Carbonyl sulfide (COS) as a tracer for canopy photosynthesis, transpiration and stomatal conductance: potential and limitations

The theoretical basis for the link between the leaf exchange of carbonyl sulfide (COS), carbon dioxide (CO(2)) and water vapour (H(2)O) and the assumptions that need to be made in order to use COS as a tracer for canopy net photosynthesis, transpiration and stomatal conductance, are reviewed. The ratios of COS to CO(2) and H(2)O deposition velocities used to this end are shown to vary with the ratio of the internal to ambient CO(2) and H(2)O mole fractions and the relative limitations by boundary layer, stomatal and internal conductance for COS. It is suggested that these deposition velocity ratios exhibit considerable variability, a finding that challenges current parameterizations, which treat these as vegetation-specific constants. COS is shown to represent a better tracer for CO(2) than H(2)O. Using COS as a tracer for stomatal conductance is hampered by our present poor understanding of the leaf internal conductance to COS. Estimating canopy level CO(2) and H(2)O fluxes requires disentangling leaf COS exchange from other ecosystem sources/sinks of COS. We conclude that future priorities for COS research should be to improve the quantitative understanding of the variability in the ratios of COS to CO(2) and H(2)O deposition velocities and the controlling factors, and to develop operational methods for disentangling ecosystem COS exchange into contributions by leaves and other sources/sinks. To this end, integrated studies, which concurrently quantify the ecosystem-scale CO(2), H(2)O and COS exchange and the corresponding component fluxes, are urgently needed.     

Inhaled carbon monoxide and hyperoxic lung injury in rats

Because carbon monoxide (CO) has been proposed to have anti-inflammatory properties, we sought protective effects of CO in pulmonary O(2) toxicity, which leads rapidly to lung inflammation and respiratory failure. Based on published studies, we hypothesized that CO protects the lung against O(2) by selectively increasing expression of antioxidant enzymes, thereby decreasing oxidative injury and inflammation. Rats exposed to O(2) with or without CO [50-500 parts/million (ppm)] for 60 h were compared for lung wet-to-dry weight ratio (W/D), pleural fluid volume, myeloperoxidase (MPO) activity, histology, expression of heme oxygenase-1 (HO-1), and manganese superoxide dismutase (Mn SOD) proteins. The brains were evaluated for histological evidence of damage from CO. In O(2)-exposed animals, lung W/D increased from 4.8 in normal rats to 6.3; however, only CO at 200 and 500 ppm decreased W/D significantly (to 5.9) during O(2) exposure. Large volumes of pleural fluid accumulated in all rats, with no significant CO treatment effect. Lung MPO values increased after O(2) and were not attenuated by CO treatment. CO did not enhance lung expression of oxidant-responsive proteins Mn SOD and HO-1. Animals receiving O(2) and CO at 200 or 500 ppm showed significant apoptotic cell death in the cortex and hippocampus by immunochemical staining. Thus significant protection by CO against O(2)-induced lung injury could not be confirmed in rats, even at CO concentrations associated with apoptosis in the brain.     

Application of carbon monoxide diffusing capacity in the mouse lung

In the past decade the mouse has become the primary animal model of a variety of lung diseases. To assess various mechanisms underlying such pathologies, it is essential to make functional measurements that can reflect the developing pathology. In this regard, the diffusing capacity for carbon monoxide is a variable that directly reflects structural changes in the lung. Although measurement of single-breath diffusing capacity of the lung for carbon monoxide (DL(CO)) has also been previously reported in mice by a number of investigators, a number of technical issues have precluded routine and widespread use of this metric in mouse models. In the present report, we describe a means to quickly and simply measure a dimensionless variable closely related to the DL(CO) in mice, termed a diffusion factor for carbon monoxide (DF(CO)). The DF(CO) procedure involves a 9-s lung inflation with tracer gases in an anesthetized mouse, followed by a 1-min gas analysis time. We have tested the approach with two common models of lung pathology, elastase-induced emphysema and bleomycin-induced fibrosis. Results show a significant 15% reduction in DF(CO) in emphysema, and a 41% reduction in the fibrosis model. Repeat measurements within a mouse were found to be highly reproducible. This pulmonary function test can thus be used to detect structural changes with these pathological models. The method can also be used to measure changes in pulmonary blood volume, since the uptake of CO is highly dependent on this variable in addition to the gas exchange surface area.     

