A comprehensive analysis of pulmonary fuinction must include measurements of pulmonary ventilation, diffusion, and circulation. An accurate measurement of alveolar ventilation, independent of diffusion and circulation, is desirable. To date, no method has been wholly satisfactory (3). One approach has been by study of the time course of equilibration of alveolar gas with a "foreign" inspired gas, such as H2 (4) Most simply, the lungs could be represented by a bellows which is uniformly ventilated, i.e., inspired gas is distributed evenly to and mixed instantly with all the gas previously present in the bellows. For simplicity, it will be assumed for the moment that inspired gas contains no N,, and that there is no transfer of N2 from blood and tissue.
In 1915, M. Krogh reported the use of carbon monoxide in an ingenious technique for the measurement of the pulmonary diffusing capacity in man (1). In her method a maximal inspiration of a gas mixture containing CO was made from residual volume and followed immediately by an expiration of at least one liter of gas. The breath was held at the remaining volume for 6 to 10 seconds, and then a maximal expiration was made. The terminal volumes of the two expirations were considered to be alveolar gas and were analyzed for CO concentration. M. Krogh assumed the CO concentration decayed exponentially and derived the following equation to describe this decay.FA= FAO exp (-DPbt) (1) FA is alveolar concentration of CO (dry) at time t (Krogh's final sample); FAO is the alveolar concentration (dry) at time zero (Krogh's initial sample); "exp" is e, the base of the natural logarithms, raised to the power contained in the brackets following; D is the pulmonary diffusing capacity for CO in ml. STPD/mm. Hg X sec.; VA is the total alveolar gas volume in ml. STPD during the period of breathholding, obtained from a spirometer tracing and from measurement of functional residual capacity; t is time in seconds between the delivery of the two gas samples; and Pb is the total barometric pressure minus 47 mm. Hg. The In order to derive Equation 1, Krogh had to make the following major assumptions: (a) that the CO concentration in the first sample was representative of all alveolar gas; and (b) that the CO tension in the pulmonary capillary5 plasma (P0) was negligible. Although her technique involves delivering two expired alveolar samples, these are actually parts of the same expiration, being separated by the breathholding period. It is now known that these two alveolar samples would not have the same initial CO concentration (2). Furthermore, Roughton has indicated that P0 may not be negligible (3), casting doubt on the validity of the second assumption. Therefore, it was decided to reinvestigate the disappearance of CO from the human lung during breathholding following a single inspiration of a gas mixture containing CO. Recently developed physical methods of gas analysis, in particular mass spectrometry and infrared absorption techniques, were used throughout.At first Krogh's experiments were repeated as she described them (1) and values for the pulmonary diffusing capacity were obtained which agreed with those she reported. However, the calculated value of the pulmonary diffusing capacity varied with the length of time the breath was held, which is incompatible with Equation 1. In order to investigate this phenomenon further, the experimental procedure was modified. Only one expired sample was obtained, and the initial CO concentration (FAO) was computed from the dilution of an insoluble gas (He) contained in the inspired mixture. This obviated the necessity of comparing CO concentration in two different alveolar gas samples, and thereby eliminated the need for Krogh's first premise above. The breath was held for different length...
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