Diffusing Capacity For O2 Research Articles

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.

Reducing lung strain after pneumonectomy impairs oxygen diffusing capacity but not ventilation-perfusion matching.

After pneumonectomy (Pnx), mechanical strain on the remaining lung is an important signal for adaptation. To examine how mechanical lung strain alters gas exchange adaptation after Pnx, we replaced the right lung of adult dogs with a custom-shaped inflatable silicone prosthesis. The prosthesis was kept 1) inflated (Inf) to reduce mechanical strain of the remaining lung and maintain the mediastinum in the midline, or 2) deflated (Def) to allow lung strain and mediastinal shift. Gas exchange was studied 4-7 mo later at rest and during treadmill exercise by the multiple inert gas elimination technique while animals breathed 21 and 14% O2 in balanced order. In the Inf group compared with Def group during hypoxic exercise, arterial O2 saturation was lower and alveolar-arterial O2 tension difference higher, whereas O2 diffusing capacity was lower at any given cardiac output. Dispersion of the perfusion distribution was similar between groups at rest and during exercise. Dispersion of the ventilation distribution was lower in the Inf group at rest, associated with a much higher respiratory rate, but rose to similar levels in both groups during hypoxic exercise. Mean pulmonary arterial pressure at a given cardiac output was higher in the Inf group, whereas peak cardiac output was similar between groups. Thus creating lung strain by post-Pnx mediastinal shift primarily enhances diffusive gas exchange with only minor effects on ventilation-perfusion matching, consistent with the generation of additional alveolar-capillary surfaces but not conducting airways and blood vessels.

Skeletal muscle capillary hemodynamics from rest to contractions: implications for oxygen transfer.

Muscle contractions evoke an immediate rise in blood flow. Distribution of this hyperemia within the capillary bed may be deterministic for muscle O(2) diffusing capacity and remains unresolved. We developed the exteriorized rat (n = 4) spinotrapezius muscle for evaluation of capillary hemodynamics before (rest), during, and immediately after (post) a bout of twitch contractions to resolve (second-by-second) alterations in red blood cell velocity (V(RBC)) and flux (f(RBC)). Contractions increased (all P < 0.05) capillary V(RBC) (rest: 270 +/- 62 microm/s; post: 428 +/- 47 microm/s), f(RBC) (rest: 22.4 +/- 5.5 cells/s; post: 44.3 +/- 5.5 cells/s), and hematocrit but not the percentage of capillaries supporting continuous RBC flow (rest: 84.0 +/- 0.7%; post: 89.5+/-1.4%; P > 0.05). V(RBC) peaked within the first one or two contractions, whereas f(RBC) increased to an initial short plateau (first 12-20 s) followed by a secondary rise to steady state. Hemodynamic temporal profiles were such that capillary hematocrit tended to decrease rather than increase over the first approximately 15 s of contractions. We conclude that contraction-induced alterations in capillary RBC flux and distribution augment both convective and diffusive mechanisms for blood-myocyte O(2) transfer. However, across the first 10-15 s of contractions, the immediate and precipitous rise in V(RBC) compared with the biphasic and prolonged increase of f(RBC) may act to lower O(2) diffusing capacity by not only reducing capillary transit time but by delaying the increase in the instantaneous RBC-to-capillary surface contact thought crucial for blood-myocyte O(2) flux.

Effects of crocetin on pulmonary gas exchange in foxhounds during hypoxic exercise.

