Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology

Lung impedance was measured from 0.01 to 0.1 Hz in six healthy adults by superimposing small-amplitude forced oscillations on spontaneous breathing. Measurements were made with an almost constant-volume input (160-180 ml) or with an almost constant-flow input (20-30 ml.s-1). No significant difference was found between the two conditions. Lung resistance (RL) sharply decreased from 0.97 kPa.l-1.s at 0.01 Hz to 0.27 kPa.l-1.s at 0.03 Hz and then mildly to 0.23 kPa.l-1.s at 0.1 Hz. Lung effective compliance (CL) decreased slightly and regularly from 0.01 Hz (2.38 l.kPa-1) to 0.1 Hz (1.93 l.kPa-1). The data were analyzed using a linear viscoelastic model adapted from Hildebrandt (J. Appl. Physiol. 28:365-372, 1970) and complemented by a Newtonian resistance (R): RL = R + B/(9.2f); CL = 1/(A + 0.25B + B.log2 pi f), where f is the frequency and B/A is an index of lung tissue viscoelasticity. A good fit was generally obtained, with an average difference of 10% between the observed and predicted values. The ratio B/A was not affected by the breathing and was 10.6 and 13.6% in the constant-volume and constant-flow conditions, respectively, which agrees with Hildebrandt's observations in isolated cat lungs. R was systematically larger than the plethysmographic airway resistance, suggesting that lung tissue resistance might also include a Newtonian component.

We investigated the rheological properties of living human airway smooth muscle cells in culture and monitored the changes in rheological properties induced by exogenous stimuli. We oscillated small magnetic microbeads bound specifically to integrin receptors and computed the storage modulus (G') and loss modulus (G") from the applied torque and the resulting rotational motion of the beads as determined from their remanent magnetic field. Under baseline conditions, G' increased weakly with frequency, whereas G" was independent of the frequency. The cell was predominantly elastic, with the ratio of G" to G' (defined as eta) being approximately 0. 35 at all frequencies. G' and G" increased together after contractile activation and decreased together after deactivation, whereas eta remained unaltered in each case. Thus elastic and dissipative stresses were coupled during changes in contractile activation. G' and G" decreased with disruption of the actin fibers by cytochalasin D, but eta increased. These results imply that the mechanisms for frictional energy loss and elastic energy storage in the living cell are coupled and reside within the cytoskeleton.

It has been reported (J. Clin. Invest. 57: 301-307, 1976) that inhalation of nitrogen dioxide (NO2) will enhance the bronchial reactivity of asthmatics. This study was designed to evaluate the respiratory effect of a 1-h exposure of normal subjects and of atopic asthmatics to 0.1 parts per million (ppm) NO2. Fifteen normal and 15 asthmatic subjects were exposed to air and to NO2 in a randomized double-blind crossover design. Exposure to either atmosphere was bracketed by bronchial inhalation challenge using aerosolized metacholine chloride solutions. Plethysmographic measurements of specific airway resistance (sRaw) and the forced random noise impedance spectrum (5-30 Hz) were obtained immediately after each methacholine dose. Following acute exposure to NO2, there was a slight but not significant increase in mean base-line sRaw in both normals and asthmatics. The overall base-line resistive properties of the respiratory system determined by forced random noise excitation were not significantly affected by NO2 inhalation either. Finally, there was no change in bronchial response to methacholine challenge in either group. These findings indicate that 0.1 ppm NO2 exposure for 1 h without exercise had no demonstrable airways effects in either young atopic asthmatics with mild disease or young normal subjects.

Pressure-volume curves were obtained from excised left lungs of goats at 4, 24, and 48 h after tracheal instillation of 2.5 ml/kg of 0.1 N HCl. Air total lung capacity (TLC) at transpulmonary pressure (PL) = 35 cmH2O was 38.8 ml/kg body weight before acid, and was reduced sharply to 21.1 at 4 h, then increased to 25.6 at 24 h and 32.1 at 48 h. Excess extravascular lung water (EVLW) could account for only part of the volume reductions. Specific compliance ratio of transpulmonary pressure to total lung capacity (CL/TLC) between PL of 5 and 0 cmH2O was reduced from 0.074/cmH2O to 0.050, 0.048, and 0.053/cmH2O, respectively. Saline TLC (PL = 10 cmH2O) changed from 44.8 to 32.4, 34.3, and 45.4 ml/kg, respectively, but CL/TLC did not, suggesting airway obstruction. After injury, trapped volume at PL = 0 increased from 24.9 to 29.2, 43.3, and 37.3% TLC with air, and from 20.3 to 38.5, 33.1, and 28.5%, respectively, with saline. Air volume at a PL = 10 cmH2O on deflation fell from 82.0 to 72.1% TLC at 4 h, but was near control at 24 and 48 h. The reduction in ventilated volume was not reflected in proportionately increased shunt; therefore, some compensatory vasoconstriction must have occurred. We suggest that in affected regions increased surface forces, increased EVLW, and airway obstruction caused reductions of lung volume.

