Long-term enhancement of pulmonary gas exchange after high-altitude residence during maturation.

In a previous study, our laboratory showed that young dogs born at sea level (SL) and raised from 2.5 mo of age to beyond somatic maturity at a high altitude (HA) of 3,100 m show enhanced resting lung function (Johnson RL Jr, Cassidy SS, Grover RF, Schutte JE, and Epstein RH. J Appl Physiol 59: 1773-1782, 1985). To examine whether HA-induced adaptation improves pulmonary gas exchange during exercise and whether adaptation is reversible when animals return to SL before somatic maturity, we raised 2.5-mo-old foxhounds at HA (3,800 m) for 5 mo (to age 7.5 mo) before returning them to SL. Lung function was measured under anesthesia 1 mo and 2 yr after return to SL and during exercise approximately 1 yr after return. In animals exposed to HA relative to simultaneous litter-matched SL controls, resting circulating blood and erythrocyte volumes, lung volumes, septal volume estimated by a rebreathing technique, and lung tissue volume estimated by high-resolution computed tomography scan were persistently higher. Lung diffusing capacity, membrane diffusing capacity, and pulmonary capillary blood volume estimated at a given cardiac output were significantly higher in animals exposed to HA, whereas maximal oxygen uptake and hematocrit were similar between groups. We conclude that relatively short exposure to HA during somatic maturation improves long-term lung function into adulthood.     

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.     

Functional capacities of lungs and thorax in beagles after prolonged residence at 3,100 m

Functional capacities of the lungs and thorax in beagles taken to high altitude as adults for 33 mo or in beagles raised from puppies at high altitude were compared with functional capacities in corresponding sets of beagles kept simultaneously at sea level. Comparisons were made after reacclimatization to sea level. Lung volumes, airway pressures, esophageal pressures, CO diffusing capacities (DLCO), pulmonary blood flow, and lung tissue volume (Vt) were measured by a rebreathing technique at inspired volumes ranging from 15 to 90 ml/kg. In beagles raised from puppies we measured anatomical distribution of intrathoracic air and tissue using X-ray computed tomography at transpulmonary pressures of 20 cm H2O. Lung and thoracic distensibility, DLCO, and Vt were not different between beagles that had been kept at high altitude for 33 mo as adults and control subjects kept simultaneously at sea level. Lung distensibility, DLCO, and Vt were significantly greater in beagles raised at high altitude than control subjects raised simultaneously at sea level. Thoracic distensibility was not increased in beagles raised at high altitude; the larger lung volume was accommodated by a lower diaphragm, not a larger rib cage.     

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.     

Pulmonary function of the green sea turtle, Chelonia mydas

Lung volumes, oxygen uptake (VO2), end-tidal PO2, and PCO2, diffusing capacity of the lungs for CO (DLCO), pulmonary blood flow (QL) and respiratory frequency were measured in the green sea turtle (Chelonia mydas) (49-127 kg body wt). Mean lung volume (VL) determined from helium dilution was 57 ml/kg and physiological dead space volume (VD) was about 3.6 ml/kg. QL, determined from acetylene uptake during rebreathing, increased in proportion to VO2 with temperature. Therefore, constant O2 content difference was maintained between pulmonary arterial and venous blood. DLCO, measured using a rebreathing technique, was 0.04 ml X kg-1 X min-1 X Torr-1 at 25 degrees C. Several cardiopulmonary characteristics in C. mydas are advantageous to diving: large tidal volume relative to functional residual capacity promotes fast exchange of the alveolar gas when the turtle surfaces for breathing: and the concomitant rise of pulmonary blood flow and O2 uptake with temperature assures efficient O2 transport regardless of wide temperature variations encountered during migrations.     

Pulmonary diffusing capacity and capillary blood volume in aging dogs.

