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Previous publications from this laboratory have described (1, 2) a modification of the Krogh breath holding technique for measuring the pulmonary diffusing capacity for carbon monoxide (DL).6 This test can be performed quickly and simply and does not require arterial blood analyses. It has recently (2) been shown to provide an index of pulmonary diffusing capacity similar to that given by the DLo2 method of Lilienthal, Riley, Proemmel, and Franke (3) and the "steady state" method of Filley, MacIntosh, and Wright (4). 6 Since the combination of CO with intracellular hemoglobin occurs at a rate that offers an appreciable, and under some conditions the major, part of the resistance to the uptake of CO in the lungs (5, 6) it is desirable to distinguish between the "true" diffusing capacity, or that of the pulmonary capillary membrane alone (D.), and the apparent diffusing capacity of the whole lung (DL). These are related by the equation 1/DL = I/D. + I/)Vc where j is the rate of combination of CO with intracorpuscular hemoglobin in ml. per min. per mm. Hg CO tension per ml. blood, and Vo is the volume of blood in the pulmonary capillaries at any instant. 0 decreases as 0 tension increases (7), causing DL to decrease, since D.and Ve are presumably relatively independent of alveolar 0, tension (8). Normally a further subscript of CO or Q, would be used to indicate the gas to which the measurement applies. However, in this article, which is mainly concerned with CO, the subscript is omitted and can be assumed to be "CO" unless otherwise stated. normal values of DL as well as values in patients with various chest diseases. METHODSThe technique for the measurement of DL, which has been reported be'fore (1, 2), consists essentially of having the subject make a maximal inspiration of a gas mixture containing 10 per cent helium (He), 0.3 per cent CO and approximately 21 per cent 02 in N2 from the level of his residual volume, hold it for a measured time, and then rapidly expire. All of this expiration except the first liter is collected in a bag by the operator and analyzed as alveolar gas. The CO concentration which was present in this sample before any CO The apparatus used for the test is illustrated in Figure 1. It differs from that reported previously (1, 2) mainly in its greater simplicity; in these previous communications the expired alveolar He and/or CO concentrations were measured at the mouth by recording analytical instruments. The circuit is closed, permitting inspiration from the bag of the Donald-Christie apparatus and expiration into the space around the bag, a spirometer recording the change in respiratory volumes. Tap (A) is used by the operator for collecting the expired alveolar sample. Since the gas mixture is inspired from the level

Numerous publications have considered the effects of inspiring high concentrations of CO on the venous blood carboxyhemoglobin concentration [COHb] in man (14). It appears, however, that no previous study has considered the physiological variables that determine [COHb] under conditions where inspired air CO concentrations are in the normal range. It has become apparent in recent years that CO is endogenously produced in normal man as a by-product of hemoglobin catabolism (and probably other hemoproteins as well) and therefore that the body CO stores are influenced by endogenous as well as exogenous CO (5,6). The development of a method of measuring the rate of endogenous CO production (Vco) in man (6) has made it possible to study the relationship of Vco and other variables to [COHb]. This is of particular interest since the latter has been used as an index of hemolysis (7). The Vco has been shown to reflect quantitatively the rate of circulating erythrocyte hemoglobin destruction in normal subjects (8) and in patients with hemolytic anemia (9), and the accuracy of this index would depend on how closely [COHb] reflects Vco.In this paper we have developed equations that appear to describe the major physiological variables that determine blood [COHb] have applied these equations to data obtained from a) normal subjects, b) male volunteers who breathed 100% oxygen for extended periods of time, and c) patients with elevated rates of endogenous CO production. MethodsAir CO measurements. Samples of air taken from the "wards" of the Hospital of the University of Pennsylvania were analyzed for CO concentrations with an infrared CO meter. This instrument has an error (SD) of 4-0.00004% CO and requires a 200-ml sample. These samples were collected during the summer of 1964. Smoking is prohibited in the areas where these samples were collected. We also measured the CO concentrations in air samples taken from smoke-filled conference rooms, a small nonventilated room that we purposely filled with smoke by burning cigarettes, and a rural area well away from automobile combustion. Diurnal changes in blood [COHb] were measured in one subject and compared with the changes in percentage of CO in his environment. Blood [COHb] was determined by a method in which gas extracted from a 2-ml blood sample is measured in the infrared CO meter. This method has an error (SD) of 40.03% [COHb]( 10).Washout experiments. Three normal young male subjects breathed 100% oxygen for 4 to 8 hours. The subjects were seated, wore a noseclip, and breathed the oxygen through a mouthpiece using an open circuit equipped with two one-way valves that directed the expired gas into a 100-L bag in a box, which was in turn connected to a Tissot spirometer. The inspired oxygen contained less than 0.00001% CO. At hourly intervals minute ventilation was measured, expired gas samples were collected and analyzed for CO, and venous blood was drawn and analyzed for [COHb]. The rate of CO excretion (VEco) was calculated from the minute ventilation and CO concen...