Pulmonary function hyperresponsiveness, defined as enhanced response on reexposure to O3, compared with initial O3 exposure, has been previously noted in consecutive day exposures to high ambient O3 concentrations (i.e., 0.32-0.42 ppm). Effects of consecutive-day exposure to lower O3 concentrations (0.20-0.25 ppm) have yielded equivocal results. To examine the occurrence of hyperresponsiveness at two levels of O3 exposure, 15 aerobically trained males completed seven 1-h exposures of continuous exercise at work rates eliciting a mean minute ventilation of 60 1/min. Three sets of consecutive-day exposures, involving day 1/day 2 exposures to 0.20/0.20 ppm O3, 0.35/0.20 ppm O3, and 0.35/0.35 ppm O3, were randomly delivered via an obligatory mouthpiece inhalation system. A filtered-air exposure was randomly placed 24 h before one of the three sets. Treatment effects were assessed by standard pulmonary function tests, exercise ventilatory pattern (i.e., respiratory frequency, f; and tidal volume, VT) changes and subjective symptom (SS) response. Initial O3 exposures to 0.35 and 0.20 ppm had a statistically significant effect, compared with filtered air, on all measurements. On reexposure to 0.35 ppm O3 24 h after an initial 0.35 ppm O3 exposure, significant hyperresponsiveness was demonstrated for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), f, VT, and total SS score. Exposure to 0.20 ppm O3 24 h after 0.35 ppm O3 exposure, however, resulted in significantly enhanced responses (compared with initial 0.20 ppm O3 exposure) only for FEV1, f, and VT.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction equations developed from previous ozone (O3) exposure studies suggested that athletes exercising at near competitive intensities would be subject to alteration of pulmonary function during exposure to relatively low concentrations of O3. Accordingly we exercised seven trained athletes for 1 h at 75% of maximal O2 consumption in both room air and a 0.21 ppm O3 environment. Pulmonary function tests, including forced expiratory maneuvers and maximum voluntary ventilation (MVV), were performed prior to and immediately following the 1-h test. Significant decreases in forced vital capacity (FVC, -7%), forced expired volume in 1.0 s (-15%), forced expiratory flow over the midhalf of FVC (-18%), and MVV (-17%) were recorded following O3 exposure. The magnitudes of these changes are similar to those observed in subjects performing moderate intermittent exercise for 2 h in a 0.24 ppm O3 environment. Symptoms reported following O3 exposure included laryngeal and/or tracheal irritation and soreness and chest tightness on taking a deep breath. The observed alterations in lung functions in these subjects indicate that individuals performing heavy continuous exercise are more likely to be affected by lower O3 levels.

We exposed 22 healthy adult nonsmoking male subjects for 2 h to filtered air, 1.0 ppm sulfur dioxide (SO2), 0.3 ppm ozone (O3), or the combination of 1.0 ppm SO2 + 0.3 ppm O3. We hypothesized that exposure to near-threshold concentrations of these pollutants would allow us to observe any interaction between the two pollutants that might have been masked by the more obvious response to the higher concentrations of O3 used in previous studies. Each subject alternated 30-min treadmill exercise with 10-min rest periods for the 2 h. The average exercise ventilation measured during the last 5 min of exercise was 38 1/min (BTPS). Forced expiratory maneuvers were performed before exposure and 5 min after each of the three exercise periods. Maximum voluntary ventilation, He dilution functional residual capacity, thoracic gas volume, and airway resistance were measured before and after the exposure. After O3 exposure alone, forced expiratory measurements (FVC, FEV1.0, and FEF25-75%) were significantly decreased. The combined exposure to SO2 + O3 produced similar but smaller decreases in these measures. There were small but significant differences between the O3 and the O3 + SO2 exposure for FVC, FEV1.0, FEV2.0, FEV3.0, and FEF25-75% at the end of the 2-h exposure. We conclude that, with these pollutant concentrations, there is no additive or synergistic effect of the two pollutants on pulmonary function.

