Steady-state measurement of NO and CO lung diffusing capacity on moderate exercise in men.

Using a rapidly responding nitric oxide (NO) analyzer, we measured the steady-state NO diffusing capacity (DL(NO)) from end-tidal NO. The diffusing capacity of the alveolar capillary membrane and pulmonary capillary blood volume were calculated from the steady-state diffusing capacity for CO (measured simultaneously) and the specific transfer conductance of blood per milliliter for NO and for CO. Nine men were studied bicycling at an average O(2) consumption of 1.3 +/- 0.2 l/min (mean +/- SD). DL(NO) was 202.7 +/- 71.2 ml. min(-1). Torr(-1) and steady-state diffusing capacity for CO, calculated from end-tidal (assumed alveolar) CO(2), mixed expired CO(2), and mixed expired CO, was 46.9 +/- 12.8 ml. min(-1). Torr(-1). NO dead space = (VT x FE(NO) - VT x FA(NO))/(FI(NO) - FA(NO)) = 209 +/- 88 ml, where VT is tidal volume and FE(NO), FI(NO), and FA(NO) are mixed exhaled, inhaled, and alveolar NO concentrations, respectively. We used the Bohr equation to estimate CO(2) dead space from mixed exhaled and end-tidal (assumed alveolar) CO(2) = 430 +/- 136 ml. Predicted anatomic dead space = 199 +/- 22 ml. Membrane diffusing capacity was 333 and 166 ml. min(-1). Torr(-1) for NO and CO, respectively, and pulmonary capillary blood volume was 140 ml. Inhalation of repeated breaths of NO over 80 s did not alter DL(NO) at the concentrations used.     

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 lung volume and positional changes on pulmonary diffusing capacity and its components.

Normal subjects have a larger diffusing capacity normalized per liter alveolar volume (DL/VA) in the supine than in the sitting position. Body position changes total lung diffusing capacity (DL), DL/VA, membrane conductance (Dm), and effective pulmonary capillary blood volume (Qc) as a function of alveolar volume (VA). These functions were studied in 37 healthy volunteers. DL/VA vs. VA yields a linear relationship in sitting as well as in supine position. Both have a negative slope but usually do not run parallel. In normal subjects up to 50 yr old DL/VA and DL increased significantly when subjects moved from a sitting to a supine posture at volumes between 50 and 100% of total lung capacity (TLC). In subjects greater than 50 yr old the responses of DL/VA and DL to change in body position were not significant at TLC. Functional residual capacity (FRC) decreases and DL/VA increases in all normal subjects when they change position from sitting to supine. When DL/VA increases more than predicted from the DL/VA vs. VA relationship in a sitting position, we may infer an increase in effective Qc in the supine position. In 56% of the volunteers, supine DL was smaller than sitting DL despite a higher DL/VA at FRC in the supine position because of the relatively larger decrease in FRC. When the positional response at TLC is studied, an estimation obtained accidentally at a volume lower than TLC may influence results. Above 80% of TLC, Dm decreased significantly from sitting to supine. Below this lung volume the decrease was not significant. The relationship between Qc and VA was best described by a second-order polynomial characterized by a maximum Qc at a VA greater than 60% of TLC. Qc was significantly higher in the supine position than in the sitting position, but the difference became smaller with increasing age. In observing the sitting and supine positions, we saw a decrease in maximum Qc normalized per square meter of body surface area with age.     

Regional lung density and blood volume in nonsmoking and smoking subjects measured by PET

Regional lung density (DL) and regional fractional pulmonary blood volume (VB) were measured quantitatively during tidal breathing in 30 healthy supine subjects (15 smokers and 15 nonsmokers) in a 1.7-cm-thick midthoracic cross section using positron emission tomography (PET) and 11CO (inhaled)-labeled erythrocytes. Regional alveolar volume (VA), extravascular lung density (DEV), and relative alveolar size (Valv = VA/DEV) were calculated. For the nonsmokers, mean values (+/- SD between subjects) for the right lung were as follows: DL, 0.28 +/- 0.03 g/cm3; DEV, 0.10 +/- 0.02 g/cm3; and Valv, 7.1 +/- 1.9 ml/g lung tissue. In the smoking subjects DEV (right plus left lung) was 16% higher. No significant difference in VB between smokers and nonsmokers was found. The differences in DEV and VB between right and left lung were not significant. Mean values (+/- SD) of the dorsal-to-ventral ratios calculated for the right lung in the nonsmokers were as follows: DL, 1.34 +/- 0.16; VA, 0.90 +/- 0.05; VB, 1.52 +/- 0.26; DEV, 1.10 +/- 0.17; and Valv, 0.85 +/- 0.19. Almost identical ratios were found in the smokers. The influence of overall thoracic expansion was investigated in one subject restudied during voluntary hyperinflation and during positive end-expiratory pressure.     

