some storage compound. The previous action of oxygen has, no doubt, contributed to the formation of any such compound; oras Pflüger expressed it-absorbed oxygen has helped to wind up the clock, discharged carbon dioxide is the sign of its running down. To this storage substance, which, however, is not a real and identified compound, but only a hypothetical idea, Hermann has given the name 'Inogen' (from is, ivós, force, or muscle), on account of the supposition that it is the force-producing material in muscular contraction. The extraction of muscle gas, which is exclusively carbon dioxide, under various conditions of experiment, furnishes data upon which conclusions are based. By raising the temperature to 40° or 50°, muscle is made rigid or 'rigored'; it becomes acid, and the primary discharge of gas is rapidly completed; the addition of phosphoric acid now liberates a further small quantity of carbon dioxide. The carbon dioxide removable by vacuum is termed 'free'; that removable by acid is termed 'fixed'; the total volume of carbon dioxide (free and fixed) thus obtainable from muscle is 1 to 15 vols. per 100. If muscle is suddenly heated to 70°, it is fixed without passing through the stage of true rigor; it is said not to acidify, and no carbon dioxide is discharged; what gas happens to be in the muscle at the time is obtainable from it by vacuum and by acid, but the hypothetical storage compound inogen is fixed' and rendered incapable of further change. This process, technically known as 'scalding,' renders possible certain comparisons. Thus, comparing the amounts of gas obtainable from scalded fresh muscle and from scalded tetanised muscle, much more carbon dioxide is obtainable from the latter than from the former. Comparing scalded fresh muscle with rigored muscle, more carbon dioxide is obtainable from the latter than from the former. Rigored yields more carbon dioxide than tetanised muscle. Finally, by comparing the amounts obtainable (a) from fresh rigored muscle, (b) from muscle which was first tetanised, then rigored, Hermann found that the rigor gas was less in (b) than in (a), and that the sum of rigor and of tetanus gases in (b) was about equal to the rigor gas obtained from (a). The conclusion drawn from these observations is that one and the same substance, 'inogen,' suffers dissociation and yields carbon dioxide in heat-rigor and in muscular contraction. Fresh muscle minced and boiled for two or three hours yields as much as 100 vols. carbon dioxide per 100 vols. muscle. Muscle which has been tetanised or heat-rigored and allowed to exhale the CO2 thus produced, subsequently yields about 30 vols. per 100 on boiling. The substance from which carbon dioxide is thus produced is presumably Hermann's inogen, and we are led to suppose that, besides its physiological dissociation in muscular contraction, it dissociates slowly post mortem (deathrigor), rapidly at 40° (heat-rigor), is fixed at 70° (scalding), again dissociates at 100° (boiling). In contraction, after death, and at 40°, muscle yields CO, and becomes acid; at 70°, although it becomes rigid, it does not yield CO, nor become acid; at 100° it yields CO, and becomes acid. 2 The gaseous exchanges taking place between muscle and blood have been more particularly studied in France by Claude Bernard, in Germany by Ludwig and by Pflüger. Bernard observed the fundamental fact that venous blood coming from muscles is darker during their contraction than during their quiescence. The difference is obviously due to the greater deoxygenating effect of active than of resting muscle, and if we take into account that the amount of blood that passes through the muscles is greater during contraction than during rest, in consequence of the vascular dilatation which accompanies contraction, we must recognise that the absolute amount of carbon dioxide produced by muscle is much greater during contraction than during repose. Bernard's estimates do not, however, supply any exact numerical expression for this difference. Ludwig and his pupils Schmidt and Sczelkow, attempted to fill this gap by the gas-analysis of blood made to circulate artificially through excised muscles, as well as of blood coming from living muscle in situ. They confirmed the fundamental fact that active muscle consumes more oxygen and produces more carbon dioxide than resting muscle, but the conditions of experiment were too far removed from the normal for it to be allowable to admit as normal the numerical data obtained. Later experiments in the same laboratory by v. Frey have shown that the consumption of O, under such conditions is not more thanth to th the normal, whereas the production of CO, and of lactic acid was comparatively large. Pflüger, in conjunction with his pupils Stintzing and Finkler, criticised and rejected Ludwig's conclusions, in particular the statement that the amount of oxygen in the blood and the amount of the latter passing through the muscle, determine the energy of CO, production. They uphold by very convincing arguments the precisely opposite doctrine, to wit, that the activity of muscle determines the oxygen consump tion, not that the oxygen-supply determines muscular activity. The possible connection between lactic acid and CO, in rigor and in contraction will be considered under 'Muscle.' 2 To sum up :-The activity of muscle-respiration is determined by the activity of muscle, and not vice versâ. The consumption of oxygen is determined by the oxygen requirements of tissue, not by the amount of oxygen available. The exhalation of carbon dioxide is the most reliable indicator of muscle-respiration. By integration of oxygen a force-yielding storage substance is formed. By disintegration of this substance carbon dioxide is liberated, in company with heat, work, acid, and an alteration of electrical potential. • Pressure' or 'tension' of gas. 'Partial pressure.'