We studied the effects of ozone (O3) exposure on airway mucus secretion. Sheep were exposed in vivo to 0.5 ppm O3, 4 h/day for 2 days (acute, n = 6), 6 wks (chronic, n = 6) or 6 wks + 1 wk recovery (chronic + recovery, n = 6). Secretion of glycoproteins (radiolabeled with 35SO4 and [3H]threonine), and transepithelial fluxes of Cl-, Na+ and water were subsequently measured in tracheal tissues in vitro, and were compared with values from control, unexposed sheep (n = 8). Acute O3 exposure increased basal secretion of sulfated glycoproteins (P less than 0.05), but had no effect on ion fluxes. Chronic exposure reduced basal glycoprotein secretion, but increased net Cl- secretion. Under open-circuit conditions, chronic exposure also induced net water secretion (P less than 0.05). With 7 days recovery, basal glycoprotein secretion (predominantly sulfated) was greatly increased above control, while the increased net secretion of Cl- and of water persisted (P less than 0.05). Histology of the airways indicated that acute exposure induced moderate hypertrophy of submucosal glands in the lower trachea (P less than 0.05), while chronic exposure (with and without recovery) induced a large hypertrophy of submucosal glands in both upper and lower trachea (P less than 0.05). Without recovery, however, the gland cells were devoid of secretory material, whereas with recovery they were full of secretory material. This suggests that the decreased glycoprotein secretion with chronic exposure alone resulted from incomplete replenishment of intracellular stores after 6 wks of stimulation. We conclude that both short- and long-term O3 exposure causes airway-mucus hypersecretion.

We measured intrapulmonary deposition of 0. 5-, 1-, 2-, and 3-micron-diameter particles in four subjects on the ground (1 G) and during parabolic flights both in microgravity (microG) and at approximately 1.6 G. Subjects breathed aerosols at a constant flow rate (0.4 l/s) and tidal volume (0.75 liter). At 1 G and approximately 1.6 G, deposition increased with increasing particle size. In microG, differences in deposition as a function of particle size were almost abolished. Deposition was a nearly linear function of the G level for 2- and 3-micron-diameter particles, whereas for 0.5- and 1.0-micron-diameter particles, deposition increased less between microG and 1 G than between 1 G and approximately 1.6 G. Comparison with numerical predictions showed good agreement for 1-, 2-, and 3-micron-diameter particles at 1 and approximately 1.6 G, whereas the model consistently underestimated deposition in microG. The higher deposition observed in microG compared with model predictions might be explained by a larger deposition by diffusion because of a higher alveolar concentration of aerosol in microG and to the nonreversibility of the flow, causing additional mixing of the aerosols.

We used aerosol boluses to study convective gas mixing in the lung of four healthy subjects on the ground (1 G) and during short periods of microgravity (microG) and hypergravity ( approximately 1. 6 G). Boluses of 0.5-, 1-, and 2-micron-diameter particles were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 150 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The dispersion, deposition, and position of the bolus in the expired gas were calculated from these data. For each particle size, both bolus dispersion and deposition increased with Vp and were gravity dependent, with the largest dispersion and deposition occurring for the largest G level. Whereas intrinsic particle motions (diffusion, sedimentation, inertia) did not influence dispersion at shallow depths, we found that sedimentation significantly affected dispersion in the distal part of the lung (Vp >500 ml). For 0.5-micron-diameter particles for which sedimentation velocity is low, the differences between dispersion in microG and 1 G likely reflect the differences in gravitational convective inhomogeneity of ventilation between microG and 1 G.