The carotenoid compound crocetin has been hypothesized to enhance the diffusion of O(2) through plasma, and observations in the rat and rabbit have revealed improvement in arterial PO(2) when crocetin is given. To determine whether crocetin enhances diffusion of O(2) between alveolar gas and the red blood cell in the pulmonary capillary in vivo, five foxhounds, two previously subjected to sham and three to actual lobectomy or pneumonectomy, were studied while breathing 14% O(2) at rest and during moderate and heavy exercise before and within 10 min after injection of a single dose of crocetin as the trans isomer of sodium crocetinate (TSC) at 100 microg/kg iv. This dose is equivalent to that used in previous studies and would yield an initial plasma concentration of 0.7-1.0 microg/ml. Ventilation-perfusion inequality and pulmonary diffusion limitation were assessed by the multiple inert gas elimination technique in concert with conventional measurements of arterial and mixed venous O(2) and CO(2). TSC had no effect on ventilation, cardiac output, O(2) consumption, arterial PO(2)/saturation, or pulmonary O(2) diffusing capacity. There were minor reductions in ventilation-perfusion mismatching (logarithm of the standard deviation of perfusion fell from 0.48 to 0.43, P = 0.001) and in CO(2) output and respiratory exchange ratio (P = 0.05), which may have been due to TSC or to persisting effects of the first exercise bout. Spectrophotometry revealed that TSC disappeared from plasma with a half time of approximately 10 min. We conclude that, in this model of extensive pulmonary O(2) diffusion limitation, TSC as given has no effect on O(2) exchange or transport. Whether the original hypothesis is invalid, the dose of TSC was too low, or plasma diffusion of O(2) is not rate limiting without TSC cannot be discerned from the present study.

Perfusion, diffusion and their heterogeneities limiting blood-tissue O2 transfer in muscle.

The relative roles of blood flow (perfusion) and diffusion in O2 supply to exercising muscle can be estimated using a simple model consisting of an O2-consuming tissue block in contact with blood (perfusion Q, slope of O2 equilibirum curve beta) through a resistance to O2 diffusion (O2-diffusing capacity D). The decisive variable is the 'equilibration index' Y=D/(Qbeta). With decreasing Y, diffusion limitation increases and perfusion limitation decreases (Y > 3 indicates predominant perfusion limitation; 3 > Y > 0.1, combined perfusion and diffusion limitation, Y < 0.1, prevailing diffusion limitation). On the basis of literature data on humans at maximum O2 uptake, O2 supply to muscle is shown to be always limited by both perfusion and diffusion. In nomoxia, perfusion limitation is prevalent, but in hypoxia diffusion limitation becomes predominant. The underlying model assumes perfect homogeneity of muscles with respect to O2 requirement, diffusion conditions and blood flow. In numerous studies on isolated and in situ muscles a pronounced heterogeneity of blood flow has been found, also during exercise and at maximal O2 uptake. It is shown that with unequal distribution of blood flow and/or O2-diffusing capacity the efficiency of O2 transfer is reduced with reference to the homogeneous model. Therefore, the diffusing capacity value calculated on the basis of the homogeneous model is an underestimate of the true diffusing capacity and diffusion limitation is overestimated.

Effects of Skeletal Muscle Sarcomere Length onin VivoCapillary Distensibility

The structural integrity of the capillary wall is such that capillary luminal distensibility is largely determined by support provided by the tissue in which it is located. Given that O2flux density is greatest across the skeletal muscle capillary endothelium, any changes in capillary diameter (dc) would be expected to affect O2diffusing capacity as well as hemodynamic resistance. We used intravital microscopy techniques to study the maximally vasodilated rat (n= 5) spinotrapezius muscle microcirculationin vivowithin the physiological sarcomere length range, at high and low mean arterial pressures (MAP) systematically altered by blood withdrawal and infusion. We tested the hypothesis thatin vivocapillary diameter alterations in response to changes of MAP would be reduced at extended sarcomere lengths. At 2.4-μm sarcomere length, meandc(dc) within the spinotrapezius increased from 5.6 ± 0.1 to 5.9 ± 0.1 μm (P< 0.01) as MAP increased from 33 to 94 mm Hg. However, there was absolutely no change (i.e., 5.2 ± 0.1 vs 5.2 ± 0.1 μm) indcin response to changes in MAP at 3.2-μm sarcomere length. Furthermore, at sarcomere lengths <2.8 μm there was a significant increase (P< 0.01) indc(n= 40) as MAP increased, whereasdc(n= 49) remained unchanged with alterations of MAP when sarcomere length was ≥2.8 μm (P> 0.05). These data suggest that pressure-induced alterations in capillary luminal diameter and thus “in vivocapillary distensibility” are dependent upon the presiding sarcomere length. Furthermore, we conclude that the MAP-induced increases in capillary luminal diameter at the shorter sarcomere lengths are modest (∼5%) and unlikely to affect O2diffusing capacity and vascular resistance appreciably.