Effect of transrespiratory pressure on PETCO2-PaCO2 and ventilatory reflexes in humans

Inspiratory muscle activity increases when lung volume is increased by continuous positive-pressure breathing in conscious human subjects (Green et al., Respir. Physiol. 35: 283-300, 1978). Because end-tidal CO2 pressure (PETCO2) does not change, these increases have not been attributed to chemoreflexes. However, continuous positive-pressure breathing at 20 cmH2O influences the end-tidal to arterial CO2 pressure differences (Folkow and Pappenheimer, J. Appl. Physiol. 8: 102-110, 1955). We have compared PETCO2 with arterial CO2 pressure (PaCO2). We have compared PETCO2 with arterial CO2 pressure (PaCO2) in healthy human subjects exposed to continuous positive airway pressure (10 cmH2O) or continuous negative pressure around the torso (-15 cmH2O) sufficient to increase mean lung volume by about 650 ml. The difference between PETCO2 and PaCO2 was not decreased, and we conclude that PETCO2 is a valid measure of chemical drive to ventilation in such circumstances. We observed substantial increases in respiratory muscle electromyograms during pressure breathing as seen previously and conclude this response must originate by proprioception. On average, the compensation of tidal volume thus afforded was complete, but the wide variability of individual responses suggests that there was a large cerebral cortical component in the responses seen here.     

Diaphragmatic function during hypercapnia: neonatal and developmental aspects

The effect of acute hypercapnia on diaphragmatic force output was studied in 6 young (4-8 days) and 6 older (16-20 days) anesthetized, spontaneously breathing piglets. Diaphragmatic force output was assessed by analysis of the transdiaphragmatic pressure (Pdi) generated during phrenic nerve stimulation. Pdi was measured under base-line conditions (50% O2-50% N2) and after 10 min of hypercapnia induced by breathing 5, 10, or 15% CO2 balanced with N2 and 50% O2. Pdi was significantly less than base line during the 10 and 15% hypercapnic conditions in the young (P less than 0.05) but not the older piglets. End-expiratory lung volume was noted to decrease during 15% CO2 hypercapnia. Force output augmentation occurred at this lower end-expiratory lung volume and was significantly greater in the older piglet compared with its younger counterpart (P less than 0.05). When the effects of lung volume on Pdi were corrected for, there was no age-related difference in the response to 15% CO2 hypercapnia. We conclude that severe hypercapnia has a depressant effect on diaphragmatic force output in both young and older piglets, and a differential augmentation in diaphragmatic force-output gain occurs at lower end-expiratory lung volume between young and older piglets, with the greater output occurring in the more mature animal.     

Measurement of lung water in dog lobes using inhaled C15O2 and injected H215O

Indicator-dilution analysis was used in a recirculation-free isolated dog lobe preparation to compare an inhaled water tracer (C15O2) and an injected water tracer (H215O) with direct weighing as a measure of total lung water. Residue detection (counting over the lung) was compared with outflow detection (counting over the venous effluent). With outflow detection, inhaled C15O2 measured 74% and injected H215O 90% of the gravimetric lung water. In hemodynamic edema, the increase in lung water measured by residue detection of both tracers correlated well with increases in weight (r = 0.92, slope = 1.03). However, outflow detection of both tracers underestimated the lung water increase by 53% in edema (r = 0.88, slope = 0.47). Thus, in edema, equilibration of both tracers within the lung water volume is rapid, but clearance from the lung is delayed because slowly clearing water pools develop. The errors caused by inhomogeneity of perfusion distribution were investigated after pulmonary arterial injection of 34-, 50-, and 175-micrometers spheres. For the same lung weight, C15O2 transit was delayed and H215O transit accelerated greatly by the 175-micrometers spheres and slightly by the 50-micrometers spheres.     

Hypercapnia does not affect functional residual capacity enlargement induced by chronic hypoxia

To determine whether changes in partial pressure of CO2 participate in mechanism enlarging the lung functional residual capacity (FRC) during chronic hypoxia, we measured FRC and ventilation in rats exposed either to poikilocapnic (group H, F(I)O2 0.1, F(I)CO2 <0.01) or hypercapnic (group H+CO2, F(I)O2 0.1, F(I)CO2 0.04-0.05) hypoxia for the three weeks and in the controls (group C) breathing air. At the end of exposure a body plethysmograph was used to measure ventilatory parameters (V'(E), f(R), V(T)) and FRC during air breathing and acute hypoxia (10 % O2 in N2). The exposure to hypoxia for three weeks increased FRC measured during air breathing in both experimental groups (H: 3.0+/-0.1 ml, H+CO2: 3.1+/-0.2 ml, C: 1.8+/-0.2 ml). During the following acute hypoxia, we observed a significant increase of FRC in the controls (3.2+/-0.2 ml) and in both experimental groups (H: 3.5+/-0.2 ml, H+CO2: 3.6+/-0.2 ml). Because chronic hypoxia combined with chronic hypercapnia and chronic poikilocapnic hypoxia induced the same increase of FRC, we conclude that hypercapnia did not participate in the FRC enlargement during chronic hypoxia.     