-The pressure of the atmosphere is equivalent to that of a column of mercury about 75 centimeters high. Atmospheric air is a mechanical mixture of oxygen and nitrogen-in round numbers, 1 part oxygen to 4 parts nitrogen. The pressures of oxygen and of nitrogen in the mixture are proportionate with their respective volumes, i.e. the total pressure (=15 cm. Hg) is the partial pressure of oxygen, the total pressure (=60 cm. Hg) is the partial pressure of nitrogen. More generally expressed, the total pressure or tension of a mixture of gases is equal to the sum of the partial pressures or tensions of the component gases. In the case of air the total pressure (75 cm. Hg) is equal to the partial pressure of oxygen (15 cm. Hg) plus the partial pressure of nitrogen (60 cm. Hg). Thus, if the percentage of gas in a mixture is known, the total pressure being also known, the partial pressure of the gas is obtained by a simple calculation. The percentage of oxygen in air being 20, the pressure of air being 75 cm. Hg, the partial pressure of oxygen is cm. Hg=15 cm. Hg. 20 x 75 100 The same laws apply to simple solutions of gases in liquids when chemical forces do not intervene, but in the case of blood, in which the gases are held in loose combination, their partial pressures cannot be calculated from the percentage, and must be ascertained by direct observation. For example, in blood containing 12 vols. O, per 100, the oxygen, in the absence of chemical force, would have a tension or partial pressure cm. Hg= 9 cm. Hg.; whereas by direct experiment its 12 × 75 100 40 x 75 100 tension is found to be much lower, i.e. about 2 cm. Hg. Similarly, in blood containing 40 vols. CO, per 100, the CO, if simply dissolved would have a tension = cm. Hg=30 cm. Hg; whereas by direct experiment its tension is found to be much lower, i.e. about 4 cm. Hg. The explanation in both cases is that the gases are held in loose chemical combination. Thus the blood-gases do not conform to the Henry-Dalton law of pressure, according to which the volume of gas dissolved in a fluid varies directly as the pressure; if pressure is gradually lowered in the blood-pump, the gases are not evolved pari passu, their dissociation from the blood at temperatures between 37° and 17° C. does not take place in abundance until the pressure is reduced to between and of its normal value. The tension of CO, in the blood is ascertained by the aërotonometer. This in principle is an apparatus in which blood is brought into close relation with two gaseous mixtures, in one of which the CO, tension is above, while in the other it is below, the anticipated CO, tension of the blood. When blood is allowed to dribble through the apparatus it takes CO, from the first mixture, and yields CO, to the second, and from these data a fairly accurate estimate of CO, tension in the blood is derived. For example, if in the two parts of the tonometer the original CO, tension were equivalent to 3 and to 6 cm. Hg respectively, and if by the action of blood on the two mixtures these values were increased to 4 and diminished to 5 cm. respectively, the tension of CO, in the blood would be estimated at 4.5 cm. Hg. The CO, tension of alveolar air is obtained by the pulmonary catheter; this is essentially a double tube, the outer part of which can be dilated so as to block a bronchus, while the inner channel remains in communication with the air beyond the blocked point. The bronchus being blocked, a portion of the lung is cut off from ventilation, and the tension of the contained gas soon equalises the maximum tension of gas in the pulmonary capillaries. The CO2 tension in the alveolar air Wolffberg thus found to be equal to the CO, tension in venous blood, and not much greater that that of expired air. 2 2 An idea of the relative magnitudes of the O, and CO, tensions in various situations may be gathered from the subjoined table, principally composed of data supplied by the observations of Wolffberg and of Strassburg on the dog. With reference to these numbers, it is to be remarked that they denote magnitudes which are presumably lower than normally exist in the human subject, seeing that the CO2 of expired air averages 3 per cent. (=2.25 cm. tension) on the dog, and 4 per cent. (=3 cm. tension) on man; for blood we have taken in round numbers the tension of 3 cm. Hg as that of CO, and of O2, but as might be expected arterial and venous bloods differ in this respect-representative values are 3 cm. O, tension, 2 cm. CO, tension in arterial blood, 2 cm. O, tension and 4 cm. CO2 tension in venous blood; as regards alveolar air, the value of the CO, tension given is that of blocked alveoli; the value of O, tension is an approximate value of what, judging from the partial pressure of O, in the pleural cavity (57), presumably obtains in the unblocked alveoli; in blocked alveoli the O, tension falls to that of the pulmonary blood, viz. 3 cm.; the difference in the CO2 tension of alveolar and expired air is not so great as might have been expected-in other words, the diffusion of CO, is extremely rapid. As regards lymph, it is to be observed that the CO, tension actually observed is very variable, sometimes exceeding, sometimes falling short of the CO2 tension in venous blood, and that the O, tension is not always at zero; this is attributable to the fact that under the conditions of experiment more or less gas diffuses between lymph and the arterial blood of neighbouring vessels. The passage of oxygen from the atmosphere to the blood and to the tissues, as well as the passage of carbon dioxide from the tissues to the blood and to the atmosphere, can thus be accounted for on purely physical grounds, the incoming current of O, and the outgoing current of CO, being regarded as ordinary diffusioncurrents. The diffusion of oxygen is directed from atmospheric to alveolar air, from alveolar air to blood, from blood to tissue. The diffusion of carbon dioxide is directed from tissue to blood, from blood to alveolar air, from alveolar to atmospheric air. The concurrence of forces other than diffusion has been invoked to account for the discharge of CO,. It has been shown. |