Hypohydration affects forearm vascular conductance independent of heart rate during exercise.

Elevated body core temperature stimulates cutaneous vasodilation, which can be modified by nonthermal factors. To test whether hypohydration affects forearm vascular conductance discretely from relative alterations in heart rate (HR), eight trained cyclists exercised progressively for 20 min each at 60, 120, and 180 W [approximately 22, 37, and 55% of maximal cycling O2 consumption (VO2peak), respectively] in a warm humid environment (dry bulb temperature 30 degrees C; wet bulb temperature 24 degrees C). Esophageal temperature and forearm blood flow were measured every 30 s, and mean arterial pressure and HR were measured at rest and during each exercise intensity (minutes 15, 35, and 55). In the hypovolemic (HP) compared with the euvolemic (EU) state, blood volume was contracted by 24-h fluid restriction an average of 510 ml, and this difference was sustained throughout exercise. The esophageal temperature and HR responses were similar between EU and HP states at 60 and 120 W but were significantly (P < 0.05) higher in HP by the end of 180 W. In contrast, the forearm blood flow response was significantly (P < 0.05) depressed during exercise at 120 and 180 W in HP, whereas mean arterial pressure remained similar between conditions. When body core temperature is elevated in a hypohydrated state, forearm vascular conductance is reduced at exercise intensities of approximately 37% VO2peak, which is independent of relative changes in HR. These findings are consistent with the notion that during exercise an attenuated cutaneous vasodilation is elicited by alterations in regionalized sympathetic outflow, which is unaccompanied by activation of cardiac pacemaker cells.     

A 31P-NMR study of tissue respiration in working dog muscle during reduced O2 delivery conditions.

To investigate the role of tissue oxygenation as one of the control factors regulating tissue respiration, 31P-nuclear magnetic resonance spectroscopy (31P-NMR) was used to estimate muscle metabolites in isolated working muscle during varied tissue oxygenation conditions. O2 delivery (muscle blood flow x arterial O2 content) was varied to isolated in situ working dog gastrocnemius (n = 6) by decreases in arterial PO2 (hypoxemia; H) and by decreases in muscle blood flow (ischemia; I). O2 uptake (VO2) was measured at rest and during work at two or three stimulation intensities (isometric twitch contractions at 3, 5, and occasionally 7 Hz) during three separate conditions: normal O2 delivery (C) and reduced O2 delivery during H and I, with blood flow controlled by pump perfusion. Biochemical metabolites were measured during the last 2 min of each 3-min work period by use of 31P-NMR, and arterial and venous blood samples were drawn and muscle blood flow measured during the last 30 s of each work period. Muscle [ATP] did not fall below resting values at any work intensity, even during O2-limited highly fatiguing work, and was never different among the three conditions. Muscle O2 delivery and VO2 were significantly less (P < 0.05) at the highest work intensities for both I and H than for C but were not different between H and I. As VO2 increased with stimulation intensity, a larger change in any of the proposed regulators of tissue respiration (ADP, P(i), ATP/ADP.P(i), and phosphocreatine) was required during H and I than during C to elicit a given VO2, but requirements were similar for H and I.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypoxic ventilatory response during light and dark periods and the involvement of histamine H1 receptor in mice

Ventilation oscillates throughout a day in parallel with oscillations in metabolic rate. Histamine affects ventilation and the balance of the energy metabolism via H1 receptors in the brain. We tested the hypothesis that the ventilatory response to hypoxia varies between light and dark periods and that histamine H1 receptors are required for the circadian variation, using wild-type (WT) and histamine H1 receptor knockout (H1RKO) mice. Mice were exposed to hypoxic gas (7% O(2) + 3% CO(2) in N(2)) during light and dark periods. Ventilation initially increased and then declined. In WT mice, minute ventilation (.Ve) during hypoxia was higher in the dark period than in the light period, which was an upward shift along with the baseline ventilation. Hypoxia decreased the metabolic rate, whereas O2 consumption (.VO(2)) and CO(2) excretion were higher in the dark period than in the light period. However, in H1RKO mice, changes in Ve during hypoxia between light and dark periods were minimal, because .Ve was increased relative to .VO(2), particularly in the light period. In H1RKO mice, the HCO(3)(-) concentration and base excess values were increased in arterial blood, and the level of ketone bodies was increased in the serum, indicating that metabolic acidosis occurred. Respiratory compensation takes part in the .Ve increase relative to .VO(2) during hypoxia. These results suggested that changes in .Ve during hypoxia vary between light and dark periods and that H1 receptors play a role in circadian variation in .Ve through control of the acid-base status and metabolism in mice.     