Cardiopulmonary adaptations to pneumonectomy in dogs. I. Maximal exercise performance.

Maximal exercise performance was evaluated in four adult foxhounds after right pneumonectomy (removal of 58% of lung) and compared with that in seven sham-operated control dogs 6 mo after surgery. Maximal O2 uptake (ml O2.min-1.kg-1) was 142.9 +/- 1.9 in the sham group and 123.0 +/- 3.8 in the pneumonectomy group, a reduction of 14% (P less than 0.001). Maximal stroke volume (ml/kg) was 2.59 +/- 0.10 in the sham group and 1.99 +/- 0.05 in the pneumonectomy group, a reduction of 23% (P less than 0.005). Lung diffusing capacity (DL(CO)) (ml.min-1.Torr-1.kg-1) reached 2.27 +/- 0.08 in the combined lungs of the sham group and 1.67 +/- 0.07 in the remaining lung of the pneumonectomy group (P less than 0.001). In the pneumonectomy group, DL(CO) of the left lung was 76% greater than that in the left lung of controls. Blood lactate concentration and hematocrit were significantly higher at exercise in the pneumonectomy group. We conclude that, in dogs after resection of 58% of lung, O2 uptake, cardiac output, stroke volume, and DL(CO) at maximal exercise were restricted. However, the magnitude of overall impairment was surprisingly small, indicating a remarkable ability to compensate for the loss of one lung. This compensation was achieved through the recruitment of reserves in DL(CO) in the remaining lung, the development of exercise-induced polycythemia, and the maintenance of a relatively large stroke volume in the face of an increased pulmonary vascular resistance.     

Effect of ventilation on pulmonary blood volume of the fetal lamb.

Blood volume changes in the fetal lung following the onset of ventilation were studied by isotopic measurement of red blood cell and plasma volume in rapidly frozen lungs of ten near term fetal lambs. Total pulmonary blood volumes of fetal lambs ventilated with 3% O2 and 7% CO2 in nitrogen (so that blood gas levels were little changed from fetal values), or with air, were compared with measurements in unventilated lambs. Regional correlations of blood volume and blood flow (measured with isotope-labeled microemboli) within the lungs were also examined. Total pulmonary blood volume averaged 5.6 ml/kg body weight in unventilated fetal lambs and was approximately 43% greated in fetal lambs after 5-20 min of air ventilation, but not significantly different in lambs ventilated with 3% O2 and 7% CO2 in nitrogen. Thus it is ventilation with air, rather than the introduction of gas into the alveoli, which enlarges the fetal pulmonary vascular bed. Regional pulmonary blood volume and blood flow were correlated, though poorly, in air-ventilated lungs, but not in lungs ventilated with 3% O2 and 7% CO2 in nitrogen; this suggests that a common factor may operate to increase both blood flow and blood volume in the fetal lung following the introduction of air.     

(N-succinimidyl 4-pentynoate)hexacarbonyldicobalt: a transition-metal carbonyl complex having similar uses to the Bolton-Hunter reagent

The synthesis of the transition-metal carbonyl complex (N-succinimidyl 4-pentynoate)hexacarbonyldicobalt [[(C4H4O2N)O(CO)CH2CH2C identical to CH]Co2(CO)6] is described. This cobalt carbonyl complex is structurally similar to the Bolton-Hunter conjugation reagent and has been successfully employed as a nonradioactive tracer for labeling the drug carbamazepine. The metal carbonyl tracer can be detected at extremely low concentrations (ca. 1 pmol) by FT-IR spectroscopy in the v(CO) region (2150-1800 cm-1). The cobalt carbonyl labeled carbamazepine retains good recognition for anti-carbamazepine antibodies. This novel labeling procedure, which can be broadly termed carbonylmetalloimmunoassay (CMIA), has considerable potential for assaying a wide range of biological materials.     

Splenectomy impairs diffusive oxygen transport in the lung of dogs.

