Respiration and Metaholisui 255 



and the expiiator\ phase, inasmuch as extreme inspiration results in greater 

 excitation of the inspiratory center to provide a short additional respirators- 

 spurt, and extreme expiration causes stimulation of "deflation" receptors by 

 which the succeeding inspiration is augmented more forcibly than it would be 

 otherwise. 1 he cells of the respiratory center show considerable \ariation in 

 threshold, thereby permitting a graded response to increased stimulation. Only 

 a few fibers are active in eupnea, but with the proper respiratory stimulation 

 less excitable neurones react, and the impulse frequency of all the fibers in- 

 creases. In general the threshold of the expiratory neurones is higher than that 

 of the inspiratory neurones. I he medullary respiratory center initiates and 

 coordinates respiration by sending out a constant flow of impulses which are 

 rhythmically interrupted by the Hering-Breuer reflex mechanism and, in 

 extreme hyperventilation, by the pontine pneumotaxic center as well. 



Wartime studies on pressure breathing, accomplished by means of facial 

 masks to increase the ambient pressure, demonstrate that inspiration becomes 

 passive and expiration is necessarily acti\e, under these conditions, with a 

 respiratory pause following inspiration. ''' 



The respiratory center is affected directly by a number of agents, including 

 carbon dioxide increase in arterial blood (the most important), increased 

 acidity of the blood, oxygen lack, rate of blood flow, and temperature. Response 

 of the center to increases in arterial carbon dioxide is the most delicate mech- 

 anism controlling breathing. A decrease in sensiti\iiy of the center to carbon 

 dioxide is frequently a concomitant of abnormal conditions and may result in 

 Cheyne-Stokes breathing or, under sexere anesthesia (morphine), in complete 

 cessation of xentilation.^"*^ In man and dogs increased tolerance may be estab- 

 lished to carbon dioxide atmospheres of 3 per cent and greater.^ '^ On the other 

 hand, an increase in carbon dioxide sensitivity is indicated in cases of acido- 

 sis.''*"' 



The action of carbon dioxide on the respiratory center is known to be a 

 direct one, but the mechanism is not clear. The older hypothesis of Winter- 

 stein'^^ and Ilaldane^'""' regarded the main action of carbon dioxide to be its 

 acid-producing capacity, the stimulus taking effect through the hydrogen 

 ions resulting from the dissociation of carbonic acid. Carbon dioxide per se 

 has been considered more effective than other hydrogen ion-producing sub- 

 stances and has come to be regarded as having a specific effect on the respira- 

 tory center.-''^' •"*' However, Gray^^- finds that alveolar ventilation seems to 

 depend on the sum of the stimulating effects of blood COo and of hydrogen 

 ion. GeselP-'"' '-" suggests that carbon dioxide penetrates the cells of the 

 respiratory center, where it gives rise to excitatory hydrogen ions. Considerable 

 evidence favors the action of carbon dioxide itself as a specific stimulant of 

 the center, but the action of hydrogen ions acting under some conditions can- 

 not be disregarded. 



The activity of the respiratory center is modified, particularly in times of 

 respiratory stress, by reflexes originating in the chemoreceptors of the aortic 

 and carotid bodies. These end-organs are particularly responsive to decreases 

 in oxygen tension of the blood, and less responsive to increased acidity and 

 carbon dioxide tension. The important role of chemoreception was beautifully 

 demonstrated by the notable work of Heymans and his colleagues."'^ Largely 

 through the work of the Belgian group, it is recognized that chemoreception 