Since the late 19th century, carbon (CO) has been known to be present in of normal man and animals. The origin in blood, however, has not been entirely Although it might be assumed that all CO is absorbed from the environment, thors have thought that some, at least, endogenously. The difficulties in de whether blood CO arises endogenously oi been the lack of knowledge of the vari govern CO uptake and loss from the uncertainty of the degree of exogenc sure to CO, and the lack of accurate ar CO analytical methods.In 1894, Grehant (1) monoxide nous and endogenous origin of the gas. In rethe blood cent years, the endogenous formation of CO has of the gas been studied by Sjdstrand and his associates in explained. Sweden (6, 7). the blood These investigators, however, have not measmany au-ured the actual rate at which CO is formed. The is formed instrument 1 used in their experiments to analyzẽ termining CO actually measures the temperature increase r not have during its catalytic combustion. In our hands, it is ables that relatively nonspecific for CO, and it seemed posbody, the sible that some of their findings might have been )us expo-produced by the presence of gases other than CO. id specific Their conclusion that CO is produced in normal man (7) depended on the demonstration of )rmal dog higher CO concentrations in expired than in in-)mbustible spired air. This, however, could be possible in the >), Leoper absence of endogenous CO formation if an unbloed (5) steady state existed between blood CO hemogloin human bin (COHb) and inspired CO concentration; this an exoge-could have occurred if their subjects had been exposed to higher CO concentrations in the environment as long as several hours before the experiments. We have developed an analytical method that appears to be specific for CO and can detect the addition of 0.3 ml of CO to the total adult C 0 2 human CO store by the analysis of a 2-ml blood A B SO R B E R sample (8). We have overcome some of the other criticisms by measuring the increase in blood COHb during extended periods of rebreathing in a closed system. METHODS

This randomized trial demonstrates the utility of palliative SBRT for spinal metastases, which was associated with a quicker and improved pain response. Larger ongoing randomized studies will assist in further addressing these endpoints.

Pulmonary capillary blood flow (Qc) and apparent CO diffusing capacity (Dl) were calculated from the rates of disappearance of small alveolar concentrations of inspired acetylene and carbon monoxide during breath holding. Such measurements were performed simultaneously in four normal subjects at rest, during exercise and while performing Valsalva or Mueller maneuvers; they were also made at more than one alveolar oxygen tension so that true membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc) could be calculated by the method of Roughton and Forster. Dl, Dm and Vc were closely correlated with Qc (r = 0.92, 0.71 and 0.92, respectively), indicating that both volume and effective surface of the pulmonary capillary bed changed along with corresponding directional changes in blood flow. During transients after starting or after stopping exercise, changes in Dl lagged slightly behind the associated changes in Qc; both parameters tended to reach steady values, however, after about 1 minute of steady exercise. The average time spent by red cells in the pulmonary capillaries at rest was estimated to be 0.79 second, falling to about 0.5 second at levels of exercise at which volume flow through the capillary bed was approximately tripled. Submitted on September 18, 1959

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