From the standpoint of the conditional method of investigation it is at once apparent that specific energy, as well as specific irritability, must be solely determined by the specific conditions existing in the particular system. It follows from this that every alteration in the conditions of the system, that is, every change of its state, likewise entails a corresponding alteration of its specific energy and its specific irritability. It is, therefore, self-evident that the alteration of the state, which is undergone by the living system in the process of excitation, brings about an alteration of its specific irritability. Likewise as the original state of the system is restored by the metabolic self-regulation after the course of an excitation, the specific irritability of the system must be reestablished. The specific irritability is, therefore, a property of the living system, which, like the metabolic equilibrium, undergoes restitution by the process of self-regulation after variation produced by a stimulus of any kind. It is scarcely necessary to repeat each time that this is only applicable within the physiological variations and for a limited period, during which the alterations in development need not be considered.
These alterations of the specific irritability following an excitation and their compensation through the metabolic self-regulation will now claim our attention.
That the specific irritability of a living system undergoes a diminution as the result of a stimulus of long duration has been long known through the study of fatigue. This is especially so with frequently recurring excitating stimuli. It is only within the last decade, however, that the observation has been made in a few instances that a single momentary excitation is likewise followed by such a reduction of the specific irritability. But that this is a fact of general physiological fundamental importance for the whole field of response to stimulation in the living substance has only been recognized within the last few years.
Fig. 29.
Eight series of heart contractions. The dotted lines e show the moment of an artificial stimulus. The artificial stimulus is ineffective if it is applied before the height of a systole. The artificial stimulus becomes the more effective in producing an extra systole, followed by a compensatory pause, the later it is applied after the height of the systolic contraction. (After Marey.)
In 1876 Marey[119] found that the irritability of the heart in response to artificial stimulation was greatly reduced during the systole, and that recovery took place during the following diastole. (Figure [29].) This fact was already apparent from the observations made by Bowditch[120] and Kronecker,[121] that by stimulation of the isolated frog’s heart with single induction shocks, an artificial systole can only be produced with certainty when the stimuli succeed each other at certain intervals, which must be the longer as the strength of the stimulation is weaker. Marey calls this period of reduced irritability “phase réfractaire” of the heart. The refractory period of the heart has been made the subject of a great number of investigations, especially by Engelmann and his pupils. It was Engelmann[122] especially who determined more exactly the duration of the course of the refractory period. He found, namely, that irritability disappears immediately before each systole and reappears shortly before the beginning of the diastole, and again reaches its original height at the end of the diastole. For a long time, however, this refractory period was looked upon as a special peculiarity of the heart. It was not until Broca and Richet,[123] twenty years after Marey’s investigations, discovered an analogous refractory period for the motor centers of the cerebral cortex of the dog. They first made this observation on a dog affected with chorea, in which the choreic movements rhythmically occurred in intervals of one second. They found that after each movement electrical stimulation of the cortex remained without result for about .5 seconds. During the next .25 seconds stimulation was followed by a weak response and it was not until the last .25 seconds before the next movement that a strong effect was produced. They also found in the normal dog a refractory period after every artificial stimulation equal to .1 second, so that the number of contractions brought about by rhythmical electrical stimulation were only ten per second. Following this, numerous other investigations of the refractory period have been made on the central nervous system. Zwaardemaker[124] and Lans have observed a refractory period in the eyelid reflex of the human being which, on stimulation of the optic nerve, amounts to about .5–1 second; on the stimulation of the trigeminus produced by blowing on the cornea on the other hand, it is somewhat shorter, less than .25 seconds. Zwaardemaker[125] also was able to demonstrate an analogous refractory period for the swallowing reflex of the cat. Further a refractory period was found and closely analyzed by Verworn[126] for the reflexes in the spinal cord of the strychninized frog. Dodge[127] found a refractory period in the knee jerk reflex of man. Gotch and Burch[128] showed, by two induction shocks following each other in quick succession, a refractory period of the nerve, which is characterized by its extremely brief duration. They found, depending upon the temperature, a period of nonirritability of .001–.008 seconds after every stimulus. The investigations of Miss Buchanan[129] lead us to conclude that there is a refractory period for the cross striated skeletal muscle. Miss Buchanan stimulated the muscle at times through the nerve, at other times directly after elimination of the nervous element, with very frequent electrical stimuli (about 1000 in the second) and found by means of the capillary electrometer a rhythmical reaction of the muscle of about 50–100 excitation shocks per second. Likewise the Ritter tetanus produced by the breaking of an increasing current proved to be a rhythmical reaction of an analogous nature. In a more direct manner Keith Lucas[130] has determined the refractory stage for the musculus sartorius of the frog. He allowed two induction shocks to act successively on the muscle at intervals of varied duration and then registered the action currents by means of the capillary electrometer. He then found that the second stimulus was ineffective for about .005 seconds after the application of the first stimulus. If the second stimulus follows somewhat later, it produces a contraction which is weaker and has a longer latent period the nearer the second stimulus approaches the first in point of time. (Figure [30].) Massart[131] and Jennings[132] likewise observed the existence of a refractory period for the myoids of unicellular organisms brought about by mechanical stimuli. Massart attributes this cessation of reaction to stimuli following each other at certain intervals, to fatigue, an explanation which has been disputed by Jennings as the result of his investigations made on Stentor and Vorticella. Jennings looks upon the behavior of the infusoria rather as an “adaptation” to the stimulus. Pütter was the first to see in this the existence of a refractory period. His experiments on Spirostomun ambiguum in 1900 showed a refractory period in the reaction to rhythmical mechanical stimuli. I wish to state, however, that these observations of Pütter have not as yet been published. Thus the existence of a refractory period has even today been proved for a whole series of very different kinds of substances.
Fig. 30.