Single-breath carbon monoxide diffusing capacity (DLco), pulmonary capillary blood volume (Vc), and membrane diffusing capacity (Dm) were measured in 24 beagle dogs aged 289-3,882 days. DLco and Vc were a function of age and alveolar volume (Va). Vc decreased with age resulting in changes in DLco. Changes in Vc may have been due to pulmonary morphological changes or to an exaggerated decrease in pulmonary blood flow in old dogs in response to 20-30 cmH-2O transpulmonary pressure. There was no age-related change in Dm.     

Residence at 3,800-m altitude for 5 mo in growing dogs enhances lung diffusing capacity for oxygen that persists at least 2.5 years.

Mammals native to high altitude (HA) exhibit larger lung volumes than their lowland counterparts. To test the hypothesis that adaptation induced by HA residence during somatic maturation improves pulmonary gas exchange in adulthood, male foxhounds born at sea level (SL) were raised at HA (3,800 m) from 2.5 to 7.5 mo of age and then returned to SL prior to somatic maturity while their littermates were simultaneously raised at SL. Following return to SL, all animals were trained to run on a treadmill; gas exchange and hemodynamics were measured 2.5 years later at rest and during exercise while breathing 21% and 13% O(2). The multiple inert gas elimination technique was employed to estimate ventilation-perfusion (Va/Q) distributions and lung diffusing capacity for O(2) (Dl(O(2))). There were no significant intergroup differences during exercise breathing 21% O(2). During exercise breathing 13% O(2), peak O(2) uptake and Va/Q distributions were similar between groups but arterial pH, base excess, and O(2) saturation were higher while peak lactate concentration was lower in animals raised at HA than at SL. At a given exercise intensity, alveolar-arterial O(2) tension gradient (A-aDo(2)) attributable to diffusion limitation was lower while Dlo(2) was 12-25% higher in HA-raised animals. Mean systemic arterial blood pressure was also lower in HA-raised animals; mean pulmonary arterial pressures were similar. We conclude that 5 mo of HA residence during maturation enhances long-term gas exchange efficiency and Dl(O(2)) without impacting Va/Q inequality during hypoxic exercise at SL.     

Noninvasive diffusing capacity and cardiac output in exercising dogs

We have developed a rebreathing procedure to determine diffusing capacity (DLCO) and pulmonary blood flow (Qc) in the awake, exercising dog. A low dead space, leak-free respiratory mask with an incorporated mouthpiece was utilized to achieve mixing between the rebreathing bag and the dog's lung. The rebreathing bag was initially filled with approximately 1.0 liter of gas containing 0.6% C2H2, 0.3% C18O, 9% He, and 35-40% O2. End-tidal gas concentrations were measured with a respiratory mass spectrometer. The disappearance of C2H2 and C18O was measured with respect to He to calculate Qc and DLCO. Values for DLCO in dogs, expressed per kilogram of body weight, were much larger than those reported in humans. However, at a given level of absolute O2 consumption, measurements of absolute DLCO in dogs were comparable to those reported in humans by both rebreathing and steady-state methods at rest and near-maximal exercise. These results suggest that DLCO is more closely matched to the metabolic capacity (i.e., maximal O2 consumption) than to body size between these two species.     

Temporal effects in the estimation of pulmonary diffusing capacity

Steady state estimates of the pulmonary diffusing capacity for carbon monoxide (DLCO) require measurement of the uptake and the average alveolar partial pressure of carbon monoxide (PACO). The expired alveolar sample obtained by different experimental methods and/or breathing patterns rarely represents the actual PACO. It is widely accepted that nonuniform distribution of ventilation, diffusion and perfusion causes discrepancies in the measurement of diffusing capacity. tan additional source of error in choosing PACO arises in the sampling time chosen by the experimental method. A theoretical study of a ramp-with-pause and a square breathing pattern demonstrates that the sample-time error exists even in the homogeneous lung. The study shows for the homogeneous lung that the correct fractional concentration of alveolar carbon monoxide (FAV) occurs at a time (TAV), one-half of a breathing period after the effective inspiration time (TI) for the two very different breathing patterns. TI is well-defined in relation to any breathing pattern which can be approximated by ramps and pauses. If TAV and the sample time chosen by the experimental method are known, then the measured DLCO can be corrected to the actual diffusing capacity (DL). The theory agrees with experimental results and computer simulations of inhomogeneous lungs from the literature. This agreement suggests that the theory for the homogeneous lung is also relevant to the inhomogeneous lung.     