Role of hemoglobin P50 in O2 transport during normoxic and hypoxic exercise in the dog

High hemoglobin affinity for O2 [low PO2 at 50% saturation of hemoglobin (P50)] could degrade exercise performance in normoxia by lowering mean tissue PO2 but could enhance O2 transport in hypoxic exercise by increasing arterial O2 saturation. We measured O2 transport at rest and at graded levels of steady-state exercise in tracheostomized dogs with normal P50 (28.8 +/- 1.8 Torr) and again after P50 was lowered (19.5 +/- 0.7 Torr) by sodium cyanate infusions. Measurements were made during ventilation with room air (RA), 12% O2 in N2, or 10% O2 in N2. Cardiac output (QT) as a function of O2 consumption (VO2) was not altered by low P50 at any inspired O2 fraction (P greater than 0.05). With RA exercise, arterial content (CaO2) and O2 delivery (QT X CaO2) were unchanged at low P50, whereas mixed venous PO2 was reduced at each level of VO2. With exercise in hypoxia, CaO2 and O2 delivery were significantly improved at low P50 (P less than 0.05). Mixed venous PO2 was lower than control during 12% O2 (P less than 0.05) but not different from control during 10% O2 exercise at low P50. Despite a presumed decrease in tissue PO2 during RA and 12% O2 exercise, exercise performance and base excess decline were not significantly worse than control levels. We conclude that, in canine steady-state exercise, hemoglobin P50 is not an important determinant of tissue O2-extraction capacity during normoxia or moderate hypoxia. In extreme hypoxia, low P50 may help to maintain tissue PO2 by enhancing systemic O2 delivery at each level of QT.     

Effects of training on muscle O2 transport at VO2max.

To quantify the relative contributions of convective and peripheral diffusive components of O2 transport to the increase in leg O2 uptake (VO2leg) at maximum O2 uptake (VO2max) after 9 wk of endurance training, 12 sedentary subjects (age 21.8 +/- 3.4 yr, VO2max 36.9 +/- 5.9 ml.min-1.kg-1) were studied. VO2max, leg blood flow (Qleg), and arterial and femoral venous PO2, and thus VO2leg, were measured while the subjects breathed room air, 15% O2, and 12% O2. The sequence of the three inspirates was balanced. After training, VO2max and VO2leg increased at each inspired O2 concentration [FIO2; mean over the 3 FIO2 values 25.2 +/- 17.8 and 36.5 +/- 33% (SD), respectively]. Before training, VO2leg and mean capillary PO2 were linearly related through the origin during hypoxia but not during room air breathing, suggesting that, at 21% O2, VO2max was not limited by O2 supply. After training, VO2leg and mean capillary PO2 at each FIO2 fell along a straight line with zero intercept, just as in athletes (Roca et al. J. Appl. Physiol. 67: 291-299, 1989). Calculated muscle O2 diffusing capacity (DO2) rose 34% while Qleg increased 19%. The relatively greater rise in DO2 increased the DO2/Qleg, which led to 9.9% greater O2 extraction. By numerical analysis, the increase in Qleg alone (constant DO2) would have raised VO2leg by 35 ml/min (mean), but that of DO2 (constant Qleg) would have increased VO2leg by 85 ml/min, more than twice as much. The sum of these individual effects (120 ml/min) was less (P = 0.013) than the observed rise of 164 ml/min (mean). This synergism (explained by the increase in DO2/Qleg) seems to be an important contribution to increases in VO2max with training.     