Effects of hypergravity on the distributions of lung ventilation and perfusion in sitting humans assessed with a simple two-step maneuver.

Increased gravity impairs pulmonary distributions of ventilation and perfusion. We sought to develop a method for rapid, simultaneous, and noninvasive assessments of ventilation and perfusion distributions during a short-duration hypergravity exposure. Nine sitting subjects were exposed to one, two, and three times normal gravity (1, 2, and 3 G) in the head-to-feet direction and performed a rebreathing and a single-breath washout maneuver with a gas mixture containing C(2)H(2), O(2), and Ar. Expirograms were analyzed for cardiogenic oscillations (COS) and for phase IV amplitude to analyze inhomogeneities in ventilation (Ar) and perfusion [CO(2)-to-Ar ratio (CO(2)/Ar)] distribution, respectively. COS were normalized for changes in stroke volume. COS for Ar increased from 1-G control to 128 +/- 6% (mean +/- SE) at 2 G (P = 0.02 for 1 vs. 2 G) and 165 +/- 13% at 3 G (P = 0.002 for 2 vs. 3 G). Corresponding values for CO(2)/Ar were 135 +/- 12% (P = 0.04) and 146 +/- 13%. Phase IV amplitude for Ar increased to 193 +/- 39% (P = 0.008) at 2 G and 229 +/- 51% at 3 G compared with 1 G. Corresponding values for CO(2)/Ar were 188 +/- 29% (P = 0.02) and 219 +/- 18%. We conclude that not only large-scale ventilation and perfusion inhomogeneities, as reflected by phase IV amplitude, but also smaller-scale inhomogeneities, as reflected by the ratio of COS to stroke volume, increase with hypergravity. Except for small-scale ventilation distribution, most of the impairments observed at 3 G had been attained at 2 G. For some of the parameters and gravity levels, previous comparable data support the present simplified method.     

The lung diffusing capacity for nitric oxide in rats is increased during endotoxemia.

Rats, when injected with endotoxin, begin to exhale nitric oxide (NO) within 1 h. This study measured the diffusing capacity for NO in the lungs of rats (DL(NO)) under both control and endotoxemic conditions, and it also estimated the rate at which endogenous NO (VP(NO)) enters the distal compartment of the lung, both in control rats and during endotoxemia. DL(NO) increased from 0.68 +/- 0.12 (SE) ml. min(-1). mmHg(-1) in control rats to 1.17 +/- 0.25 ml. min(-1). mmHg(-1) in endotoxemic rats. VP(NO) was 2.6 +/- 0.5 nl/min in control rats and attained a value of 218.6 +/- 50.1 nl/min at the height of NO exhalation 3 h after the endotoxin. We suggest that increased DL(NO) reflects an increase in pulmonary membrane diffusing capacity, caused by a pulmonary hypertension that is due to neutrophil aggregation in the lung capillaries. DL(NO) may also be increased by an enlarged pulmonary capillary volume because of the vasodilatory effects of the endogenous NO that is produced by the lung in response to the endotoxin. NO production by the lungs in response to endotoxin is unique in that it is the only situation reported to date in which pathologically induced increases in NO exhalation originate from the alveolar compartment of the lung, as opposed to the small conducting airways.     

