exercise in a cool as well as a hot environment.     

Relationship of venous PO2 to muscle PO2 during hypoxemia

Anesthetized mechanically ventilated rabbits were subjected to progressive hypoxemia (n = 7) to determine the relationship of venous PO2 (PvO2) to skeletal muscle PO2 (PtiO2). Measures of arterial PO2 (PaO2), right atrial PO2 [(PvO2)RA], and hindlimb PO2 [(PvO2)limb], were obtained from the carotid artery, right atrium, and inferior vena cava, just above the level of the iliac bifurcation. Biceps femoris muscle PtiO2 was measured with a surface O2 microelectrode having eight measuring points. PaO2 was decreased from 90.3 +/- 5.4 to 26.8 +/- 0.8 Torr in five consecutive steps, followed by reoxygenation to 105.6 +/- 10.5 (SE) Torr. Measurements were obtained after each decrement in PaO2. A total of 128 measures of PtiO2 were obtained per experimental stage. The mean and distribution of the muscle PtiO2 histogram were determined. Measurements were compared with analysis of variance and the Newman-Keuls post hoc method. (PvO2)limb had similar values as the average muscle PtiO2 (PtiO2) for PaO2 values greater than 52.1 +/- 4.3 Torr, where (PvO2)limb became greater than PtiO2 (P less than 0.05). The lowest measures of (PvO2)limb and PtiO2 were 15.9 +/- 0.7 and 4.0 +/- 0.1 Torr, respectively (P less than 0.01). The PtiO2 histograms showed no evidence of increased microvascular heterogeneity with hypoxemia. We conclude that in hypoxemia PvO2 is greater than muscle PtiO2. This difference may be related to the establishment of significant physicochemical O2 gradients from erythrocyte to tissue cell.     

Skeletal muscle lipid metabolism with obesity

The objectives of this study were to 1). examine skeletal muscle fatty acid oxidation in individuals with varying degrees of adiposity and 2). determine the relationship between skeletal muscle fatty acid oxidation and the accumulation of long-chain fatty acyl-CoAs. Muscle was obtained from normal-weight [n = 8; body mass index (BMI) 23.8 +/- 0.58 kg/m(2)], overweight/obese (n = 8; BMI 30.2 +/- 0.81 kg/m(2)), and extremely obese (n = 8; BMI 53.8 +/- 3.5 kg/m(2)) females undergoing abdominal surgery. Skeletal muscle fatty acid oxidation was assessed in intact muscle strips. Long-chain fatty acyl-CoA concentrations were measured in a separate portion of the same muscle tissue in which fatty acid oxidation was determined. Palmitate oxidation was 58 and 83% lower in skeletal muscle from extremely obese (44.9 +/- 5.2 nmol x g(-1) x h(-1)) patients compared with normal-weight (71.0 +/- 5.0 nmol x g(-1) x h(-1)) and overweight/obese (82.2 +/- 8.7 nmol x g(-1) x h(-1)) patients, respectively. Palmitate oxidation was negatively (R = -0.44, P = 0.003) associated with BMI. Long-chain fatty acyl-CoA content was higher in both the overweight/obese and extremely obese patients compared with normal-weight patients, despite significantly lower fatty acid oxidation only in the extremely obese. No associations were observed between long-chain fatty acyl-CoA content and palmitate oxidation. These data suggest that there is a defect in skeletal muscle fatty acid oxidation with extreme obesity but not overweight/obesity and that the accumulation of intramyocellular long-chain fatty acyl-CoAs is not solely a result of reduced fatty acid oxidation.     