When modeling intraspecific relationships between selected measurements (Y) for differences in body mass (m) using the allometric equation Y = amb (where a is a constant and b is the exponent parameter), various studies have reported exponents greater than the anticipated 2/3, often closer to the exponent 0.75 identified by Kleiber. A possible explanation for these exponents is proposed based on the findings of Alexander et al. (J. Zool. Lond. 194: 539-552, 1981), who observed that, within a variety of species, larger mammals have a greater proportion of proximal leg muscle mass in relation to their body mass, m1.1. If subjects that are used to record Y exhibit a similar disproportionate increase in muscle mass with body size, then the allometric equation is likely to identify both a contribution proportional to the subject's body mass and a contribution from the disproportionate increase in muscle mass within the group. These confounding influences in Y can be identified separately by incorporating a body size parameter as well as a mass component in the allometric equation. The factor "body size" can be introduced either by partitioning the sample into discrete subgroups according to body size or, in studies involving human subjects, by introducing height as a continuous covariate. In both studies reported involving human maximal exercise, these methods were able to identify a systematic increase in Y with body size, leaving the subject's body mass component, found to be proportional to m2/3, independent of body size.

Intraspecific allometric modeling (Y = a.mass(b), where Y is the physiological dependent variable and a is the proportionality coefficient) of peak oxygen uptake (VO2peak) has frequently revealed a mass exponent (b) greater than that predicted from dimensionality theory, approximating Kleiber's 3/4 exponent for basal metabolic rate. Nevill (J. Appl. Physiol. 77: 2,870-2,873, 1994) proposed an explanation and a method that restores the inflated exponent to the anticipated 2/3. In human subjects, the method involves the addition of "stature" as a continuous predictor variable in a multiple log-linear aggression model: ln Y = a + c. ln stature + b. ln mass + ln epsilon, where c is the general body size exponent and epsilon is the error term. It is likely that serious collinearity confounds may adversely affect the reliability and validity of the model. The aim of this study was to critically examine Nevill's method in modeling VO2peak in prepubertal, teenage, and adult men. A mean exponent of 0.81 (95% confidence interval, 0.65-0.97) was found when scaling by mass alone. Nevill's method reduced the mean mass exponent to 0.67 (95% confidence interval, 0.44-0.9). However, variance inflation factors and tolerance for the log-transformed stature and mass variables exceeded published criteria for severe collinearity. Principal components analysis also diagnosed severe collinearity in two principal components, with condition indexes > 30 and variance decomposition proportions exceeding 50% for two regression coefficients. The derived exponents may thus be numerically inaccurate and unstable. In conclusion, the restoration of the mean mass exponent to the anticipated 2/3 may be a fortuitous statistical artifact.

We assessed the retention and clearance of inhaled particles in six anatomic compartments of the respiratory tract. Hamsters were exposed for 45 min to 0.9-micron fluorescent latex particles either at rest (n = 9) or while running on a laddermill (n = 9). Oxygen consumption, which was used to estimate minute ventilation, was continuously monitored. Three animals from each group, rest and exercise, were killed at 10 min, 24 h, or 7 days after the exposure. Morphometric techniques were used to determine the number of particles retained in nose and oropharynx (NOSE), trachea and extrapulmonary airways, intrapulmonary conducting airways, respiratory bronchioles, alveolar ducts (AD), and alveoli (ALV). At 10 min, total particle retention increased linearly as a function of O2 consumption (slope = 1.4 +/- 0.3 x 10(6) particles.ml-1.g-1.h-1, P less than 0.015). Exercised hamsters retained 4.4 times more total particles in their NOSE than rested hamsters, but parenchymal retention (AD + ALV) was unaffected. After 7 days, 95% of the particles were cleared from the NOSE, 80% from the trachea and extrapulmonary airways, 44% from intrapulmonary conducting airways and respiratory bronchioles, and 16% from AD and ALV. There was evidence of particle redistribution from AD to ALV during the 1st day. We conclude that exercise enhances the deposition of 0.9-micron particles in the upper respiratory tract but not in the parenchyma. Subsequently, the deposited particles are cleared at varying rates depending on the lung compartment.