Relationships of femoral venous [K+], PO2, osmolality, and [orthophosphate) with heart rate, ventilation, and leg blood flow during bicycle exercise in athletes and non-athletes.

The relationship of femoral venous [K+], [H+], osmolality (OSM), PO2, and [inorganic phosphate] ([Pi]) with heart rate (HR), ventilation (VE), and calculated leg blood flow (Q) were investigated during bicycle exercise in endurance trained (TR) and untrained (UT) test subjects. At a given VO2 the increases of [K+], OSM, [Pi] and the decrease of PO2 were significantly lower in TR than in UT. In the same proportion the increases of HR, VE, and Q were diminished. Thus in TR and UT identical and highly significantly correlated regression lines of [K+], [H+], OSM, [Pi] and PO2 with HR, VE, and Q were obtained. These constituents changed in the same proportion as the relative VO2 in TR and UT. No relationships with [Na+], [Ca++], and [ Mg++] were found. By means of a multiple regression analysis the partial influence of K+, H+, OSM, PO2, and Pi upon the total change of HR, VE and Q was estimated to compare with data from infusion experiments. The findings were discussed in view of the hypothesis that these candidates may provide linkage between metabolic events, circulatory, and ventilatory adjustments during work.     

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.     

Immediate effects of cigarette smoking on cardiorespiratory responses to exercise

To determine the acute action of cigarette smoking on cardiorespiratory function under stress, the immediate effects of cigarette smoking on the ventilatory, gas exchange, and cardiovascular responses to exercise were studied in nine healthy male subjects. Each subject performed an incremental exercise test to exhaustion on two separate days, one without smoking (control) and one after smoking 3 cigarettes/h for 5 h. The order of the two tests was randomized. Arterial blood gases and pH were measured during rest and all levels of exercise; CO blood levels confirmed the absorption of cigarette smoke. In addition, minute ventilation (VE), end-tidal PCO2 and PO2, O2 uptake (VO2), CO2 production, directly measured blood pressure, electrocardiogram, and heart rate (HR) were recorded every 30 s. The dead space-to-tidal volume ratio (VD/VT), maximal aerobic capacity (VO2max), and anaerobic threshold (AT) were determined from the gas exchange data. Cigarette smoking resulted in a significantly lower VO2max, AT, and VO2/HR (O2 pulse) and a significantly higher HR, pulse-pressure product, and pulse pressure (P less than 0.05) compared with the control. Additionally, a trend toward a higher VD/VT and arterial-end-tidal PCO2 difference was found during exercise after smoking. We conclude that cigarette smoking causes immediate detrimental effects on cardiovascular function during exercise, including tachycardia, increased pulse-pressure product, and impaired O2 delivery. The acute effects on respiratory function were less striking and primarily limited to abnormalities reflecting ventilation-perfusion mismatching.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Cellular PO2 as a determinant of maximal mitochondrial O(2) consumption in trained human skeletal muscle.

Previously, by measuring myoglobin-associated PO(2) (P(Mb)O(2)) during maximal exercise, we have demonstrated that 1) intracellular PO(2) is 10-fold less than calculated mean capillary PO(2) and 2) intracellular PO(2) and maximum O(2) uptake (VO(2 max)) fall proportionately in hypoxia. To further elucidate this relationship, five trained subjects performed maximum knee-extensor exercise under conditions of normoxia (21% O(2)), hypoxia (12% O(2)), and hyperoxia (100% O(2)) in balanced order. Quadriceps O(2) uptake (VO(2)) was calculated from arterial and venous blood O(2) concentrations and thermodilution blood flow measurements. Magnetic resonance spectroscopy was used to determine myoglobin desaturation, and an O(2) half-saturation pressure of 3.2 Torr was used to calculate P(Mb)O(2) from saturation. Skeletal muscle VO(2 max) at 12, 21, and 100% O(2) was 0.86 +/- 0.1, 1.08 +/- 0.2, and 1.28 +/- 0.2 ml. min(-1). ml(-1), respectively. The 100% O(2) values approached twice that previously reported in human skeletal muscle. P(Mb)O(2) values were 2.3 +/- 0.5, 3.0 +/- 0.7, and 4.1 +/- 0.7 Torr while the subjects breathed 12, 21, and 100% O(2), respectively. From 12 to 21% O(2), VO(2) and P(Mb)O(2) were again proportionately related. However, 100% O(2) increased VO(2 max) relatively less than P(Mb)O(2), suggesting an approach to maximal mitochondrial capacity with 100% O(2). These data 1) again demonstrate very low cytoplasmic PO(2) at VO(2 max), 2) are consistent with supply limitation of VO(2 max) of trained skeletal muscle, even in hyperoxia, and 3) reveal a disproportionate increase in intracellular PO(2) in hyperoxia, which may be interpreted as evidence that, in trained skeletal muscle, very high mitochondrial metabolic limits to muscle VO(2) are being approached.     

