The physiological significance of the alveolar carbon dioxide has been emphasized in practically all studies of the respiration in recent years. The delicacy of the regulation of the mechanism for respiration and the important r61e played by alveolar carbon dioxide are becoming increasingly evident. Although in the earlier stages of the investigation sufficient data were secured in the respiratory studies to compute the alveolar carbon dioxide by assuming a constant dead space, we deemed it important to make direct studies of this factor. Unfortunately these studies were not begun until about the middle of November. Thereafter direct alveolar carbon-dioxide determinations were carried out by the method outlined on page 79 in connection with each experiment with the respiratory-valve apparatus. The technique used gives results1 comparable to those obtained by the Plesch-Higgins1 method, and consequently the values approach the carbon-dioxide tension of the venous blood rather than that of the arterial blood. These values are recorded in column g of table 111. In almost every instance they represent the average results of two well-agreeing determinations obtained immediately after the respiratory-exchange experiments, the subjects being always under uniform conditions. While the agreement of these values with a large number of the subjects is perhaps all that could be expected, certain instances, such as the variation with Mon of 43.2 to 50.1 mm., is rather wider than one would normally expect, likewise that with Gul from 41.6 to 48.5 mm., with Pea from 39.9 to 49.9 mm., with Pec from 40.2 to 47.2 mm., with Spe from 35.1 to 44.8 mm., and with Vea from 31.9 to 49.4 mm. On the whole the values lie considerably above 43 mm., which is about that ordinarily found with normal individuals. It seems important, also, to find if the variations from day to day were inherent in the method or were actually existing with all subjects. Fortunately for this purpose we have comparable values for comparison which were calculated from the respiratory exchange as determined by the respiratory-valve apparatus.

1Roth. Boston Med. and Surg. Journ.. 1918. 179, p. 130. 2Higgina, Carnegie Inst. Waah. Pub. 203, 1915. p. 171.

This computation was carried out in the usual way by using the ventilation of the lungs and the carbon-dioxide production according to the following formula:

Alveolar carbon dioxide (per cent) =Carbon dioxide excreted per minute/ Total ventilation - (Respiration rate X140 c.c. dead space).

Per cent C02 X barometric pressure - 47 mm. = tension in millimeters.

This method of computing the alveolar carbon dioxide involved the use of a constant dead space in the respiratory passages of 140 c. c, in accordance with the method used by Loewy and Zuntz.1

The irregularities noted from day to day with Pea seem to be verified in large part by the computed values, although certain exceptions appear contrary to this. Thus the low value of 39.9 mm. found by the direct method on November 16 is not accompanied by a low value computed by the indirect method. It should be borne in mind that the computation method assumes a constant dead space for all the subjects. This might introduce an error in comparisons of values for different subjects, but it is hardly probable that the dead space would change so profoundly from day to day as to effect a real variation in the calculated alveolar carbon dioxide. Therefore the comparison of the variations in the two sets of values is based on sound principles. Although we had the cooperation of the subjects and the long period of observation made them thoroughly familiar with the technique, the fact that somewhat more regular values for the alveolar carbon-dioxide tension are found by the computation method than those secured by direct determination should not be lost sight of, and this leads one to believe that the calculated values in the long run probably have a higher degree of accuracy and their variations from day to day are more to be relied upon than are those directly determined. Consequently we may compare, with an even greater degree of confidence, the relationship between the calculated values for the alveolar carbon dioxide at the beginning and end of the long period of undernutrition to see what effect the undernutrition had upon the alveolar carbon dioxide.

1 Loewy and Zuntz, Berl. klin. Wochenschr., 1916, S3, p. 828.

Comparing the one or at most two observations before the diet with the average of the last 3 days of the low diet, we find that with Bro, Can, Gar, and Pea there was practically no change, with Gul a slight tendency for an increase at the end, and with Mon and Moy a slight decrease. With Pec there was a distinct falling off in the alveolar carbon dioxide, with Tom no material change, and with Vea possibly a slight increase. From a comparison made on this basis, it is difficult to note any particular alteration in the alveolar carbon dioxide due to the altered dietetic conditions, there being no decided tendency, on the average, for the alveolar carbon-dioxide tension to change even after extensive dietetic alterations.

Alveolar Carbon Dioxide And Irritability Of Respiratory Center

As Loewy and Zuntz1 point out, unusual significance attaches to the alveolar carbon dioxide since the reaction of the respiratory center to the alveolar carbon dioxide may be taken more or less as an indication of the irritability of the organism. It has been their custom in many of their respiration experiments to compute the relationship between the alveolar carbon dioxide and total ventilation of the lungs, i. e., to express in cubic centimeters per minute the amount of ventilation, not reduced, per millimeter of carbon-dioxide tension in the lungs, and such determinations were made in their experiment on war diet.

