PHYSIOLOGY AND BIOCHEMISTRY OF SHOCK 419 



to agree with the present concept of the functions of choHnergic nerves. 

 The diffuse and intense pain may have resulted from generalized 

 stimulation of nerve endings subserving pain. 



f . In Vitro Action of Acetylcholine on Muscle Contraction. It has 

 been reported that the proximate intra-arterial injection of minute 

 amounts (2 /^g) of acetylcholine into mammalian skeletal muscle 

 produces a pow^erful twitch equal in tension to that induced by a 

 single maximal motor nerve volley (Brown, Dale and Feldberg, 1936). 

 According to Brown (1937, discussed by Nachmansohn, 1945) the 

 amount of acetylcholine necessary to produce a maximal twitch of 

 striated muscle is 100,000 times as high as that liberated per nerve 

 stimulus. It may also be noted that the concentration of cholinesterase 

 at the motor end-plates is many thousand fold higher than in the whole 

 muscle, which would mean that the rate of hydrolysis of acetylcholine 

 at motor end-plates is equally greater than in the whole muscle. 



Cantoni and Eastman (1946) reported that the administration of 

 histamine (1:100 million), acetylcholine (1:10 million), pilocarpine 

 (1 : 100,000), barium chloride and acetyl-i^-methylcholine was followed 

 by temporary depression of the contractile responsiveness of the in- 

 testinal strip of the guinea pig. On the other hand, a maximal contrac- 

 tion in response to large doses of potassium chloride did not result 

 in a decreased contractility of the preparation. In fact, a small increase 

 in the K/Ca ratio of the perfusion fluid was sufficient to neutralize the 

 eff"ect of large doses of histamine, acetylcholine, pilocarpine, and 

 barium chloride. 



Potassium ion is essential for the phosphorylation of pyruvic acid 

 in the presence of an adequate concentration of adenosine triphosphate 

 (ATP). The formation of phosphopyruvate is a necessary step for the 

 synthesis of (a) glycogen, and (b) phosphocreatine. In the synthesis 

 of phosphocreatine, phosphopyruvate immediately transfers its phos- 

 phate to creatine, ATP^^ADP (adenosinediphosphate) acting as inter- 

 mediate link. 



Pyruvic acid -|- ATP -1-K+ ^ phosphopyruvate-]- ADP 

 Phosphocreatine-f-ADP ^ ATP-|-creatine. 



In muscle contraction, the breakdown of ATP is believed to be the 

 most probable immediate source of energy. According to Buchthal, 

 ei al. (1946) creatine phosphate and acetylphosphate have no eflfect 



