The liability to fatigue of the respiratory center is a subject which needs to be studied. Davies, Haldane, and Priestley (1) were the first to investigate the manner in which breathing adapts itself to increased resistance, and the point at which the adaptation begins to fail. They showed that the normal response in man to respiratory resistance in both phases of respiration is slow and deep breathing. When the resistance is excessive respirations become progressively shallower and more frequent and the subjects then become cyanotic. Haldane and his coworkers believe that this is due to fatigue of the respiratory center. They believe anoxemia hastens greatly the onset of fatigue and the ease with which it is produced. They conclude that the mechanism involved in the immediate response is the HeringBreuer reflex, pointing out that as a result of resistance, the time required for inflation or deflation of the lungs to reach the point at which the Hering-Breuer stimulus becomes effective is prolonged, that CO~ accumulates in the meantime, and that the next respiration is deep and vigorous. The more or less sudden onset of rapid, shallow breathing Haldane interprets as evidence of fatigue of the respiratory center, with a resulting predominance of the peripheral stimuli over the central impulses normally governing breathing.A study of these effects in animals was undertaken by us with several points in mind. We hoped for additional information as to the nature and origin of rapid and shallow breathing, which we have previously considered in both clinical and experimental studies (2-5). It seemed highly desirable to learn something about the liability to fatigue of so vital a structure as the respiratory center. Transferring the problem

1. Oxygen in concentrations of over 70 per cent of an atmosphere is poisonous to dogs, rabbits, guinea pigs and mice. 2. The poisonous effects manifest themselves in drowsiness, anorexia, loss of weight, increasing dyspnea, cyanosis and death from oxygen want. 3. The cause of oxygen want is a destructive lesion of the lungs. 4. The lesion may be characterized grossly as an hemorrhagic edema. Microscopically there is to be seen in varying degrees of intensity (a) capillary engorgement with hemorrhage, (b) the presence of interstitial and intraalveolar serum, (c) hypertrophy and desquamation of alveolar cells, (d) interstitial and alveolar infiltration of mononuclear cells. 5. The type of tissue reaction is not characteristic of an infectious process and no organisms have been recovered at autopsy from the heart's blood or from lung puncture. 6. The poisonous effects of inhalations of oxygen-rich mixtures do not appear to be related to impurities in the oxygen, nor are they related to faulty ventilation, excessive moisture or increased carbon dioxide in the atmosphere of the chambers in which the experimental animals were confined.

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1. Cutting one vagus nerve, while recording the pulmonary ventilation of each lung separately, has no unique effect on the ventilation of the denervated lung. Both lungs respond to unilateral vagotomy by an equivalent slowing and deepening of respiratory movement. 2. When the bronchus to one lung is blocked the first effect is a slowing and deepening of the respiratory movements recorded by the opposite lung. As oxygen want develops these movements become rapid and shallow. 3. With a combination of these two conditions, i.e., when the bronchus to one lung is blocked and its vagus nerve is severed, the pulmonary ventilation recorded by the opposite lung exhibits the same changes as may result from unilateral vagotomy alone, unaccompanied by occlusion of the bronchus. 4. From these facts it may be concluded that the slowing and deepening of breathing which follows unilateral vagotomy does not depend for its occurrence upon the passage of air in and out of the bronchus of the lung whose vagus nerve has been sectioned. 5. The slowing of respirations after occlusion of the bronchus to one lung and section of the corresponding vagus nerve still occurs even though the phrenic nerve on the same side has been divided. This indicates that the slowing of respirations following unilateral vagotomy does not depend on the movements of the diaphragm on the side of vagal section. 6. When the pulmonary artery to one lung has been ligated and the vagus nerve on the same side cut, the response of the other lung is the same as has been described, namely, its respiratory movements become slower and deeper. This is taken as evidence that the results of unilateral vagotomy are not dependent upon an intact pulmonary circulation. 7. The general conclusions from these experiments are that the slowing and deepening of respirations following unilateral vagotomy do not depend upon: (a) Passage of air in and out of the trachea. (b) Expansion and collapse of the lung. (c) Existence of a normal pulmonary circulation in the vagotomized lung. (d) Normal fluctuations in alveolar carbon dioxide tension, (e) Contraction and relaxation of the diaphragm on the side of vagotomy. 8. The slowing and deepening of respirations, alluded to, may be presumed to indicate that a normal reflex (the Hering-Breuer reflex) has been interrupted. Since this interruption occurs in spite of all the conditions enumerated under Paragraph 7, we must conclude that none of these conditions is essential to the existence of this reflex.

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