Seizure-associated pulmonary edema and cerebral oxygenation in the rat

Cerebral partial pressure of O2 (PO2), relative changes in the ratio of reduced/oxidized cytochrome aa3, blood flow, and the arteriovenous difference in O2 content were measured during seizures with and without pulmonary edema. Seizures were induced with bicuculline (0.2-1.2 mg/kg iv) in rats anesthetized with 70% N2O and paralyzed with curare. Briefer seizures were accompanied by increased cerebral PO2 and increased oxidation of cytochrome aa3. Lung water content and arterial O2 partial pressure (PaO2) remained normal. Longer duration seizures were also accompanied initially by increases in cerebral oxygenation. Within minutes, however, PaO2 fell from a mean of 118 to 51 mmHg, and lung water content increased from 76.2 to 83.6%. Cerebral PO2 fell but most often rose back to or above control levels, while cytochrome aa3 became markedly reduced. Simultaneously, cerebral blood flow increased more than 300% above preseizure values and O2 delivery increased more than O2 consumption. The reductive shift of cytochrome aa3 was greater than that produced by lowering PaO2 to equivalent values in seizure-free rats. The reductive shift of cytochrome aa3, despite increased O2 delivery, may be indicative of derangements in cerebral O2 diffusion or energy metabolism.     

Influence of inhaled nitric oxide on gas exchange during normoxic and hypoxic exercise in highly trained cyclists.

This study tested the effects of inhaled nitric oxide [NO; 20 parts per million (ppm)] during normoxic and hypoxic (fraction of inspired O(2) = 14%) exercise on gas exchange in athletes with exercise-induced hypoxemia. Trained male cyclists (n = 7) performed two cycle tests to exhaustion to determine maximal O(2) consumption (VO(2 max)) and arterial oxyhemoglobin saturation (Sa(O(2)), Ohmeda Biox ear oximeter) under normoxic (VO(2 max) = 4.88 +/- 0.43 l/min and Sa(O(2)) = 90.2 +/- 0.9, means +/- SD) and hypoxic (VO(2 max) = 4.24 +/- 0.49 l/min and Sa(O(2)) = 75.5 +/- 4.5) conditions. On a third occasion, subjects performed four 5-min cycle tests, each separated by 1 h at their respective VO(2 max), under randomly assigned conditions: normoxia (N), normoxia + NO (N/NO), hypoxia (H), and hypoxia + NO (H/NO). Gas exchange, heart rate, and metabolic parameters were determined during each condition. Arterial blood was drawn at rest and at each minute of the 5-min test. Arterial PO(2) (Pa(O(2))), arterial PCO(2), and Sa(O(2)) were determined, and the alveolar-arterial difference for PO(2) (A-aDO(2)) was calculated. Measurements of Pa(O(2)) and Sa(O(2)) were significantly lower and A-aDO(2) was widened during exercise compared with rest for all conditions (P < 0.05). No significant differences were detected between N and N/NO or between H and H/NO for Pa(O(2)), Sa(O(2)) and A-aDO(2) (P > 0.05). We conclude that inhalation of 20 ppm NO during normoxic and hypoxic exercise has no effect on gas exchange in highly trained cyclists.     