Thromboxanes (Txs) were implicated as possible participants in the altered microvascular permeability of acute lung injury when the Tx synthase inhibitor, OKY-046, was reported to prevent pulmonary edema induced by phorbol myristate acetate (PMA). Recently, however, we found that OKY-046, at a dose just sufficient to block Tx synthesis in intact dogs, did not prevent PMA-induced pulmonary edema but rather merely reduced it modestly. The present study was designed to explore other mechanisms whereby OKY-046 might prevent PMA-induced pulmonary edema. The finding that 5-lipoxygenase (5-LO) metabolites of arachidonic acid were increased within the lung after PMA administration, coupled with the report that OKY-046 inhibited slow-reacting substance of anaphylaxis formation, permitted formulation of the hypothesis that OKY-046, at a dose in excess of that required to inhibit Tx synthesis, inhibits the formation of a product(s) of 5-LO and, thereby, prevents edema formation. In vehicle-pretreated pentobarbital-anesthetized male mongrel dogs (n = 4), PMA (20 micrograms/kg i.v.) increased pulmonary vascular resistance (PVR) from 4.4 +/- 0.3 to 26.3 +/- 8.8 mmHg.l-1 x min (P < 0.01) and extravascular lung water from 6.7 +/- 0.5 to 19.1 +/- 6.2 ml/kg body wt (P < 0.05). Concomitantly, both TxB2 and leukotriene B4 (LTB4) were significantly increased in the lung. Pretreatment with OKY-046 (100 mg/kg i.v., n = 8) prevented PMA-induced increases in TxB2, LTB4, and pulmonary edema formation but did not prevent the increase in PVR.(ABSTRACT TRUNCATED AT 250 WORDS)

Peptidoleukotrienes may be important mediators of human bronchial asthma. Accordingly, the effects of a selective leukotriene (LT) biosynthesis inhibitor (MK-0591) were assessed in allergic dogs characterized by acute bronchoconstriction and subsequent airway hyperresponsiveness induced by inhaled ragweed allergen. Peak acute increases in airway resistance (Rrs) induced by ragweed were associated with increased bronchoalveolar lavage histamine concentration, and neither parameter was inhibited by MK-0591 (8 micrograms.kg-1.min-1 i.v.). However, the duration of the bronchoconstriction was significantly decreased by MK-0591, with a reduction in the area under the curve of 40% (P < 0.05). Associated with the acute bronchoconstriction in placebo-treated animals was a fivefold increase in urinary LTE4 excretion (as seen with allergic asthmatic patients), which was reduced to < 10% of basal values by MK-0591. Similarly, whole blood LTB4 biosynthesis was abolished in the MK-0591-treated animals. Bronchial hyperresponsiveness preallergen (measured as the percent concentration of acetylecholine required to increase Rrs by 5 cmH2O.l-1.s) tended to improve with MK-0591 (0.41 +/- 0.15 vs. 0.23 +/- 0.05%). Five hours after allergen inhalation, the percent concentration declined substantially in the placebo group (0.07 +/- 0.02%; P < 0.01), revealing an increased airway responsiveness that was significantly blunted by MK-0591 (0.26 +/- 0.07%; P < 0.001). These data suggest that selective inhibition of LT biosynthesis by novel compounds such as MK-0591 may modify the airway changes associated with bronchial hyperresponsiveness, as well as offer symptomatic relief in asthma.

We used the 5-lipoxygenase-activating protein (FLAP) antagonist MK-0591 to investigate the importance of leukotrienes (LT) in causing ozone-induced bronchoconstriction, airway inflammation, and airway hyperresponsiveness in dogs. Six random source dogs were studied. On one day, dogs were treated with MK-0591 (2 mg/kg iv) followed by a continuous intravenous infusion of 8 micrograms.kg-1.min-1. On the other day, the diluent was infused. Acetylcholine airway responsiveness was measured before and 1 h after ozone inhalation (3 ppm for 30 min). On each day, whole blood and bronchoalveolar lavage (BAL) cells were challenged with calcium ionophore to stimulate LTB4 production. Urinary LTE4 levels were measured before and after ozone. MK-0591 inhibited LTB4 production in whole blood by 96% (P = 0.001) and that from BAL cells by 91% (P = 0.001). By contrast, MK-0591 had no effect on ozone-induced bronchoconstriction, airway hyperresponsiveness, or influx of neutrophils into BAL. The mean log difference of the pre- to post-acetylcholine provocative concentration was 0.64 +/- 0.40 during MK-0591 treatment and 0.68 +/- 0.40 during diluent treatment (P = 0.71). These results indicate that peptidoleukotrienes are produced during ozone inhalation and that MK-0591 inhibits LT production in dogs. However, LTs do not play a role in ozone-induced bronchoconstriction, airway inflammation, or airway hyperresponsiveness in dogs.