Skeletal muscle myosin heavy chain isoforms and energy metabolism after clenbuterol treatment in the rat

Prolonged treatment with the beta(2)-adrenoceptor agonist clenbuterol (1-2 mg. kg body mass(-1). day (-1)) is known to induce the hypertrophy of fast-contracting fibers and the conversion of slow- to fast-contracting fibers. We investigated the effects of administering a lower dose of clenbuterol (250 microgram. kg body mass(-1). day (-1)) on skeletal muscle myosin heavy chain (MyHC) protein isoform content and adenine nucleotide (ATP, ADP, and AMP) concentrations. Male Wistar rats were administered clenbuterol (n = 8) or saline (n = 6) subcutaneously for 8 wk, after which the extensor digitorum longus (EDL) and soleus muscles were removed. We demonstrated an increase of type IIa MyHC protein content in the soleus from approximately 0.5% in controls to approximately 18% after clenbuterol treatment (P < 0.05), which was accompanied by an increase in the total adenine nucleotide pool (TAN; approximately 19%, P < 0.05) and energy charge [E-C = (ATP + 0.5 ADP)/(ATP + ADP + AMP); approximately 4%; P < 0.05]. In the EDL, a reduction in the content of the less prevalent type I MyHC protein from approximately 3% in controls to 0% after clenbuterol treatment (P < 0.05) occurred without any alterations in TAN and E-C. These findings demonstrate that the phenotypic changes previously observed in slow muscle after clenbuterol administration at 1-2 mg. kg body mass(-1). day(-1) are also observed at a substantially lower dose and are paralleled by concomitant changes in cellular energy metabolism.     

Skeletal muscle oxidative metabolism in sedentary humans: 31P-MRS assessment of O2 supply and demand limitations.

Previously, it was demonstrated in exercise-trained humans that phosphocreatine (PCr) recovery is significantly altered by fraction of inspired O2 (FI(O2)), suggesting that in this population under normoxic conditions, O2 availability limits maximal oxidative rate. Haseler LJ, Hogan ML, and Richardson RS. J Appl Physiol 86: 2013-2018, 1999. To further elucidate these population-specific limitations to metabolic rate, we used 31P-magnetic resonance spectroscopy to study the exercising human gastrocnemius muscle under conditions of varied FI(O2) in sedentary subjects. To test the hypothesis that PCr recovery from submaximal exercise in sedentary subjects is not limited by O2 availability, but rather by their mitochondrial capacity, six sedentary subjects performed three bouts of 6-min steady-state submaximal plantar flexion exercise followed by 5 min of recovery while breathing three different FI(O2) (0.10, 0.21, and 1.00). PCr recovery time constants were significantly longer in hypoxia (47.0 +/- 3.2 s), but there was no difference between hyperoxia (31.8 +/- 1.9 s) and normoxia (30.0 +/- 2.1 s) (mean +/- SE). End-exercise pH was not significantly different across treatments. These results suggest that the maximal muscle oxidative rate of these sedentary subjects, unlike their exercise-trained counterparts, is limited by mitochondrial capacity and not O2 availability in normoxia. Additionally, the significant elongation of PCr recovery in these subjects in hypoxia illustrates the reliance on O2 supply at the other end of the O2 availability spectrum in both sedentary and active populations.     

Renal O2 consumption during progressive hemorrhage

Most mammalian tissues regulate O2 utilization such that O2 consumption (VO2) is relatively constant at O2 delivery (DO2) higher than a critical value (DO2c). We studied the relationship between VO2 and DO2 of kidney and whole body during graded progressive exsanguination. The relationship between whole body VO2 and DO2 was biphasic, and whole body VO2 decreased by 5.6 +/- 14.4% (P = NS) from the initial value to the value nearest whole body DO2c. Kidney DO2 decreased in direct proportion to whole body DO2 such that the average R2 value describing the linear regression of kidney DO2 vs. whole body DO2 was 0.94 +/- 0.02. The relationship between kidney, like whole body, VO2 and DO2 appeared biphasic; however, kidney VO2 decreased by 63.3 +/- 10.4% (P less than 0.0001) from the initial value to the value nearest kidney DO2c. Renal O2 extraction ratio was relatively constant over a wide range of kidney DO2, whereas whole body O2 extraction ratio increased progressively at all whole body DO2 values as whole body DO2 decreased. However, final values of O2 extraction ratio were indistinguishable for whole body (0.86 +/- 0.1) and kidney (0.86 +/- 0.06) (P = NS). We conclude that the pattern of kidney and whole body VO2 response to decreasing DO2 differs during hemorrhage, particularly in the range of DO2 normally associated with tissue wellness.     