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.     

Improvement in lung diffusion by endothelin A receptor blockade at high altitude

Lung diffusing capacity has been reported variably in high-altitude newcomers and may be in relation to different pulmonary vascular resistance (PVR). Twenty-two healthy volunteers were investigated at sea level and at 5,050 m before and after random double-blind intake of the endothelin A receptor blocker sitaxsentan (100 mg/day) vs. a placebo during 1 wk. PVR was estimated by Doppler echocardiography, and exercise capacity by maximal oxygen uptake (Vo(2 max)). The diffusing capacities for nitric oxide (DL(NO)) and carbon monoxide (DL(CO)) were measured using a single-breath method before and 30 min after maximal exercise. The membrane component of DL(CO) (Dm) and capillary volume (Vc) was calculated with corrections for hemoglobin, alveolar volume, and barometric pressure. Altitude exposure was associated with unchanged DL(CO), DL(NO), and Dm but a slight decrease in Vc. Exercise at altitude decreased DL(NO) and Dm. Sitaxsentan intake improved Vo(2 max) together with an increase in resting and postexercise DL(NO) and Dm. Sitaxsentan-induced decrease in PVR was inversely correlated to DL(NO). Both DL(CO) and DL(NO) were correlated to Vo(2 max) at sea level (r = 0.41-0.42, P < 0.1) and more so at altitude (r = 0.56-0.59, P < 0.05). Pharmacological pulmonary vasodilation improves the membrane component of lung diffusion in high-altitude newcomers, which may contribute to exercise capacity.     

A modeling approach to the estimation of CO diffusing capacity

Standard methods of measuring the diffusing capacity of the lung for CO are susceptible to inhomogeneity and to errors in the performance of a breathing maneuver by the subject. A mathematical model of CO uptake from a single alveolar lung is developed and used as the basis for an estimation procedure to measure both lung volume and diffusing capacity during a rebreathing maneuver. Because this estimator-model uses the exact flow generated by the subject, errors in such factors as breath-hold times or depth of inspiration do not result. The estimator-model was tested using simulated data from uniformly and nonuniformly ventilated models and was found to be insensitive to noise and inhomogeneity, in contrast to the diffusing capacity of the lungs for CO (exhaled). The estimator-model makes greater use of the available data than traditional methods by utilizing both the slope of the alveolar plateaus for CO and the relative heights of such plateaus in a rebreathing experiment.     

Evaluation of lung diffusing capacity by physiological and morphometric techniques

Determinations of pulmonary diffusing capacity for CO (DLCO) by physiological and morphometric techniques have resulted in substantially different values for both DLCO and its major components. To evaluate the differences in these methods of measurement of DLCO, measurements were made under controlled conditions on isolated perfused dog lungs. Multiple gas-rebreathing techniques were used to measure DLCO, the membrane component of the diffusing capacity for CO (DmCO), and pulmonary capillary blood volume (Vc) in both anesthetized dogs and after isolation and perfusion of their lungs. The isolated perfused lungs were than perfusion fixed for morphometric analysis of the components of DLCO. The values obtained morphometrically for Vc were similar to those measured by physiological techniques. Perfusion fixation did not substantially alter the morphometric estimate of DmCO when compared with previous values obtained on inflation fixed lungs. However, the morphometric estimate of DmCO was over 10 times higher than that estimated physiologically. Analysis of the potential errors in the techniques suggests that the correct value for DmCO is substantially higher than that commonly estimated by use of physiological techniques and that the explanation for the difference is due to a number of factors that can influence the binding of CO to hemoglobin under in vivo conditions. The net effect of these factors can be represented by an unknown in each component of the Roughton-Forster relationship so that 1/DL = 1/(U1.Dm) + 1/(U2.theta Vc), where theta is the binding rate for CO to hemoglobin. Because the magnitudes of the unknown terms (U1 and U2) in the Roughton-Forster relationship are likely to be large, this relationship cannot be reliably used to determine Dm and Vc.     

Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy.

To determine whether all-trans retinoic acid (RA) treatment enhances lung function during compensatory lung growth in fully mature animals, adult male dogs (n = 4) received 2 mg x kg(-1) x day(-1) po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls (n = 4) received placebo. After 3 mo, transpulmonary pressure (TPP)-lung volume relationship, diffusing capacities for carbon monoxide and nitric oxide, cardiac output, and septal volume (V(tiss-RB)) were measured under anesthesia by a rebreathing technique at two lung volumes. Lung air and tissue volumes (V(air-CT) and V(tiss-CT)) were also measured from high-resolution computerized tomographic (CT) scans at a constant TPP. In RA-treated dogs compared with controls, TPP-lung volume relationships were similar. Diffusing capacities for carbon monoxide and nitric oxide were significantly impaired at a lower lung volume but similar at a high lung volume. Whereas V(tiss-RB) was significantly lower at both lung volumes in RA-treated animals, V(air-CT) and V(tiss-CT) were not different between groups; results suggest uneven distribution of ventilation consistent with distortion of alveolar geometry and/or altered small airway function induced by RA. We conclude that RA does not improve resting pulmonary function during the early months after R-PNX despite histological evidence of its action in enhancing alveolar cellular growth in the remaining lung.     

Prediction of carbon monoxide diffusing capacity of the lung in splenectomized sheep.

The steady state diffusing capacity of the lung for carbon monoxide (DLCO) was studied in 18 splenectomized adult ewes. Seven animals were anemic when studied. Weight (Wt) and, to a lesser extent, hemoglobin (Hb) level were the key predictive variables of DLCO. Sheep DLCO can be expected to range between 15 and 28 ml/min/mmHg in adult ewes which are not anemic. When DLCO measurements were repeated up to three times on the same day no significant decreases occurred. Thus, the data demonstrated no CO back-pressure caused by preceding DLCO determinations. This paper's importance is in defining a normal predictive range for this sensitive parameter of pulmonary function.     

Saturation kinetics for steady-state pulmonary CO transfer

Steady-state diffusing capacity of the lungs for carbon monoxide (DLCO) was measured in 13 anesthetized, paralyzed dogs ventilated at constant tidal volume and rate, using four different inspired CO levels (190, 600, 1,110, and 2,000 ppm). DLCO increased and reached a maximum as the inspired CO level was raised from 190 to 600 ppm. Further increases in inspired CO concentration were accompanied by a decrease in inspired CO concentration were accompanied by a decrease in DLCO. CO dead space and Pao2 remained constant at all inspired O2 levels. In some experiments a second set of measurements was made, the results of which were similar to those of the first set. The results cannot be explained by changes in CO back pressure, pulmonary capillary volume, or reaction rate of CO with hemoglobin, but can be explained if there is carrier-mediated CO transport in the alveolar capillary membrane.     