The purpose of the present experiment was to compare 13CO2 recovery at the mouth, and the corresponding exogenous glucose oxidation computed, during a 100-min exercise at 63 +/- 3% maximal O2 uptake with ingestion of glucose (1.75 g/kg) in six active male subjects, by use of [U-13C] and [1,2-13C]glucose. We hypothesized that 13C recovery and exogenous glucose oxidation could be lower with [1,2-13C] than [U-13C]glucose because both tracers provide [13C]acetate, with possible loss of 13C in the tricarboxylic acid (TCA) cycle, but decarboxylation of pyruvate from [U-13C]glucose also provides 13CO2, which is entirely recovered at the mouth during exercise. The recovery of 13C (25.8 +/- 2.3 and 27.4 +/- 1.2% over the exercise period) and the amounts of exogenous glucose oxidized computed were not significantly different with [1,2-13C] and [U-13C]glucose (28.9 +/- 2.6 and 30.7 +/- 1.3 g, between minutes 40 and 100), suggesting that no significant loss of 13C occurred in the TCA cycle. This stems from the fact that, during exercise, the rate of exogenous glucose oxidation is probably much larger than the flux of the metabolic pathways fueled from TCA cycle intermediates. It is thus unlikely that a significant portion of the 13C entering the TCA cycle could be diverted to these pathways. From a methodological standpoint, this result indicates that when a large amount of [13C]glucose is ingested and oxidized during exercise, 13CO2 production at the mouth accurately reflects the rate of glucose entry in the TCA cycle and that no correction factor is needed to compute the oxidative flux of exogenous glucose.

Skeletal muscle can utilize many different substrates, and traditional methodologies allow only indirect discrimination between oxidative and nonoxidative uptake of substrate, possibly with contamination by metabolism of other internal organs. Our goal was to apply 1H- and 13C-nuclear magnetic resonance spectroscopy to monitor the patterns of [3-13C]lactate and [1,2-13C]acetate (model of simple carbohydrates and fats, respectively) utilization in resting vs. contracting muscle extracts of the isolated perfused rat hindquarter. Total metabolite concentrations were measured by using NADH-linked fluorometric assays. Fractional oxidation of [3-13C]lactate was unchanged by contraction despite vascular endogenous lactate accumulation. Although label accumulated in several citric acid cycle (CAC) intermediates, contraction did not increase the concentration of CAC intermediates in any muscle extracts. We conclude that 1) the isolated rat hindquarter is a viable, well-controlled model for measuring skeletal muscle 13C-labeled substrate utilization; 2) lactate is readily oxidized even during contractile activity; 3) entry and exit from the CAC, via oxidative and nonoxidative pathways, is a component of normal muscle metabolism and function; and 4) there are possible differences between gastrocnemius and soleus muscles in utilization of nonoxidative pathways.

Hens acclimated to an altitude of 3,800 m (PB 480 Torr) were transferred to 1,200 m (PB 657 Torr). Eggs were collected before departure and daily after the transfer so that changes in eggshell conductance could be studied. Over the next 2 mo eggshell conductance increased 30%, presumably to compensate for the 37% reduction (from 657 to 480 Torr) in gas diffusivity at the lower altitude. Measurements of shell thickness and number of pores in the shell allow one to calculate that most of the change in total pore area occurred by an increase in cross-sectional area of individual pores.

This study examined the hypothesis that running speed over 800- and 1,500-m races is regulated by the prevailing anaerobic (oxygen independent) store (ANS) at each instant of the race up until the all-out phase of the race over the last several meters. Therefore, we hypothesized that the anaerobic power that allows running above the speed at maximal oxygen uptake (VO2max) is regulated by ANS, and as a consequence the time limit at the anaerobic power (tlim PAN=ANS/PAN) is constant until the final sprint. Eight 800-m and seven 1,500-m male runners performed an incremental test to measure VO2max and the minimal velocity associated with the attainment of VO2max (vVO2max), referred to as maximal aerobic power, and ran the 800-m or 1,500-m race with the intent of achieving the lowest time possible. Anaerobic power (PAN) was measured as the difference between total power and aerobic power, and instantaneous ANS as the difference between end-race and instantaneous accumulated oxygen deficits. In 800 m and 1,500 m, tlim PAN was constant during the first 70% of race time in both races. Furthermore, the 1,500-m performance was significantly correlated with tlim PAN during this period (r=-0.92, P<0.01), but the 800-m performance was not (r=-0.05, P=0.89), although it was correlated with the end-race oxygen deficit (r=-0.70, P=0.05). In conclusion, this study shows that in middle-distance races over both 800 m and 1,500 m, the speed variations during the first 70% of the race time serve to maintain constant the time to exhaustion at the instantaneous anaerobic power. This observation is consistent with the hypothesis that at any instant running speed is controlled by the ANS remaining.