Dependence of oxygen uptake on ambient PO2 in isolated perfused frog skin.

Rates of O2 uptake across isolated perfused skin of bullfrogs (Rana catesbeiana) were measured in relation to blood flow at three levels of ambient O2 tension: normoxia (O2 tension = 152 torr), hypoxia (12% O2, 87 torr) and hyperoxia (42% O2, 306 torr). At bulk perfusion rates ranging from 3.4 to 10.1 microliters.cm-2 x min-1, O2 uptake was positively correlated with hemoglobin delivery rate in both normoxia and hyperoxia, but was independent of delivery rate in hypoxia. Mean O2 uptake in normoxia was 3.8 nmol O2 x cm-2 x min-1 at a delivery rate of 9.8 nmol.cm-2 x min-1 and 6.5 nmol O2 x cm-2 x min-1 at a delivery rate of 28.3 nmol.cm-2 x min-1. At any given bulk perfusion rate, oxygen uptake averaged about 49% lower in hypoxia than in normoxia, decreasing in proportion to the reduction of O2 tension difference between medium and blood. In hyperoxia, O2 uptake did not increase proportionally with the difference in O2 tension between blood and medium, averaging only 50% higher at a 2.4-fold greater O2 tension difference. Cutaneous diffusing capacity for O2 averaged 0.041 nmol O2 x cm-2 x torr-1 x min-1 during the first hour of perfusion in normoxia, and was not affected by reduction of ambient O2 tension. The results indicate that cutaneous O2 uptake in hypoxia is highly diffusion limited, and consequently, increases in cutaneous perfusion can not effectively compensate for reduction of ambient O2 tension. In hyperoxia, O2 uptake may be substantially perfusion limited because of reduced blood O2 capacitance at high O2 saturations.

The controversy about blood-gas CO2 equilibrium in lungs: reinvestigation by prolonged CO2 rebreathing in awake dogs during rest and exercise.

When pulmonary diffusing capacity for O2 is to be determined in lungs with unequal distribution of alveolar ventilation to pulmonary perfusion it is common practice to correct arterial PO2 for the shunt effect and the end-tidal PO2 for alveolar dead space ventilation. The latter correction is based on the assumption that PCO2 in end-capillary blood is in equilibrium with alveolar gas (Riley and Cournand, 1949). It appears to follow from this assumption that in conditions of no gas exchange, such as rebreathing, PCO2 in alveolar gas should be equal to that in arterial blood. Thus the finding of negative blood-to-gas PCO2 differences during rebreathing in dogs (Gurtner et al., 1969) and in man (Jones et al., 1969, 1972; Denison et al., 1971) has challenged the fundamental concepts of pulmonary gas exchange. However, these results could not be reproduced by others (Scheid et al., 1972).KeywordsPulmonary Diffuse CapacityRespiratory MassArterial PC02Rebreathing PeriodBlood PC02These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Oxygen transport in guinea pigs native to high altitude (Junin, Peru, 4,105 m).

In guinea pigs native to high altitude in the Andes (Peru) the arterial and mixed-venousP O 2,P CO 2, pH, and O2 content were measured at high altitude during breathing ambient air. Identical measurements were done in Nijmegen, The Netherlands, on sea-level natives and on guinea pigs exposed for 4–5 weeks to simulated altitude in a low pressure chamber, while breathing ambient air (normoxia) or an hypoxic mixture of O2 in N2 with aP I O 2 similar to that of the ambient air at high altitude. A standard blood O2 dissociation curve (ODC) was estimated in vitro (at pH=7.4 and 37.5°C), and a standard in vivo ODC was derived from measuredP O 2,S O 2 and pH in all three groups. Both guinea pigs native to natural or simulated high altitude had a higher hematocrit and blood O2 capacity than sea-level controls. These increased altitude values were, however, almost the same as the sea-level values of man or rat. No difference in the ideal alveolararterialP O 2 difference or lung diffusing capacity for O2 was found between (natural or simulated) high altitude animals and their corresponding controls, when measured at hypoxia. Mixed-venousP O 2 was higher in guinea pigs from the natural high altitude (but not in those from the low pressure chamber) when compared with control sea-level natives studied at hypoxia. No difference among groups in cardiac output was found, while breathing the same inspiratory mixture. In the guinea pigs native to high altitude a higher P50 and a lower Hill numbern for the in vitro ODC were found when compared with the controls or with the guinea pigs exposed to simulated high altitude. This was not observed when the ODC's were estimated in vivo. The rather modest polycythemic response to high altitude in guinea pigs coincides with a low value of P50, when related to body weight. In this respect the guinea pig seems to be more closely related to the typical high altitude mammals like Andean camelids and rodents than to man or rat that respond to high altitude with a pronounced polycythemia and possess a rather high P50 with respect to body weight.

