RESPIRATION BEYOND THE LUNGS 397 



corpuscles, which appear in large numbers in the blood under these con- 

 ditions. A similar increase in blood oxidation occurs during posthemor- 

 rhagic anemia, the rate of oxidation running parallel with the rate of 

 regeneration of the red corpuscles. 



The Mechanism by Which the Demands of the Tissues for 

 Oxygen Are Met 



There are two possible methods by which this may be brought about: 



(1) by a change in the C H or the saline constituents or the temperature of 

 the plasma, so that the hemoglobin more readily delivers up its load 

 of 2 ; and (2) by an increase in the mass movement of blood through 

 the vessels of the acting tissue. 



Kegarding the first of these possibilities, there is no doubt that acids 

 are produced during metabolism of acting tissues. As we have seen, 

 when muscles contract in the presence of an abundance of 2 , C0 2 is 

 produced in large amounts, and when they contract in a deficiency of 2 , 

 sarcolactic acid. In the submaxillary gland, too, it has been possible to 

 show that the C H of the venous blood, as measured by the value of K of 

 the dissociation curve of hemoglobin, becomes distinctly increased dur- 

 ing glandular activity. That this increase in C H will dislodge 2 we have 

 already seen (page 386). As to the possible influence of local changes 

 in temperature and in saline constituents of the plasma, nothing can at 

 present be said. 



Regarding the second possibility, vasodilatation may be dependent 

 either upon the action on the blood vessels of nerve impulses coming 

 along vasomotor nerves, or upon the production by the active tissue of 

 vasodilating or depressor substances (see page 243). Much evidence 

 has been accumulating in recent years which tends to show that such 

 depressor substances are produced, and they may be either (1) acids, or 



(2) organic bases of a similar nature to /3-imidazolylethylamine (hista- 

 mine). This latter substance is of considerable physiologic interest be- 

 cause of its close relationship to one of the main amino acids of the 

 protein molecule namely, histidine (see page 604). Its effect in pro- 

 ducing vasodilatation is extraordinary. Thus, half a milligram of the 

 drug injected intravenously into a monkey will lower the mean arterial 

 pressure by fifty per cent. 



But before such an hypothesis can be entertained, it is necessary to 

 show that, independently of nerve impulses, the blood vessels of an acting 

 organ may dilate. The best evidence has been secured by studying the 

 effects of stimulating with epinephrine the cervical sympathetic nerve to 

 the submaxillary gland of a cat. The gland cells become more active, 



