570 CIRCULATION OF BLOOD AND LYMPH. 



produced, and we speak of it as the inner stimulus. Experiment and 

 speculation have been directed toward unraveling the nature of 

 this inner stimulus. Most of the physiologists who have expressed 

 an opinion upon the subject have sought an explanation in the 

 composition of the blood or lymph bathing the heart tissue, or in the 

 products of metabolism of the tissue itself. Regarding this latter 

 view there is nothing of the nature of direct experimental evidence 

 in its favor. No product of the metabolism of the heart tissue 

 capable of exerting this stimulating effect has been isolated. In 

 regard to the former view, that the inner stimulus is connected 

 with a definite composition of the blood or lymph, there has been 

 considerable experimental work which is of fundamental signifi- 

 cance. While the older physiologists paid attention mainly to the 

 organic substances in the, blood, it has been shown in recent years 

 that the inorganic salts are the elements whose influence upon 

 the heart beat is most striking. These salts are in solution in the 

 liquid of the tissue, and are therefore probably more or less com- 

 pletely dissociated. Attention has been directed mainly to the 

 influence of the cations, of which three are especially important, 

 namely, the sodium, the calcium, and the potassium. 



The Action of the Calcium, Potassium, and Sodium Ions in 

 the Blood and Lymph. It has long been known that the heart 

 of a frog or terrapin may be kept beating normally for hours after 

 removal from the body, provided it is supplied with an artificial 

 circulation of blood or lymph, so arranged that this liquid enters 

 the heart through the veins from a reservoir of some sort and is 

 pumped out through the arteries leading from the ventricle. It 

 was first shown by Merunowicz, working under Ludwig's direction, 

 that an aqueous extract of the ash of the blood possesses a similar 

 action. 



Ringer afterwards proved that the frog's heart can be kept 

 beating for long periods upon a mixture of sodium chlorid, potassium 

 chlorid, and calcium phosphate or chlorid, and he laid especial 

 stress upon the importance of the calcium. This work was after- 

 wards confirmed and extended by others, who attempted to 

 analyze the part played by the several ions.* If a frog's or a 

 terrapin's heart is fed with a solution of physiological saline 

 (NaCl, 0.7 per cent.) it beats well for a while, but the beats 

 soon weaken and gradually fade out. If in this condition the 

 heart is fed with a proper mixture of sodium, potassium, and 

 calcium chlorids it beats vigorously and well for very many 



* For literature and discussion see Ho well, "American Journal of Phys- 

 iology," 2, 47, 1898, and 6, 181, 1901, and "Journal of the American Medical 

 Association," 1906. Burridge, "Quarterly Journal of Exp. Physiology," 5, 

 347, 1912. 