Human skeletal muscle function and metabolism during intense exercise at high O2 and N2 pressures

The maximal contractile force (peak torque) of the quadriceps femoris was studied during 60 repeated unilateral dynamic knee extensions in nine subjects under three different conditions, viz., during air breathing at normal (1 ATA) and raised (6 ATA) ambient pressures and during O2 breathing at 1.3 ATA. In six subjects the electromyographic (EMG) activity of the working muscle was recorded. Muscle biopsies were obtained from the vastus lateralis before, immediately after, and 1 min after exercise. Tissue specimens were subsequently assayed for various muscle metabolites. Peak torque, as an average of the 60 knee extensions, was higher (P less than 0.05) at 1.3 ATA than at 6 or 1 ATA. Peak torque of the exercising muscle declined more rapidly at 1 ATA than at 1.3 ATA, differing in the final 24 contractions by 14%. At 6 ATA peak torque of the initial 12 contractions was 6% lower (P less than 0.05) than at 1 ATA but equaled 1-ATA values in the latter third of the exercise bout. Although the EMG activity at 1 ATA increased relative to that at 6 ATA as exercise proceeded, the rate of force decline was greater at 1 ATA. Despite greater total work produced at 1.3 ATA than at 1 ATA, the metabolic response to exercise was not substantially altered at increased O2 pressure. However, the restitution rate of energy-rich phosphagens and the elimination of lactate during recovery were greater (P less than 0.05) at 1.3 ATA. These results suggest that hyperoxia may enhance the rate of energy release, whereas high N2 pressure and/or high hydrostatic pressure seem to interfere with neuromuscular activity.     

Skeletal muscle metabolism during short-term, high-intensity exercise in prepubertal and pubertal girls.

To test the hypothesis that glycolytic metabolism in muscle is attenuated in prepubertal children, (31)P-magnetic resonance spectroscopy was used to determine calf muscle intracellular pH (pH(i)) in nine prepubertal (Pre) and nine pubertal female swimmers (Pub). Maximal plantar flexion work capacity (100% MWC) was established by using a graded exercise test. Between 5 and 10 days later, calf muscle images (magnetic resonance imaging) and phosphorus spectra were acquired at rest, during 2 min of light exercise (40% MWC), and during 2 min of supramaximal exercise (140% MWC) in a 3.0-T NMR system. End-exercise pH(i) was 6.66 +/- 0.11 and 6.76 +/- 0.17 for Pub and Pre, respectively. No significant differences in the mean values for pH(i) or the P(i)-to-phosphocreatine ratio were observed between groups during the protocol; however, an interaction effect was found for the P(i)-to-phosphocreatine ratio during the supramaximal exercise challenge. Cross-sectional area of gastrocnemius was 15.12 +/- 0.46 and 9.37 +/- 0.37 cm(2) for Pub and Pre, respectively (P < 0.05). Differences in muscle size must be considered when interpreting the unlocalized magnetic resonance spectroscopy data. These results suggest that glycolytic metabolism in physically active children is not maturity dependent.     

Bioenergetics of rabbit skeletal muscle during hypoxemia and ischemia

A blood-perfused rabbit hindlimb preparation was exposed to total ischemia (n = 4) or to severe hypoxemia (n = 4) where arterial PO2 was 5 +/- 2 (SE) Torr. O2 consumption (VO2), O2 transport (TO2), venous PO2 (PVO2), venous lactate concentration, and venous glucose concentration were measured. The relative concentration of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), and intracellular pH (pHi) were monitored with 31P magnetic resonance spectroscopy. PCr/Pi decreased with the onset of ischemia or hypoxemia. The preparation was reoxygenated and allowed to recover for 30 min once PCr/Pi was less than 1.0. The periods of hypoxemia and ischemia lasted 56.0 +/- 10.0 and 63.8 +/- 2.5 min, respectively (NS). During ischemia PCr decreased and Pi increased compared with control (P less than 0.05) but returned to control with reperfusion. With hypoxemia PCr also decreased and Pi increased with respect to control (P less than 0.01) but did not recover with reoxygenation. VO2 and PVO2 in both groups returned to control during recovery. ATP did not change with ischemia but decreased with hypoxemia (P less than 0.05). Venous lactate concentration did not change with ischemia but increased with hypoxemia (P less than 0.05) and continued to rise during recovery. During recovery pHi decreased in the hypoxemic group (P less than 0.05) but not in the ischemic group. These data show that, under the conditions tested, rabbit skeletal muscle does not resynthesize PCr after a severe hypoxemic episode. Furthermore it appears that VO2 and PVO2 fail to portray the true state of cellular bioenergetics after a severe hypotemic insult.     

