Because of the difficulty described above in applying the Fick principle to man, other avenues of approach to the problem were sought. Another type of method, based on a determination of the rate of absorption through the lungs of some foreign gas, has been investigated. The idea underlying this type of method is quite simple in principle. If we take some physiologically inert foreign gas which will pass into the blood in simple physical solution, determine its solubility in blood, and then find out how much of this gas is absorbed by the blood passing through the lungs from the right to the left side of the heart in a given short interval of time, we can obviously calculate how much blood must have passed through the lungs in that time to dissolve the observed amount of gas. This amount of blood flowing through the lungs represents the output of either side of the heart. In practice, however, this method bristles with difficulties and questions as to its accuracy. Thus, we must be sure that complete equilibrium is attained between the gas mixture in the lungs and the flowing blood, that the time allowed for the experiment is sufficiently short to prevent any return of blood containing the foreign gas; that the heart output is not changed by the procedure used, and so forth. Only quite recently have methods based upon this general principle been put upon a firm basis as to their accuracy.

Since the above type of method has many advantages as to accuracy and simplicity over that based upon the Fick principle, we may describe briefly just how a determination of the cardiac output is carried out with it. Of the foreign gases used - namely, nitrous oxide, ethylene, and acetylene the latter has proven the most satisfactory. The subject, after a period of rest or exposure to some special condition under which the determination is to be made, has his oxygen consumption determined by one of the usual methods. He then rebreathes from a rubber bag a mixture of acetylene and air for a period sufficiently long to bring about mixture in the lung-bag system (fifteen to eighteen seconds) and a sample of gas is taken from the system. After five seconds more, another sample is taken. An analysis of these two samples, the barometric pressure, and the oxygen consumption give all the data necessary for calculating the output of the right side of the heart, and hence also of the left side. The technical details cannot be discussed here.

What results have been obtained by the use of these cardiac output methods on man? In the first place, it has been found that a man in the basal condition (eighteen hours after food and at complete rest) has a cardiac output of 2.2 liters for each square meter of body surface. This means that, depending on the size of the individual, his heart pumps each minute from three to six liters or from nearly a gallon to a gallon and a half of blood. Moreover, at each beat of the heart a little over two ounces of blood is discharged. The cardiac output of any individual under standard conditions is a very nearly constant quantity, varying only slightly from day to day. Many influences, however, modify the amount of blood being circulated around the body. Thus, the ingestion of food increases the cardiac output, a large meal having a greater and more lasting effect than a small one. The emotional state of the subject is also of importance, for emotional disturbances may raise the value above the basal normal. In muscular exercise, the output of the heart may be enormously increased, and, of course, this is necessary to supply the active muscles with oxygen.

Many other quantitative data of great interest have also been obtained by the use of these methods for determining the output of the human heart, but there is still need for more information concerning variations of the normal under different physiological conditions, not to mention the application of the methods in disease. One of the most surprising conclusions, however, from the results already obtained is that the heart rate is no indication of the amount of blood which the organ is discharging per minute. Thus, a fast pulse may be accompanied by a decreased, and a slow pulse by an increased, output per minute.

Concerning the regulation of the cardiac output of the human subject, much remains to be determined. We know with certainty that ingestion of food, changes of external temperature, psychic disturbances, lowered oxygen tension in the inspired air, and muscular exercise all change the cardiac output, but we are at present far from understanding the mechanism by which these changes are brought about. It is, of course, obvious that the output of the heart cannot exceed its input; hence, where the cardiac output is increased, the input must be increased. But whether this increased venous return to the heart is brought about primarily by changes in the cardiac mechanism, by alterations in the blood vessels, or by both, cannot be stated with certainty at present.

The above brief description of how the problem of the cardiac output of man has been attacked presents an instance of what may be called quantitative descriptive physiology; as yet the explanatory or theoretical side has just begun. Let us now take another example from the different field where the trend of recent work has been more on the explanatory than on the descriptive side. We say that we can explain a mechanism or a process in the animal organism when we can express it in terms of known physical or chemical laws. In many cases, this cannot be done, and we can then only express the process in terms of what may be called "physiological laws." A good example of these two types of explanation will be found in recent work on the physiology of kidney excretion.