Pulmonary blood flow distribution measured by radionuclide-computed tomography

Distributions of pulmonary blood flow per unit lung volume were measured with subjects in the prone, supine, and sitting positions by means of radionuclide-computed tomography of intravenously administered 99mTc-labeled macroaggregates of human serum albumin. The blood flow was greater in the direction of gravity in all 31 subjects except one with severe mitral valve stenosis. With the subject in a sitting position, four different types of distribution were distinguished. One type had a three-zonal blood flow distribution as previously reported by West and co-workers (J. Appl. Physiol. 19: 713-724, 1964). Pulmonary arterial pressure and venous pressure estimated from this model showed reasonable agreement with pulmonary arterial pressure and capillary wedge pressure measured by Swan-Ganz catheter in 17 supine patients and in 2 sitting patients. The method makes possible noninvasive assessment of pulmonary vascular pressures.     

Chemiluminescent measurements of nitric oxide pulmonary diffusing capacity and alveolar production in humans.

Measurements of nitric oxide (NO) pulmonary diffusing capacity (DL(NO)) multiplied by alveolar NO partial pressure (PA(NO)) provide values for alveolar NO production (VA(NO)). We evaluated applying a rapidly responding chemiluminescent NO analyzer to measure DL(NO) during a single, constant exhalation (Dex(NO)) or by rebreathing (Drb(NO)). With the use of an initial inspiration of 5-10 parts/million of NO with a correction for the measured NO back pressure, Dex(NO) in nine healthy subjects equaled 125 +/- 29 (SD) ml x min(-1) x mmHg(-1) and Drb(NO) equaled 122 +/- 26 ml x min(-1) x mmHg(-1). These values were 4.7 +/- 0.6 and 4.6 +/- 0.6 times greater, respectively, than the subject's single-breath carbon monoxide diffusing capacity (Dsb(CO)). Coefficients of variation were similar to previously reported breath-holding, single-breath measurements of Dsb(CO). PA(NO) measured in seven of the subjects equaled 1.8 +/- 0.7 mmHg x 10(-6) and resulted in VA(NO) of 0.21 +/- 0.06 microl/min using Dex(NO) and 0.20 +/- 0.6 microl/min with Drb(NO). Dex(NO) remained constant at end-expiratory oxygen tensions varied from 42 to 682 Torr. Decreases in lung volume resulted in falls of Dex(NO) and Drb(NO) similar to the reported effect of volume changes on Dsb(CO). These data show that rapidly responding chemiluminescent NO analyzers provide reproducible measurements of DL(NO) using single exhalations or rebreathing suitable for measuring VA(NO).     

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.     

Hysteresis of the alveolar capillary membrane in normal subjects

Weibel and associates (Respir. Physiol. 18: 285-308, 1973), using morphometric techniques, demonstrated in the rat that changes in lung volume related to inflation and deflation caused a hysteretic variation in alveolar capillary membrane which is locally pleated at low pulmonary volume, unfolds during inflation but does not immediately refold during deflation, possibly enhancing the CO diffusion throughout the membrane. The present study was conducted to verify the existence of this hysteresis in human lungs in vivo. Single-breath diffusing capacity for CO (DLCO) was measured in five healthy seated subjects before and 0, 0.5, 1, 3, and 7 min after an inflation-deflation maneuver (IDM) in 6 separate days. The value of mean DLCO was 36.4 +/- 3 (SD) before and 42.1 +/- 2.9, 41.6 +/- 3.3, 40.3 +/- 3.3, 39.2 +/- 3.2, and 38.1 +/- 2.7 ml X min-1 X Torr-1 after the IDM. Two mechanisms can explain our findings: an active filling of the capillary bed, or an unfolding of the alveolar capillary membrane. The first mechanism should be accompanied by changes in pulmonary circulation. Therefore, right-heart catheterization was performed in two normal subjects and in four patients examined for a chest pain syndrome. At the end of the IDM, the values for the pulmonary artery pressure and capillary wedge pressure had returned to control levels. This suggests that the capillary bed is not directly involved in the DLCO increase observed from 0.5 to 7 min after the IDM. The unfolding of the alveolar capillary membrane appears to better explain our findings.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preventing mediastinal shift after pneumonectomy does not abolish physiological compensation.

