HISTORICAL DEVELOPMENT 6 



The studies of Embden and his collaborators in Germany from 1914 to 

 1921 showed that the increased acidity of muscles stimulated under anaer- 

 obic conditions, or in contracture, is due to the accumulation of lactic and 

 phosphoric acids derived from the phosphorylated products of carbohydrate 

 metabolism, and it was believed furthermore that contractions and contrac- 

 tures might be due to this acid produced, the acidity altering the colloidal 

 state of the muscle proteins. Von Fiirth (1919) in his review of muscle 

 physiology stated that bromoacetate contracture is due to an explosive 

 formation of lactic acid. The reports by Schwartz and Oschmann (1924, 

 1925) that neither lactic nor phosphoric acid accumulated in muscles put 

 into contracture by bromoacetate, indicating that this type of contracture 

 is different from others, went without notice. 



The turning point in this aspect of muscle physiology came with the 

 work of Lundsgaard (1930 a) in the Institute for Medical Physiology at the 

 University of Copenhagen, and these studies not only established some basic 

 concepts of muscle contraction but introduced iodoacetate into general use. 

 Lundsgaard confirmed the effects of bromoacetate in frogs and rabbits but 

 found iodoacetate to be more potent. The intravenous injection of iodo- 

 acetate at 50 mg/kg into rabbits produced a sudden development of general 

 muscle rigor before death, the animals becoming "starr wie ein Stuck Holz" 

 whereas frogs could live for several hours after the onset of rigor. The basic 

 contribution of Lundsgaard lies in his demonstration that iodoacetate inhib- 

 its the formation of lactate in muscles under a variety of conditions, and 

 that muscles so poisoned retain the ability to contract until they go into 

 rigor. He found frog muscles in situ to contain 57 mg% lactate normally 

 but only 39 mg% after injection of iodoacetate. Muscles standing for 2 hr 

 contain high concentrations of lactate (649 mg%) whereas iodoacetate- 

 treated muscles under the same conditions contain very little lactate (27 

 mg%). If the muscles removed from iodoacetate-poisoned frogs were stim- 

 ulated to contract, no more lactate was found in them than in those muscles 

 allowed to rest. As the muscles were stimulated, the contractile amplitude 

 decreased and contracture soon ensued although lactate was not formed, 

 as shown in the accompanying tabulation. The poisoned muscle will con- 



tract without formation of lactate and do as much work as a normal muscle 

 producing 50-60 mg% lactate. If lactate is not responsible for contractions 