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.     

Tissue temperature profile in the human forearm during thermal stress at thermal stability.

The purpose of the present study was to investigate the effect of a range of water temperatures (Tw from 15 to 36 degrees C) on the tissue temperature profile of the resting human forearm at thermal stability. Tissue temperature (Tti) was continuously monitored by a calibrated multicouple probe during 3 h of immersion of the forearm. The probe was implanted approximately 9 cm distal from the olecranon process along the ulnar ridge. Tti was measured every 5 mm, from the longitudinal axis of the forearm (determined from computed tomography scanning) to the skin surface. Along with Tti, skin temperature (Tsk), rectal temperature (Tre), and blood flow were measured during the immersions. For all temperature conditions, the temperature profile inside the limb was linear as a function of the radial distance from the forearm axis (P less than 0.001). Temperature gradient measured in the forearm ranged from 0.2 +/- 0.1 degrees C C cm (Tw = 36 degrees C) to 2.3 +/- 0.5 degrees C cm (Tw = 15 degrees C). The maximal Tti was measured in all cases at the longitudinal axis of the forearm and was in all experimental conditions lower than Tre. On immersion at Tw less than 36 degrees C, the whole forearm can be considered to be part of the shell of the body. With these experimental data, mathematical equations were developed to predict, with an accuracy of at least 0.6 degrees C, the Tti at any depth inside the forearm at steady state during thermal stress.(ABSTRACT TRUNCATED AT 250 WORDS)     

Establishing predictive indicators for the status of loaded soft tissues.

Two complementary techniques were employed to assess the soft tissue response to applied pressure. The noninvasive methods involve the simultaneous measurement of the local tensions of oxygen and carbon dioxide (tcPO2 and tcPCO2) and the collection and subsequent analysis of sweat collected from the sacrum, a common site for the development of pressure sores. All tests were performed on able-bodied subjects. Results have indicated that oxygen levels (tcPO2) were lowered in soft tissues subjected to applied pressures of between 40 (5.3 kPa) and 120 mmHg (16.0 kPa). At the higher pressures, this decrease was generally associated with an increase in carbon dioxide levels (tcPCO2) well above the normal basal levels of 45 mmHg (6 kPa). There were also considerable increases, in some cases up to twofold, in the concentrations of both sweat lactate and urea at the loaded site compared with the unloaded control. By comparing selected parameters, a threshold value for loaded tcPO2 was identified, representing a reduction of ~60% from unloaded values. Above this threshold, there was a significant relationship between this parameter and the loaded/unloaded concentration ratios for both sweat metabolites. These parameters may prove useful in identifying those subjects whose soft tissue may be compromised during periods of pressure ischemia.     

Forearm temperature profile during the transient phase of thermal stress.

The transient temperature response of the resting human forearm immersed in water at temperatures (Tw) ranging from 15 to 36 degrees C was investigated. Tissue temperature (Tt) was continuously monitored by a calibrated multicouple probe during the 3-h immersions. Tt was measured every 5 mm, from the longitudinal axis of the forearm to the skin surface. Skin temperature, rectal temperature, and blood flow (Q) were also measured during the immersions. The maximum rate of change of the forearm mean tissue temperature (Tt, max) occurred during the first 5 min of the immersion. Tt, max was linearly dependent on Tw (P less than 0.001), with mean values (SEM) ranging from -0.8 (0.1) degrees C.min-1 at 15 degrees C to 0.2 (0.1) degrees C.min-1 at 36 degrees C. The maximum rate of change of compartment mean temperature was dependent (P less than 0.001) on the radial distance from the longitudinal axis of the forearm. The half-time for thermal steady state of the forearm mean tissue temperature was linearly dependent on Tw between 30 and 36 degrees C (P less than 0.01), with mean values (SEM) ranging from 15.6 (0.6) min at 30 degrees C to 9.7 (1.2) min at 36 degrees C and not different between 15 and 30 degrees C, averaging 16.2 (0.6) min. There was a significant linear relationship between the half-time for thermal steady-state of the compartment mean temperature and the radial distance from the longitudinal axis of the forearm for each value of Tw tested (P less than 0.001). The data of the present study suggest that the forearm Q is an important determinant of the transient thermal response of the forearm tissue during thermal stress.     