Pulmonary O2-diffusing capacity in man by rebreathing: recent advances.

Pulmonary O2-diffusing capacity in man by rebreathing: recent advances.

Measurement of mixed venous oxygen tension by a modified rebreathing procedure.

ArticleMeasurement of mixed venous oxygen tension by a modified rebreathing procedure.P Cerretelli, P E Di Prampero, and D W RennieP Cerretelli, P E Di Prampero, and D W RenniePublished Online:01 May 1970https://doi.org/10.1152/jappl.1970.28.5.707MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByA rebreathing method for estimating pulmonary Do2: Theory and measurements in dog lungsRespiration Physiology, Vol. 18, No. 1Effects of cardiac output on 18O2 lung diffusion in normal resting manRespiration Physiology, Vol. 16, No. 3Estimation of the pulmonary diffusing capacity for O2 by a rebreathing procedureRespiration Physiology, Vol. 12, No. 2 More from this issue > Volume 28Issue 5May 1970Pages 707-11 https://doi.org/10.1152/jappl.1970.28.5.707PubMed5442266History Published online 1 May 1970 Published in print 1 May 1970 Metrics

Die O2-Diffusionskapazität der Lunge wacher Ziegen vor und während chronischer Anämie

The O2 diffusion capacity of the lungs was studied in unanesthetised goats before and during chronic anemia (Hematocrit 50% of normal). On the average, the diffusion capacity with a cardiac output of 5 l/min was 30% lower in anemic goats than in normal goats.

O2 diffusion in lung of the anesthetized cat

In cats under chloralose anesthesia, the mean diffusing capacity for O2 (Do2) was 0.91 (S.D. ± 0.29). The mean Do2/m2 body surface was 3.26 (S.D. ± 1.30). Under the experimental conditions described, the Do2 was linearly related to the O2 consumption/body weight or surface area of the animal. The Do2 was reduced by bronchial occlusion in approximate proportion to the blocked area. Cooling the animal also reduced the Do2. Epinephrine and 5-hydroxytryptamine given by constant intravenous infusion had slight effects on the Do2. Dissociation curves for cats' blood are reported. Submitted on December 5, 1958

A theoretical analysis of the alveolar-arterial O2 difference with special reference to the distribution effect.