To determine the role of mediastinal shift after pneumonectomy (PNX) on compensatory responses, we performed right PNX in adult dogs and replaced the resected lung with a custom-shaped inflatable silicone prosthesis. Prosthesis was inflated (Inf) to prevent mediastinal shift, or deflated (Def), allowing mediastinal shift to occur. Thoracic, lung air, and tissue volumes were measured by computerized tomography scan. Lung diffusing capacities for carbon monoxide (DL(CO)) and its components, membrane diffusing capacity for carbon monoxide (Dm(CO)) and capillary blood volume (Vc), were measured at rest and during exercise by a rebreathing technique. In the Inf group, lung air volume was significantly smaller than in Def group; however, the lung became elongated and expanded by 20% via caudal displacement of the left hemidiaphragm. Consequently, rib cage volume was similar, but total thoracic volume was higher in the Inf group. Extravascular septal tissue volume was not different between groups. At a given pulmonary blood flow, DL(CO) and Dm(CO) were significantly lower in the Inf group, but Vc was similar. In one dog, delayed mediastinal shift occurred 9 mo after PNX; both lung volume and DL(CO) progressively increased over the subsequent 3 mo. We conclude that preventing mediastinal shift after PNX impairs recruitment of diffusing capacity but does not abolish expansion of the remaining lung or the compensatory increase in extravascular septal tissue volume.     

Diffusing Capacity,Specific Diffusing Capacity and Interpretation of Diffusion Defects

Six pathophysiologic mechanisms of a reduced single breath CO diffusing capacity are discussed and the usefulness of relating carbon monoxide (CO) uptake to the functioning alveolar volume (DL/VA, specific diffusing capacity) is illustrated for several pulmonary diseases. In patients with emphysema and pulmonary emboli (pulmonary vascular occlusive disease), reduced CO uptake is associated with significantly reduced DL/VA and is compatible with reduction of pulmonary capillary bed. In patients with pulmonary alveolar proteinosis, improvement in CO uptake and DL/VA follows lung lavage and suggests that lung units partially filled with proteinaceous material are responsible for hypoxemia, reduced CO uptake and reduced DL/VA. In most cases of radiation fibrosis, sarcoidosis and miscellaneous interstitial fibrosis, reduced CO uptake is associated with a normal DL/VA and suggests that loss of alveolar units, both capillaries and alveoli, has occurred. New regression equations for DL and DL/VA are established for children and adults. DL/VA is linearly related to height and independent of age and sex, while different predictive equations must be used for DL for the 5 through 17 and 18 through 76 age groups. The new regression equations for DL show better correlation in adults we studied over 50 years of age than previous regression equations which use a constant reduction of 2 to 3 ml CO per minute per mm of mercury for each 10 years of adult aging.     

Lower pulmonary diffusing capacity in the prone vs. supine posture.

We evaluated the effect of prone positioning on gas-transfer characteristics in normal human subjects. Single-breath (SB) and rebreathing (RB) maneuvers were employed to assess carbon monoxide diffusing capacity (DlCO), its components related to capillary blood volume (Vc) and membrane diffusing capacity (Dm), pulmonary tissue volume (Vti), and cardiac output (Qc). Alveolar volume (Va) was significantly greater prone than supine, irrespective of the test maneuver used. Nevertheless, Dl(CO) was consistently lower prone than supine, a difference that was enhanced when appropriately corrected for the higher Va prone. When adequately corrected for Va, diffusing capacity significantly decreased by 8% from supine to prone [SB: Dl(CO,corr) supine vs. prone: 32.6 +/- 2.3 (SE) vs. 30.0 +/- 2 ml x min(-1) x mmHg(-1) stpd; RB: Dl(CO,corr) supine vs. prone: 30.2 +/- 2.2 (SE) vs. 27.8 +/- 2.0 ml x min(-1) x mmHg(-1) stpd]. Both Vc and Dm showed a tendency to decrease from supine to prone, but neither reached significance. Finally, there were no significant differences in Vti or Qc between supine and prone. We interpret the lower diffusing capacity of the healthy lung in the prone posture based on the relatively larger space occupied by the heart in the dependent lung zones, leaving less space for zone 3 capillaries, and on the relatively lower position of the heart, leaving the zone 3 capillaries less engorged.     

Short-term hypoxic exposure at rest and during exercise reduces lung water in healthy humans.

