388 RETROGRESSIVE CHANGES 



animals, either of the same species as that from which the pancreas 

 was obtained, or into a foreign species. Commercial "pancreatins" 

 were also quite effective, whether in weak acetic acid or weak alkaline 

 solutions. The power of these materials to cause fat necrosis was 

 reduced by heating to or above 60° for five minutes, and completely 

 destroyed at 71°, indicating that the active agent is an enzyme. But, 

 as in the same material trypsin was injured by temperatures above 60°, 

 and destroyed at between 70° and 72°, and lipase was weakened above 

 50°, and destroyed above 70°, it was impossible to determine, by 

 heating pancreatic preparations, whether the lipase or the trypsin 

 was the essential factor. By permitting pancreatic extracts to digest 

 themselves it was found that the power to produce fat necrosis 

 decreased, pari passu, with the decrease in lipolytic strength. Prepara- 

 tions strongly tryptic, but very weak in lipase, produced no fat necro- 

 sis, and, on the other hand, extracts of pig's liver or of cat's serum, 

 both rich in lipase but devoid of trypsin, were equally ineffective. 

 Furthermore, mixtures of hver or serum lipase and trypsin were 

 incapable of causing fat necrosis. Fresh pancreatic extracts from 

 fasting dogs, containing lipase but almost no trypsin (which in fresh 

 extracts is still in the form of inactive trypsinogen), produced abun- 

 dant fat necrosis, whereas after the trypsinogen in such extracts was 

 activated by enterokinase, no fat necrosis could be produced. It 

 therefore seems certain that trypsin alone cannot produce fat necrosis, 

 and that the decrease in strength of lipase in a pancreatic extract is 

 associated with a corresponding decrease in power to produce fat 

 necrosis. But, on the other hand, lipase of liver or blood-serum alone, 

 or when mixed with trypsin, will not produce fat necrosis. The possi- 

 bility remains that pancreatic lipase is different from liver or serum 

 lipase, and can by itself cause fat necrosis; more probably, however, 

 the production of fat necrosis depends upon a double action, trypsin 

 causing the death of the cells, and lipase splitting the fat?.^" The 

 fatty acids alone will not cause necrosis of fat-cells, and it was shown 

 that the first steps in the process consist of a necrosis of the surface 

 endothelium extending into the connective and fat tissue; this may 

 occur in a few minutes, while evidence of fat-splitting can be obtained 

 only after about three hours, and the splitting occurs only in cells 

 that have already become necrotic; hence the fat-splitting is not the 

 cause of the necrosis, but occurs subsequent to the necrosis. After 



^° When fat tissue dies in the body from other causes, the lipase normally con- 

 tained within the fat tissue does not cause the changes seen in fat necrosis. It is 

 possible, therefore, that the combining of newly split fatty acids by the alkali of 

 the pancreatic juice is responsible for the formation of the large amount of soaps 

 found in fat necrosis. Otherwise we might expect the lipase to produce only 

 an equilibrium, and that, in the case of fat, seems to exist when most of the sub- 

 stance is neutral fat. In support of this idea 1 found that strong alkalies injected 

 into fat tissue sometimes caused changes very closely resembling areas of fat 

 necrosis in the early stages. 



