THE ELIMINATION OF CARBON MONOXIDE FROM THE HUMAN BODY WITH REFERENCE TO THE POSSIBLE CONVERSION OF CO TO CO 2

232

131

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

Section: Discussionmentioning

confidence: 56%

Endogenous Carbon Monoxide Production in Man*

Coburn¹,

Blakemore²,

Forster³

1963

232

131

“…An explanation of this apparent discrepancy be-' tween the efficiency of CO production from heme and bile pigment production from heme may lie in the fact that CO is probably produced in the initial steps of hemoglobin catabolism (21,22) and is metabolically inert (23), whereas the remaining tetrapyrrole moiety is subject to a variety of reactions in the process of production of the bile pigments. On the basis of the present study it seems very probable that CO produced as an end product of hemoglobin catabolism forms a large percentage of the normal CO production.…”

Section: Discussionmentioning

confidence: 99%

Effect of Erythrocyte Destruction on Carbon Monoxide Production in Man*

Coburn¹,

Williams²,

Forster³

1964

107

Recent studies performed in our laboratory (1) have confirmed the finding of Sjdstrand (2, 3) that carbon monoxide is produced in normal man. In 10 normal subjects the average rate of production of carbon monoxide was found to be 0.42 (SE of mean + 0.02) ml per hour. The present study is an attempt to clarify the processes that result in the production of this gas in the body.A number of studies have been performed that suggest that CO may be an in vivo catabolic byproduct of hemoglobin. Sj6strand and associates have demonstrated that the blood carboxyhemoglobin concentration [COHb] becomes elevated in man after intramuscular or intravenous injection of blood or hemoglobin (3) and intravenous injection of damaged erythrocytes or nicotinic acid (4). Sj6strand (3) and later Engstedt (5) and Oski and Altman (6) noted that the blood [COHb] level is elevated in patients with hemolysis. Chemical studies by Sj6strand (7,8) and Ludwig, Blakemore, and Drabkin (9) have demonstrated that treatment of hemoglobin (7,8) and pyridine hemochromogen (9) with hydrogen peroxide and ascorbic acid results in CO formation. In the latter study the bridge and adjacent carbon atoms of heme were labeled with C14, and the CO formed was found to be radioactive, indicating that CO probably arose from a methene bridge carbon atom.* Submitted for publication November 18, 1963; ac- (10) have shown that coupled oxidation of heme is a different reaction than occurs physiologically during heme catabolism in that the porphyrin ring is apparently randomly opened at any of the four methene bridge carbon atoms rather than at the alpha position as occurs in vivo (11). Because of these uncertainties, our method for estimating in vivo CO production quantitatively was applied to this problem. This paper contains data on measurements of the rate of endogenous carbon monoxide production following the intravenous injection of damaged erythrocytes in man. MethodsEndogenous CO production was measured by the "rebreathing method" described in greater detail elsewhere (1). The principle of this method is that CO excretion from the body, which occurs via the lungs, is inhibited by having the subject rebreathe in a closed system. Endogenous CO production is then calculated from the rate of increase in venous blood [COHb] during rebreathing and the effective blood volume, both of which are measured in every study. With this technique the production of CO per hour, calculated from two blood samples, drawn at the beginning and end of the period, could be estimated in each hour with an error of less than ± 0.2 ml. Greater precision was ob-1098

“…The first consists of production and excretion of endogenous CO. CO, which is apparently produced completely or mainly in the liver and spleen as a catabolic by-product of heme, diffuses into the blood and red blood cells, becomes bound to hemoglobin, and is diluted in the body CO stores. CO is apparently not metabolized in significant amounts by the body (19). It is excreted from the body via the lungs.…”

Section: Methodsmentioning

confidence: 99%

Considerations of the physiological variables that determine the blood carboxyhemoglobin concentration in man.

Coburn¹,

Forster²,

Kane³

1965

409

207

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...