The spleen acts as an erythrocyte reservoir in highly aerobic species such as the dog and horse. Sympathetic-mediated splenic contraction during exercise reversibly enhances convective O2 transport by increasing hematocrit, blood volume, and O2-carrying capacity. Based on theoretical interactions between erythrocytes and capillary membrane (Hsia CCW, Johnson RL Jr, and Shah D. J Appl Physiol 86: 1460-1467, 1999) and experimental findings in horses of a postsplenectomy reduction in peripheral O2-diffusing capacity (Wagner PD, Erickson BK, Kubo K, Hiraga A, Kai M, Yamaya Y, Richardson R, and Seaman J. Equine Vet J 18, Suppl: 82-89, 1995), we hypothesized that splenic contraction also augments diffusive O2 transport in the lung. Therefore, we have measured lung diffusing capacity (DL(CO)) and its components during exercise by a rebreathing technique in six adult foxhounds before and after splenectomy. Splenectomy eliminated exercise-induced polycythemia, associated with a 30% reduction in maximal O2 uptake. At any given pulmonary blood flow, DL(CO) was significantly lower after splenectomy owing to a lower membrane diffusing capacity, whereas pulmonary capillary blood volume changed variably; microvascular recruitment, indicated by the slope of the increase in DL(CO) with respect to pulmonary blood flow, was also reduced. We conclude that splenic contraction enhances both convective and diffusive O2 transport and provides another compensatory mechanism for maintaining alveolar O2 transport in the presence of restrictive lung disease or ambient hypoxia.     

Mechanisms of gas exchange response to lung volume reduction surgery in severe emphysema

Lung volume reduction surgery (LVRS) improves lung function, respiratory symptoms, and exercise tolerance in selected patients with chronic obstructive pulmonary disease, who have heterogeneous emphysema. However, the reported effects of LVRS on gas exchange are variable, even when lung function is improved. To clarify how LVRS affects gas exchange in chronic obstructive pulmonary disease, 23 patients were studied before LVRS, 14 of whom were again studied afterwards. We performed measurements of lung mechanics, pulmonary hemodynamics, and ventilation-perfusion (Va/Q) inequality using the multiple inert-gas elimination technique. LVRS improved arterial Po? (Pa(O?)) by a mean of 6 Torr (P = 0.04), with no significant effect on arterial Pco? (Pa(CO?)), but with great variability in both. Lung mechanical properties improved considerably more than did gas exchange. Post-LVRS Pa(O?) depended mostly on its pre-LVRS value, whereas improvement in Pa(O(2)) was explained mostly by improved Va/Q inequality, with lesser contributions from both increased ventilation and higher mixed venous Po(2). However, no index of lung mechanical properties correlated with Pa(O?). Conversely, post-LVRS Pa(CO?) bore no relationship to its pre-LVRS value, whereas changes in Pa(CO?) were tightly related (r2 = 0.96) to variables, reflecting decrease in static lung hyperinflation (intrinsic positive end-expiratory pressure and residual volume/total lung capacity) and increase in airflow potential (tidal volume and maximal inspiratory pressure), but not to Va/Q distribution changes. Individual gas exchange responses to LVRS vary greatly, but can be explained by changes in combinations of determining variables that are different for oxygen and carbon dioxide.     

Respiratory adaptation to chronic hypercapnia in newborn rats

We asked 1) whether newborn rats respond to chronic hypercapnia with a persistent increase in ventilation and 2) whether changes in lung mass were accompanying the respiratory adaptation to chronic hypercapnia, as previously observed during neonatal chronic hypoxia. Five litters of rats were kept in 7% CO2 (with 21% O2) from day 1 to 7 after birth (CO2exp) and compared with six litters of control rats growing in normocapnia-normoxia (C). Body weight was similar between the two groups. Ventilation, measured by flow plethysmography, increased in CO2exp from day 2 and remained steadily elevated, and at day 7 it almost doubled (174%) the C value because of the large increase in tidal volume and mean inspiratory flow (192 and 189%, respectively) with no changes in respiratory frequency. Two days after return to normocapnia, ventilation was still 33% higher than in C; at this time, acute exposure to hypercapnia increased ventilation relatively less in the CO2exp than in C because of a lower increase in tidal volume. Neither the lung weight-to-body weight nor the heart weight-to-body weight ratios increased in CO2exp. We conclude that 1) chronic hypercapnia in newborn rats induces a steady increase in ventilation, which persists at least 2 days after return to normocapnia with a reduction in the acute response to CO2, and 2) hyperventilation per se is not the cause of the increased lung mass observed during chronic neonatal hypoxia.     