SPECIAL COMMUNICATIONSA Theoretical Analysis of the Alveolar-Arterial O2 Difference With Special Reference to the Distribution EffectL. E. Farhi, and H. RahnL. E. Farhi, and H. RahnPublished Online:01 May 1955https://doi.org/10.1152/jappl.1955.7.6.699MoreSectionsPDF (850 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByFrom metabolism and behavior to respiratory physiology: an educational and research perspectiveEvelyn Heymann Schlenker3 September 2020 | Advances in Physiology Education, Vol. 44, No. 4Alveolar Air and O2 Uptake During Exercise in Patients With Heart FailureJournal of Cardiac Failure, Vol. 24, No. 10Hepatopulmonary Disorders: Gas Exchange and Vascular Manifestations in Chronic Liver Disease25 March 2018Alveolar air and oxidative metabolic demand during exercise in healthy adults: the role of single-nucleotide polymorphisms of the β2 AR gene23 October 2017 | Physiological Reports, Vol. 5, No. 20Pro: Hypoxic Pulmonary Vasoconstriction Is a Limiting Factor of Exercise at High AltitudeHigh Altitude Medicine & Biology, Vol. 12, No. 4Variability of indices of hypoxemia in adult respiratory distress syndromeCritical Care Medicine, Vol. 25, No. 1Pulmonary gas exchange during hypoxic exercise in the ratRespiration Physiology, Vol. 96, No. 2-3Hypoxic pulmonary vasoconstriction and pulmonary gas exchange in normal manRespiration Physiology, Vol. 68, No. 1Pulmonary function testing: Custom programs for manual equipmentComputers in Biology and Medicine, Vol. 14, No. 1Effect of shifts of the O2 dissociation curve upon alveolar-arterial O2 gradients in computer models of the lung with ventilation-perfusion mismatcingRespiration Physiology, Vol. 45, No. 2Analysis of chorioallantoic gas exchange in the chick embryoRespiration Physiology, Vol. 39, No. 3Distributions of V̇A/Q̇ in dog lungs obtained with the 50 compartment and the log normal approachRespiration Physiology, Vol. 38, No. 3Theoretical analysis of independent V̇a and Q̇ inequalities upon pulmonary gas exchangeRespiration Physiology, Vol. 29, No. 2Pulmonary gas exchange in dogs ventilated with mixtures of oxygen with various inert gasesRespiration Physiology, Vol. 28, No. 1The components of the alveolar-arterial oxygen tension difference in normal subjects and in patients with pneumonia and obstructive lung diseaseThe American Journal of Medicine, Vol. 52, No. 6Inhomogeneity effects on O2 and CO pulmonary diffusing capacity estimates by steady-state methods. TheoryRespiration Physiology, Vol. 13, No. 1A new lung model: An investigation with the aid of a digital computerComputers and Biomedical Research, Vol. 3, No. 3Pulmonary arteriovenous admixtureThe American Journal of Surgery, Vol. 119, No. 4Effect of slope and shape of dissociation curve on pulmonary gas exchangeRespiration Physiology, Vol. 8, No. 1Ventilation-perfusion inequality and overall gas exchange in computer models of the lungRespiration Physiology, Vol. 7, No. 1Apparent increase of the O2 diffusing capacity with increased O2 uptake in inhomogeneous lungs: TheoryRespiration Physiology, Vol. 6, No. 2Cirrhosis, cyanosis and polycythaemia: Multiple pulmonary arteriovenous anastomosesThe American Journal of Medicine, Vol. 45, No. 1Alveolar ventilation, diffusing capacity and the A-a Po2, difference in the newborn infantRespiration Physiology, Vol. 4, No. 2Alveolar-arterial O2 and CO2 pressure differences in the anesthetized, artificially ventilated dogRespiration Physiology, Vol. 3, No. 2Pulmonary diffusing capacity for oxygen in the anesthetized, artificially ventilated dog1Respiration Physiology, Vol. 3, No. 2VENOUS/ARTERIAL PULMONARY SHUNTING AS THE PRINCIPAL CAUSE OF POSTOPERATIVE HYPOXÆMIAThe Lancet, Vol. 289, No. 7480Causes of arterial hypoxemia in patients with obstructive pulmonary emphysemaThe American Journal of Medicine, Vol. 39, No. 3BLOOD-FLOW, VENTILATION, AND GAS EXCHANGE IN THE LUNGThe Lancet, Vol. 282, No. 7316Alveolar-arterial gas tension relationships in acute anterior poliomyelitisThe American Journal of Medicine, Vol. 30, No. 6 More from this issue > Volume 7Issue 6May 1955Pages 699-703 https://doi.org/10.1152/jappl.1955.7.6.699PubMed14381350History Published online 1 May 1955 Published in print 1 May 1955 Metrics

‘Ideal’ Alveolar Air and the Analysis of Ventilation-Perfusion Relationships in the Lungs

<i>‘Ideal’ Alveolar Air and the Analysis of Ventilation-Perfusion Relationships in the Lungs</i>