Hypoxia and hypoxic exercise increase pulmonary arterial pressure, cause pulmonary capillary recruitment, and may influence the ability of the lungs to regulate fluid. To examine the influence of hypoxia, alone and combined with exercise, on lung fluid balance, we studied 25 healthy subjects after 17-h exposure to 12.5% inspired oxygen (barometric pressure = 732 mmHg) and sequentially after exercise to exhaustion on a cycle ergometer with 12.5% inspired oxygen. We also studied subjects after a rapid saline infusion (30 ml/kg over 15 min) to demonstrate the sensitivity of our techniques to detect changes in lung water. Pulmonary capillary blood volume (Vc) and alveolar-capillary conductance (D(M)) were determined by measuring the diffusing capacity of the lungs for carbon monoxide and nitric oxide. Lung tissue volume and density were assessed using computed tomography. Lung water was estimated by subtracting measures of Vc from computed tomography lung tissue volume. Pulmonary function [forced vital capacity (FVC), forced expiratory volume after 1 s (FEV(1)), and forced expiratory flow at 50% of vital capacity (FEF(50))] was also assessed. Saline infusion caused an increase in Vc (42%), tissue volume (9%), and lung water (11%), and a decrease in D(M) (11%) and pulmonary function (FVC = -12 +/- 9%, FEV(1) = -17 +/- 10%, FEF(50) = -20 +/- 13%). Hypoxia and hypoxic exercise resulted in increases in Vc (43 +/- 19 and 51 +/- 16%), D(M) (7 +/- 4 and 19 +/- 6%), and pulmonary function (FVC = 9 +/- 6 and 4 +/- 3%, FEV(1) = 5 +/- 2 and 4 +/- 3%, FEF(50) = 4 +/- 2 and 12 +/- 5%) and decreases in lung density and lung water (-84 +/- 24 and -103 +/- 20 ml vs. baseline). These data suggest that 17 h of hypoxic exposure at rest or with exercise resulted in a decrease in lung water in healthy humans.     

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.     

Effects of posture on the venodilatory response to nitroglycerin

To determine the effects of posture on the venodilatory response to nitroglycerin (TNG), the change in forearm venous volume after inflation of an upper arm cuff to 30 mmHg above cuff zero (VV[30]) was measured during control conditions and after TNG (0.8 mg spray) in 18 healthy young volunteers in the supine position and the sitting position. VV[30] was 3.24 +/- 0.98 ml/100 ml arm in the supine position and 2.46 +/- 1.32 ml/100 ml arm in the sitting position. TNG increased VV[30] by 0.56 +/- 0.19 ml/100 ml arm in supine subjects, but by only 0.38 +/- 0.17 ml/100 ml arm in sitting subjects (P = 0.013). When limb volume was measured in the forearm and calf without using a cuff to produce venous congestion, the increase in limb volume with TNG was significantly greater in the sitting than in the supine position. Because the fall in both systolic and diastolic pressure and the rise in heart rate were significantly greater after TNG was administered in the sitting position, it is suggested that a greater reflex venoconstriction occurred in this posture, which antagonized the TNG-induced increase in venous distensibility. In the seated position, the effect of gravity more than compensated for the impaired venodilatory response to TNG. These results suggest that TNG causes a greater reduction in venous return to the heart when administered in the sitting position than in the supine position.     

Effect of blood flow on gas transport in a pulmonary capillary

The effects of blood velocity on gas transport within the alveolar region of lungs, and on the lung diffusing capacity DL have for many years been regarded as negligible. The present work reports on a preliminary, two-dimensional investigation of CO convection-diffusion phenomenon within a pulmonary capillary. Numerical simulations were performed using realistic clinical and morphological parameter values, with discrete circular red blood cells (RBCs) moving with plasma in a single capillary. Steady-state simulations with stationary blood (RBCs and plasma) were performed to validate the model by comparison with published data. Results for RBCs moving at speeds varying from 1.0 mm/s to 10 mm/s, and for capillary hematocrit (Ht) from 5% to 55%, revealed an increase of up to 60% in DL, as compared to the stationary blood case. The increase in DL is more pronounced at low Ht (less than 25%) and high RBC speed and it seems to be caused primarily by the presence of plasma. The results also indicate that capillary blood convection affects DL not only by improving the plasma mixing in the capillary bed but also by replenishing the capillary with fresh (zero concentration) plasma, providing an additional reservoir for the consumption of CO. Our findings cast doubt on the current belief that an increase in the lung diffusing capacity of humans (for instance, during exercising), with fixed hematocrit, can only be accomplished by an increase in the lung volume effectively active in the respiration process.     