Eleven nonsmoking male resting subjects were exposed to two transient CO profiles to examine whether the resultant carboxyhemoglobin (HbCO) differs with CO concentration for a fixed total CO dose and to determine the predictive capability of the theoretical model of Coburn et al. (J. Clin. Invest. 44: 1899-1910, 1965) using measured alveolar ventilation. One profile consisted of five sequential exposures to 1,500 ppm CO for 5 min each and spaced 3 min apart. The other consisted of five sequential exposures to 7,500 ppm CO for 1 min each and spaced 7 min apart. The subjects, therefore, were exposed to the same overall nominal dose of 37,500 ppm.min. During the experiment, the subject's ventilatory functions and respiratory gases were recorded continuously, and the resultant HbCO% was measured in venous blood samples by gas chromatography. Mean increase (+/- SD) in HbCO% per exposure was 2.08 +/- 0.27% for the 1,500 ppm CO exposures and 2.05 +/- 0.29% for the 7,500 ppm CO exposures with no significant difference between the two. When the measured values of the subject's alveolar ventilation were applied to the theoretical model of Coburn et al., the predicted rate of HbCO% formation was found to agree with the experimental results.

Paraquat (PQ; 1,1'-dimethyl-4,4'-bipyridylium dichloride), a widely used herbicide, causes pulmonary edema by a cyclic oxidation and reduction reaction with oxygen molecules with the production of oxygen free radicals. Because fructose 1,6-diphosphate (FDP) has recently been shown to inhibit the generation of oxygen free radicals by activated neutrophils, we determined the effects of FDP on PQ-induced increase in microvascular permeability in isolated blood-perfused dog lungs. Vascular permeability was assessed using the capillary filtration coefficient (Kf,c) and isogravimetric capillary pressure (Pc,i). There was no change in these variables over 5 h in the control lungs treated with saline (n = 5). A significant increase in Kf,c and a decrease in Pc,i, both of which indicated increased vascular permeability, were observed at 5 h of perfusion with 4 x 10(-3) M PQ (n = 5). Unexpectedly, an increase in microvascular permeability occurred within 4 h after administration of PQ in the lungs that were pretreated with FDP (2.7-14.2 mM, n = 6). Moreover the increases of Kf,c in the FDP-pretreated lungs were significantly greater than those in the lungs treated with PQ alone. Also, the final-to-initial lung weight ratio of the FDP-pretreated group was greater than those of the other groups. Thus the FDP dose used in the present study accentuated rather than prevented the PQ lung injury.

Glucose 1,6-bisphosphate (G-1,6-P2) is a potent activator of phosphofructokinase (PFK) and an inhibitor of hexokinase in vitro. It has been suggested that increases in G-1,6-P2 are a main means by which PFK can achieve significant catalytic function in vivo despite falling pH and that increases in G-1,6-P2 will inhibit hexokinase in vivo. The purpose of the present study was to determine whether contraction-induced changes in flux through PFK and hexokinase are associated with changes in G-1,6-P2 in skeletal muscle. Ten men performed bicycle exercise for 10 min at 40 and 75% of maximal O2 uptake (VO2max) and to fatigue [4.8 +/- 0.6 (SE) min] at 100% VO2max. Biopsies were obtained from the quadriceps femoris muscle at rest and after each work load and analyzed for G-1,6-P2. G-1,6-P2 averaged 111 +/- 13 mumol/kg dry wt at rest and 121 +/- 16, 123 +/- 15, and 123 +/- 11 mumol/kg dry wt after the low-, moderate-, and high-intensity exercise bouts, respectively (P less than 0.05 for all means vs. rest). Flux through PFK was estimated to increase exponentially as the exercise intensity increased and muscle pH decreased at the higher work loads, whereas flux through hexokinase was estimated to increase during exercise at 40 and 75% VO2max but decrease sharply at 100% VO2max. These data demonstrate that flux through neither PFK nor hexokinase is mediated by changes in G-1,6-P2 in human skeletal muscle during short-term dynamic exercise.