Effect of ventilation and perfusion imbalance on inert gas rebreathing variables

The effects of ventilation-to-perfusion (VA/Qc) maldistribution within the lungs on measured multiple gas rebreathing variables were studied in 14 dogs. The rebreathing method (using He, C18O, and C2H2) allows for measurements of pulmonary capillary blood flow (Qc), diffusing capacity (DLco), lung gas volume, and the combined pulmonary tissue and capillary blood volume (VTPC). VA/Qc imbalance was created by reversibly occluding the right main pulmonary artery or by reversibly obstructing the left main bronchus in eight dogs. Six additional dogs were ventilated with 10 cmH2O positive end-expiratory pressure (PEEP) to create a bimodal distribution of VA/Qc within the lungs. No significant alterations in computed rebreathing variables, except for a small (14%) decrease in DLco, occurred during right main pulmonary artery occlusion, whereas obstruction of the left main bronchus caused parallel decreases (mean of 46%) in all rebreathing variables. Ventilation with 10 cmH2O PEEP for 3 h caused no alterations in VTPC when compared with postmortem determinations of total lung water. Thus marked alterations in distribution of Qc or creation of VA/Qc maldistributions with PEEP caused no significant changes in rebreathing parameters, whereas obstruction of the left main bronchus resulted in decreases in all rebreathing values consistent with the presumed size of the ventilation defect. Thus it appears that rebreathing estimates of VTPC and other rebreathing parameters are accurate in states of moderate VA/Qc maldistribution within the lung.     

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.     

Small-sample reproducibility estimates: an example using rebreathing measurements

We developed a statistical technique to estimate the reproducibility of a parameter from a population in which only two repeated measurements can be made in a single individual. The following data were analyzed: acetylene cardiac output (Qc), lung tissue volume (Vti), and carbon monoxide diffusing capacity (DLCO) measured by rebreathing techniques in a population of 86 healthy subjects (51 men and 35 women). Each subject was measured twice with a computerized rebreathing system using a test gas of 10% He-0.3% C18O-0.7% C2H2-25% O2-balance N2 while sitting at rest. The estimated coefficients of variation for repeated measurements were 6.8, 10.3, and 5.7% for Qc, Vti, and DLCO, respectively. Chebyshev's inequality was used to estimate the imprecision for a single measurement of these parameters and for averages of two or more repeated values. A single measurement of Qc would be within 14.2% of a "true" mean 90% of the time, whereas an average of three consecutive measurements would be within 8.2% of the true mean 90% of the time. Single measurements of Vti and DLCO were found to be within 21.7 and 12.0%, respectively, of the true mean 90% of the time. When three consecutive measurements are averaged, Vti is within 12.6% and DLCO is within 6.9% of the true mean 90% of the time. We conclude that 1) rebreathing Qc is as reproducible as other measurements of cardiac output, 2) rebreathing measurements of DLCO are as reproducible as those made by the single-breath technique, and 3) an average of two to three measurements of Vti should be made to obtain values with a reasonable degree of precision.     

Quantification of pulmonary vascular occlusion in dogs by use of the diffusing capacity

The purpose of these experiments was to quantify stagnant intrapulmonary blood caused by a pulmonary arterial occlusion (PAO). The hypothesis was that the diffusing capacity of the lung for CO (DLCO) would be altered little by PAO when measured with the usual inspired concentrations (0.3%) of CO, since stagnant blood distal to the occlusion takes up CO for 20 s or more before significant CO backpressure would develop. However, higher levels of CO (i.e., greater than or equal to 3%) would equilibrate faster with capillary blood (within 5-10 s), and DLCO measured 10-20 s subsequent to the high CO exposure would reflect only the DLCO in the unoccluded regions. Thus the fractional reduction in DLCO measured with 3% CO, with respect to that measured with 0.3% CO, should be related to the fractional occlusion of the pulmonary artery in a predictable way. We occluded the right pulmonary artery (RPAO), the left pulmonary artery (LPAO), or the left lower lobar artery (LLPAO) and found that DLCO measured during rebreathing a 0.3% CO mixture was 80, 87, and 94%, respectively, of the preocclusion value, whereas the DLCO measured during rebreathing a 3.3% CO mixture was 59, 73, and 87% of the preocclusion value. A computer model was developed to predict the reduction in DLCO at different levels of CO exposure that would be caused by varying fractions of PAO. Our data indicated that RPAO corresponded to a 42% vascular occlusion, LPAO a 35% occlusion, and LLPAO a 20% occlusion. Measurement of DLCO using low and high concentrations of CO might be useful in assessing the fraction of vascular bed occluded and in following noninvasively the course of vascular occlusion in a variety of pulmonary diseases.