Effect of gravity on chest wall mechanics.

Chest wall mechanics was studied in four subjects on changing gravity in the craniocaudal direction (G(z)) during parabolic flights. The thorax appears very compliant at 0 G(z): its recoil changes only from -2 to 2 cmH(2)O in the volume range of 30-70% vital capacity (VC). Increasing G(z) from 0 to 1 and 1.8 G(z) progressively shifted the volume-pressure curve of the chest wall to the left and also caused a fivefold exponential decrease in compliance. For lung volume <30% VC, gravity has an inspiratory effect, but this effect is much larger going from 0 to 1 G(z) than from 1 to 1.8 G(z). For a volume from 30 to 70% VC, the effect is inspiratory going from 0 to 1 G(z) but expiratory from 1 to 1.8 G(z). For a volume greater than approximately 70% VC, gravity always has an expiratory effect. The data suggest that the chest wall does not behave as a linear system when exposed to changing gravity, as the effect depends on both chest wall volume and magnitude of G(z).     

Exhaled nitric oxide and exercise performance in heart failure

BACKGROUND: In heart failure abnormalities of pulmonary function are frequently observed particularly during exercise, which is characterized by hyperpnea, low tidal volume, early expiratory flow limitation and reduced lung compliance. Exhaled nitric oxide (NO) is increased in asthma. We evaluated whether a correlation between exhaled NO and lung mechanics exists during exercise in heart failure. METHODS: We studied 33 chronic heart failure patients and 11 healthy subjects with: a) standard pulmonary function, b) lung diffusion for carbon monoxide (DLCO) including its subcomponents, capillary volume and membrane resistance and eNO both at rest and during light exercise, c) maximal cycloergometer cardiopulmonary exercise test. RESULTS: Forced expiratory volume in 1 second (FEV1) was reduced in heart failure patients (83 +/- 17% of predicted) as was DLCO (75 +/- 18% of predicted) due to reduced membrane resistance (32.6 +/- 10.3 ml/mmHg/min vs. 39.9 +/- 6.9 in patients vs. controls, p < 0.02). eNO was lower in patients vs. controls (9.7 +/- 5.4 ppm vs. 14.4 +/- 6.4, p < 0.05) and was, during exercise, constant in patients and reduced in controls. No significant correlation was found between eNO and lung function. Vice-versa eNO changes during exercise were correlated with peak exercise oxygen consumption (r = 0.560, p < 0.001). CONCLUSIONS: The hypothesis of a link between eNO and lung function in heart failure was not proved. The correlation between eNO changes during exercise and peak VO2 might be due to hemoglobin oxygenation which binds NO to hemoglobin.     

Continuous monitoring of blood volume changes in humans

The mass density of antecubital venous blood was measured continuously for 80 min/session with 0.1 g/l precision at a flow rate of 1.5 ml/min in six male subjects. Each person participated in two different sessions with the same protocol. To induce transvascular fluid shifts, the subjects changed from sitting to standing and from standing to supine positions. There was transient blood density shifts immediately after postural changes, followed by an asymptotic approach to a new steady-state blood density level. Additional deviations from a simple time course were regularly observed. Blood density increased by 3.5 +/- 1.4 (SD) g/l when standing after sitting and decreased by 5.0 +/- 1.2 g/l while supine after standing. The corresponding half time of the blood density increase was 5.6 +/- 1.4 min (standing after sitting) and 6.9 +/- 3.1 min (supine after standing) of the blood density decrease. Erythrocyte density was calculated and did not change with body position. Whole-body blood density was calculated from plasma density, hematocrit, and erythrocyte density, assuming an F-cell ratio of 0.91. Volume shifts were computed from the density data; the subject's blood volume density decreased by 6.2 +/- 1.2% from sitting to standing and increased by 8.5 +/- 2.1% from standing to supine. Additional discrete plasma density and hematocrit measurements gave linear relations (P less than 0.001) between all possible combinations of blood density, plasma density, and hematocrit.(ABSTRACT TRUNCATED AT 250 WORDS)