Nitric oxide regulation of myocardial O2 consumption and HEP metabolism

NO and O(2) compete at cytochrome-c oxidase, thus potentially allowing NO to modulate mitochondrial respiration. We previously observed a decrease of myocardial phosphocreatine (PCr)/ATP during very high cardiac work states, corresponding to an increase in cytosolic free ADP. This study tested the hypothesis that NO inhibition of respiration contributes to this increase of ADP. Infusion of dobutamine + dopamine (DbDp, each 20 microg.kg(-1).min(-1) iv) to more than double myocardial oxygen consumption (MVo(2)) in open-chest dogs caused a decrease of myocardial PCr/ATP measured with (31)P NMR from 2.04 +/- 0.09 to 1.85 +/- 0.08 (P < 0.05). Inhibition of NO synthesis with N(omega)-nitro-L-arginine (L-NNA), while catecholamine infusion continued, caused PCr/ATP to increase to the control value. In a second group of animals, L-NNA administered before catecholamine stimulation (reverse intervention of the first group) increased PCr/ATP during basal conditions. In these animals L-NNA did not prevent a decrease of PCr/ATP at the high cardiac work state but, relative to MVo(2), PCr/ATP was significantly higher after L-NNA. In a third group of animals, pharmacological coronary vasodilation with carbochromen was used to prevent changes in coronary flow that might alter endothelial NO production. In these animals L-NNA again restored depressed myocardial PCr/ATP during catecholamine infusion. The finding that inhibition of NO production increased PCr/ATP suggests that during very high work states NO inhibition of mitochondrial respiration requires ADP to increase to drive oxidative phosphorylation.     

Skeletal muscle metabolism in physiology and in cancer disease

Skeletal muscle is a tissue of high demand and it accounts for most of daily energy consumption. The classical concept of energy metabolism in skeletal muscle has been profoundly modified on the basis of studies showing the influence of additional factors (i.e., uncoupling proteins (UCPs) and peroxisome proliferator activated receptors (PPARs)) controlling parameters, such as substrate availability, cellular enzymes, carrier proteins, and proton leak, able to affect glycolysis, nutrient oxidation, and protein degradation. This extremely balanced system is greatly altered by cancer disease that can induce muscle cachexia with significant deleterious consequences and results in muscle wasting and weakness, delaying or preventing ambulation, and rehabilitation in catabolic patients.     

Ventilatory muscle recruitment in exercise with O2 in obstructed patients with mild hypoxemia

Respiratory muscle dysfunction limits exercise endurance in severe chronic airflow obstruction (CAO). To investigate whether inspiring O2 alters ventilatory muscle recruitment and improves exercise endurance, we recorded pleural (Ppl) and gastric (Pga) pressures while breathing air or 30% O2 during leg cycling in six patients with severe CAO, mild hypoxemia, and minimal arterial O2 desaturation with exercise. At rest, mean (+/- SD) transdiaphragmatic pressure (Pdi) was lower inspiring 30% O2 compared with air (23 +/- 4 vs. 26 +/- 7 cmH2O, P less than 0.05), but the pattern of Ppl and Pga contraction was identical while breathing either gas mixture. Maximal transdiaphragmatic pressure was similar breathing air or 30% O2 (84 +/- 30 vs. 77 +/- 30 cmH2O). During exercise, Pdi increased similarly while breathing air or 30% O2, but the latter was associated with a significant increase in peak inspiratory Pga and decreases in peak inspiratory Ppl and expiratory Pga. In five out of six patients, exercise endurance increased with O2 (671 +/- 365 vs. 362 +/- 227 s, P less than 0.05). We conclude that exercise with O2 alters ventilatory muscle recruitment and increases exercise endurance. During exercise inspiring O2, the diaphragm performs more ventilatory work which may prevent overloading the accessory muscles of respiration.