Similar computations for our experiment seemed desirable. These have been made on two bases: first, from the alveolar carbon dioxide as actually determined, and second, that found by calculation. The ventilation per minute was obtained by dividing the observed ventilation (see column a) by the tension of carbon dioxide, either determined or computed. The results are recorded in cubic centimeters per minute per millimeter of carbon-dioxide tension in columns h and i, the first being computed from the calculated carbon-dioxide tension and the second from the direct determinations. Bearing in mind the fact* that no pronounced tendency was found for the alveolar carbon dioxide to change during the experiment and that in general there was a distinct tendency for the total ventilation of the lungs to become lower as the experiment progressed, one is prepared to find that the ventilation per minute per millimeter of carbon-dioxide tension has a definite tendency to decrease as time goes on.

1 Lovwy and Zunts. Berl. klin. Wochenachr., 1916, 53, p. 825.

Examining first the values drawn from the calculated carbon-dioxide tension (column h), we find with Bro a decided fall of approximately 20 c.c. per minute, with Can, Gar, and Gul a decrease, while with subject Mon there was a tendency for this value to remain constant. With Moy there was an increase from 104 c.c. to an average not far from 116 c.c. With Pea, Tom, and Vea, on the contrary, there was the usual fall, and with Pec practically constant values. In general, the values based upon the calculated alveolar carbon dioxide show a clear tendency to a somewhat less ventilation of the lungs per millimeter of carbon-dioxide tension.

In comparing the calculations based upon the direct determinations of alveolar carbon dioxide, which, unfortunately, were not obtained until after the middle of November, we find that no pronounced or regular change in the ventilation per millimeter is apparent with Bro, Can, Kon, Gar, Gul, Mon, Pec, or Tom. (See column i.) On the other hand, Moy's values show a tendency to fall, although high values are found in the early part of January. The values for Pea tend to decrease, as do those obtained in one month's observations with Spe. The general picture with Vea is similar, although high values are again found in the early part of January and the results with him on the whole are irregular.

One must conclude, therefore, that the tendency shown by both sets of figures is, in certain cases, for the ventilation per minute per millimeter of alveolar carbon-dioxide tension to be somewhat lower at the end of the period of reduced diet than at the beginning. In other words, the respiratory center is somewhat less sensitive at the end than before the reduction in diet began, this decrease in sensitivity being due to the low diet. This is in contrast to the results reported by Loewy and Zuntz.1 No change was found with Loewy, and although variations with Zuntz had been found from time to time during a series of years, as a matter of fact the ventilation per millimeter of alveolar carbon dioxide in the experiment with the war diet was exactly that found with him 28 years before. Their general conclusion is that the low diet did not increase the sensitivity of the respiratory center.

Dr. T. M. Carpenter calls our attention to the fact that with a decrease in respiration rate as shown in a previous section there would be a decrease in the total ventilation, because the personal dead space of the subject would not have to be swept out so many times with a slower respiration rate. This, together with the fact that there was less carbon dioxide to be eliminated, naturally resulted in a lower total ventilation, so that with a fairly constant level of carbon-dioxide tension there would result mathematically a lower volume of expired air per millimeter of carbon-dioxide tension. To say that this means a change in irritability of the respiratory center would seem to imply that if there is a change in any of the factors of respiration, such as respiration rate, dead space, carbon-dioxide elimination, and total ventilation, the irritability would be also changed. So that when we say that the irritability of the respiratory center is decreased with these subjects, it is only in the sense that Loewy and Zuntz use the term.

1 Loewy and Zuntz, Berl. klin. Wochenschr., 1016, 53, p. 825.

The general conclusions from the study of the mechanics of respiration and particularly the alveolar air for the subjects in our research are that the low diet produces a distinctly lower respiratory activity, and although the alveolar carbon dioxide remains essentially constant, there is a definite tendency toward a lessened work of ventilation, with a decreased sensitivity of the respiratory center. The correlation of this finding with the total metabolism must be noted in subsequent discussion. The general lowering of the metabolism shown calls for a lower ventilation of the lungs for the removal of carbon dioxide and hence the work of ventilation is less.

Subsidiary evidence regarding the reasonable constancy in the alveolar carbon dioxide is supplied by the fact that the alveolar carbon dioxide with Pea was directly determined before a cross-country run on November 28 and found to be 48.4 mm.; immediately after the cross-country run, which was 6$ miles (10.9 km.), it was found to be 42.9 mm. The respiration rate under these conditions was, as found from kymograph records, 18.3 respirations per minute prior to the run and 23.3 respirations subsequent to the run, although it was impossible to adjust the apparatus and get a record until some little time had elapsed after the completion of the run.