Physiology of hibernation in Rana pipiens: metabolic rate, critical oxygen tension, and the effects of hypoxia on several plasma variables

Rates of O(2) consumption (.VO(2)) were determined for adult northern leopard frogs (Rana pipiens) submerged at 3 degrees C at water PO(2)s (P(w)O(2)) ranging from 0-160 mmHg. The critical O(2) tension (P(c)) was 36.4 mmHg. Hematocrit and blood levels of PO(2), glucose, lactate, pH, [Na(+)], [K(+)], and osmolality were determined for frogs submerged for two days. Above a P(w)O(2) of 50 mmHg, blood PO(2) ranged from 1-7 mmHg, which was sufficient to allow the frogs to function entirely aerobically. Plasma [lactate] increased as P(w)O(2) fell below 50 mmHg, the increase preceding significant changes in any other variable, and apparently preceding a fall in .VO(2). Most other variables showed little or no change from those of air-breathing control animals, even during anoxia. We present an analysis of the importance of a large decrease in P(c) in permitting frogs to successfully overwinter in icebound ponds and of the factors that contribute to that decrease.     

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.     

Metabolic and cardiovascular adjustment to arm training

Maximal and submaximal metabolic and cardiovascular measures and work capacity were studied in control (n = 7) and experimental (n = 9) subjects (S's) during arm work prior to and following 10 wk of interval arm training. These measures were oxygen uptake (VO2), minute ventilation (VE), heart rate (HR), respiratory exchange ratio (R), cardiac output (Q), stroke volume (SV), and arteriovenous oxygen difference ((a--v)O2 diff). In addition, maximal oxygen uptake (VO2max) was measured in both groups during treadmill running. Experimental S's showed significant increases (P less than 0.01) in peak VO2 (438 ml.min-1), max VE (17.7 l.min-1), max (a--v)O2 diff (20.8 ml.l-1), and work time (9.2 min) during arm ergometry, while maximum values of Q, SV, HR, and R remained unchanged. In addition, submaximal heart rates were significantly lower during arm ergometry after training. VO2max during treadmill running remained essentially unchanged. No changes in metabolic and physiological measures were noted for the controls after the 10-wk training period. The results support the concept of training specificity for VO2max, and indicate that the improvement in peak VO2 in arm ergometry reflects enhanced oxygen utilization due to an expanded (a--v)O2 diff.     

Muscle perfusion and oxygenation during local hyperoxia

Ventilation with O2 was previously shown to decrease whole-body and hindlimb muscle O2 uptake (VO2) in anesthetized dogs, particularly during anemia. To determine whether this was a purely local effect of hyperoxia (HiOx), we pump perfused isolated dog hindlimb muscles with autologous blood made hyperoxic (PO2 greater than 500 Torr) in a membrane oxygenator while the animals were ventilated with room air. Both constant-flow and constant-pressure protocols were used, and half the dogs were made anemic by exchange transfusion of dextran to hematocrit (Hct) approximately 15%. Thus there were four groups of n = 6 dogs each. A 30-min period of HiOx was preceded and followed by similar periods of perfusion with normoxic blood. In HiOx all four groups showed increased leg hindrance, increased leg venous PO2, and no significant changes in leg O2 inflow. Limb blood flow and VO2 decreased approximately 20% in HiOx with constant-pressure perfusion, regardless of Hct. In the constant-flow protocol, leg VO2 in HiOx was maintained by the anemic animals and actually increased in the normocythemic group. We conclude that HiOx directly affected vascular smooth muscle to cause flow restriction and maldistribution. Constant flow offset these effects, but the increased limb VO2 may have been a toxic effect. Anemia appeared to exaggerate the microcirculatory maldistribution caused by HiOx.