Pulmonary circulation in different gaseous media

The ultrasonic method was used in acute experiments on cats with an open (under artificial lung ventilation) and closed chest to explore lung circulation in a changed gaseous medium. Moderate hypoxia (10% O2) and hypercapnia (5, 10% CO2) induce a 10-15% decrease in the lung blood flow in the inferolobular pulmonary artery in the presence of unchanged or slightly elevated minute volume of the heart. The higher hypoxia (5% O2) provokes inconclusive changes in the lung blood flow: biphasic response or increase. It is assumed that considerable elevation of blood pressure in the common pulmonary artery in all the cases points to vasoconstriction that occurs under the effect of hypoxia and hypercapnia.     

Ventilatory responses to increased blood flow and decreased lung volume in awake dogs

The effect of decreased lung volume on ventilatory responses to arteriovenous fistula-induced increased cardiac output was studied in four chronic awake dogs. Lung volume decreases were imposed by application of continuous negative-pressure breathing of -10 cmH2O to the trachea. The animals were surgically prepared with chronic tracheostomy, indwelling carotid artery catheter, and bilateral arteriovenous femoral shunts. Control arteriovenous blood flow was 0.5 l/min, and test flow level was 2.0 l/min. Arterial blood CO2 tension (PaCO2) was continuously monitored using an indwelling Teflon membrane mass spectrometer catheter, and inhaled CO2 was given to maintain isocapnia throughout. Increased fistula flow alone led to a mean 52% increase in cardiac output (CO), whereas mean systemic arterial blood pressure (Psa) fell 4% (P less than 0.01). Negative-pressure breathing alone raised Psa by 3% (P less than 0.005) without a significant change in CO. Expired minute ventilation (VE) increased by 27% (P less than 0.005) from control in both of these conditions separately. Combined increased flow and negative pressure led to a 50% increase in CO and 56% increase in VE (P less than 0.0025) without any significant change in Psa. Effects of decreased lung volume and increased CO appeared to be additive with respect to ventilation and to occur under conditions of constant PaCO2 and Psa. Because both decreased lung volume and increased CO occur during normal exercise, these results suggest that mechanisms other than chemical regulation may play an important role in the control of breathing and contribute new insights into the isocapnic exercise hyperpnea phenomenon.     

Effects of hypoxia on pulmonary microvascular volume

To determine the effects of alveolar hypoxia on pulmonary microvascular volume, X-ray microfocal angiographic images of isolated perfused dog lung lobes were obtained during passage of a bolus of radiopaque contrast medium during both normoxic (alveolar gas, 15% O(2), 6% CO(2), and 79% N(2)) and hypoxic (3% O(2), 6% CO(2), and 91% N(2)) conditions. Regions of interest (ROIs) over the lobar artery and vein at low magnification and a feeding artery ( approximately 500 microm diameter) and the nearby microvasculature (vessels smaller than approximately 50 microm) at high magnification were identified, and X-ray absorbance vs. time curves were acquired under both conditions from the same ROIs. The total pulmonary vascular volume was calculated from the flow and the mean transit time for the contrast medium passage from the lobar artery to lobar vein. The fractional changes in microvascular volume were determined from the areas under the high-magnification X-ray absorbance curves. Hypoxia decreased lobar volume by 13 +/- 3% (SE) and regional microvascular volume by 26 +/- 4% (SE). Given the morphometry of the lung vasculature, these results suggest that capillary volume was decreased by hypoxia.     

Functional residual capacity and ventilation homogeneity in mechanically ventilated small neonates.

A modification of a computerized tracer gas (SF6) washout method was designed for serial measurements of functional residual capacity (FRC) and ventilation homogeneity in mechanically ventilated very-low-birth-weight infants with tidal volumes down to 4 ml. The method, which can be used regardless of the inspired O2 concentration, gave accurate and reproducible results in a lung model and good agreement compared with He dilution in rabbits. FRC was measured during 2-4 cmH2O of positive end-expiratory pressure (PEEP) in 15 neonates (700-1,950 g), most of them with mild-to-moderate respiratory distress syndrome. FRC increased with body weight and decreased (P less than 0.05) with increasing O2 requirement. Change to zero end-expiratory pressure caused an immediate decrease in FRC by 29% (P less than 0.01) and gave FRC (ml) = -1.4 + 17 x weight (kg) (r = 0.83). Five minutes after PEEP was discontinued (n = 12), FRC had decreased by a further 16% (P less than 0.01). The washout curves indicated a near-normal ventilation homogeneity not related to changes in PEEP. This was interpreted as evidence against the presence of large volumes of trapped alveolar gas.     

System of automated gas-exchange analysis for the investigation of metabolic processes.

Conventional gas-exchange instruments are confined to the measurement of O(2) consumption (VO(2)) and CO(2) production (VCO(2)) and are subject to a variety of errors. This handicaps the performance of these devices at inspired O(2) fraction (FI(O(2))) > 0.40 and limits their applicability to indirect calorimetry only. We describe a device based on the automation of the Douglas bag technique that is capable of making continuous gas-exchange measurements of multiple species over a broad range of experimental conditions. This system is validated by using a quantitative methanol-burning lung model modified to provide reproducible (13)CO(2) production. The average error for VO(2) and VCO(2) over the FI(O(2)) range of 0.21-0.8. is 2.4 and 0.8%, respectively. The instrument is capable of determining the differential atom% volume of known references of (13)CO(2) to within 3.4%. This device reduces the sources of error that thwart other instruments at FI(O(2)) > 0. 40 and demonstrates the capacity to explore other expressions of metabolic activity in exhaled gases related to the excretion of (13)CO(2).     

Assessing recruitment of lung diffusing capacity in exercising guinea pigs with a rebreathing technique.

Noninvasive techniques for assessing cardiopulmonary function in small animals are limited. We previously developed a rebreathing technique for measuring lung volume, pulmonary blood flow, diffusing capacity for carbon monoxide (Dl(CO)) and its components, membrane diffusing capacity (Dm(CO)) and pulmonary capillary blood volume (Vc), and septal volume, in conscious nonsedated guinea pigs at rest. Now we have extended this technique to study guinea pigs during voluntary treadmill exercise with a sealed respiratory mask attached to a body vest and a test gas mixture containing 0.5% SF(6) or Ne, 0.3% CO, and 0.8% C(2)H(2) in 40% or 98% O(2). From rest to exercise, O(2) uptake increased from 12.7 to 25.5 ml x min(-1) x kg(-1) while pulmonary blood flow increased from 123 to 239 ml/kg. The measured Dl(CO), Dm(CO), and Vc increased linearly with respect to pulmonary blood flow as expected from alveolar microvascular recruitment; body mass-specific relationships were consistent with those in healthy human subjects and dogs studied with a similar technique. The results show that 1) cardiopulmonary interactions from rest to exercise can be measured noninvasively in guinea pigs, 2) guinea pigs exhibit patterns of exercise response and alveolar microvascular recruitment similar to those of larger species, and 3) the rebreathing technique is widely applicable to human ( approximately 70 kg), dog (20-30 kg), and guinea pig (1-1.5 kg). In theory, this technique can be extended to even smaller animals provided that species-specific technical hurdles can be overcome.     

Influence of expiratory loading and hyperinflation on cardiac output during exercise.

Patients with obstructive lung disease are exposed to expiratory loads (ELs) and dynamic hyperinflation as a consequence of expiratory flow limitation. To understand how these alterations in lung mechanics might affect cardiac function, we examined the influence of a 10-cm H2O EL, alone and in combination with voluntary hyperinflation (ELH), on pulmonary pressures [esophageal (Pes) and gastric (Pg)] and cardiac output (CO) in seven healthy subjects. CO was determined by using an acetylene method at rest and at 40 and 70% of peak work. At rest and during exercise, EL resulted in an increase in Pes and Pg (7-18 cm H2O; P < 0.05) and a decrease in CO (from 5.3 +/- 1.8 to 4.5 +/- 1.4, 12.2 +/- 2.2 to 11.2 +/- 2.2, and 16.3 +/- 3.3 to 15.2 +/- 3.2 l/min for rest, 40% peak work, and 70% peak work, respectively; P < 0.05), which remained depressed after an additional 2 min of EL. With ELH, CO increased at rest and both exercise loads (relative to EL only) but remained below control values. The changes in CO were due to a reduction in stroke volume with a tendency for stroke volume to fall further with prolonged EL. There was a negative correlation between CO and the increase in expiratory Pes and Pg with EL (R = -0.58 and -0.60; P < 0.01), whereas the rise in CO with subsequent hyperinflation was related to a more negative Pes (R = 0.72; P < 0.01). In conclusion, EL leads to a reduction in CO, which appears to be primarily related to increases in expiratory abdominal and intrathoracic pressure, whereas ELH resulted in an improved CO, suggesting that lung inflation has little impact on cardiac function.