y6 (140) Society for Experimental Biology and Medicine. 



in the liver of the dog as the result of injecting hemolytic immune 

 sera of high hemagglutinative power. 1 These necrotic lesions, 

 which are due apparently to an obstruction of the circulation by 

 thrombi composed of fused red blood-corpuscles, vary in position 

 and extent, according to the dose of serum administered. Small 

 doses cause more or less isolated lesions which may occupy any 

 portion of the lobule ; large doses produce a diffuse necrosis which 

 spares only the tissue about the larger portal spaces. The uni- 

 formity of this necrotic lesion suggested the -importance of a study 

 of the repair process which would naturally follow in animals 

 recovering from the acute toxic effects of the injected serum. The 

 extent of the destruction precluded complete regeneration of liver 

 parenchyma, and if the defect was repaired by connective-tissue 

 proliferation, the resulting histological picture would be, except for 

 a difference in the relation between the new tissue and the remainder 

 of the lobule, analogous to cirrhosis in man. 



Methods. — Dogs were injected either in the smaller branches 

 of the femoral vein, or in the abdominal cavity, with serum obtained 

 from rabbits which had received repeated injections of red blood- 

 corpuscles of the dog. The dose usually employed was 1 c.c. of 

 serum to from 500 gm. to 800 gm. of body- weight, and the ani- 

 mals were killed at intervals varying from 48 hours to 36 days 



Results. — A majority of the animals die after intervals varying 

 from 4 minutes to 48 hours. In those surviving, hemoglobinuria 

 was a constant phenomenon usually appearing within 18 to 24 

 hours, persisting 3 to 4 days, and followed for several days by the 

 presence of bile pigment in the urine. The first evidence of repair 

 was mitosis of the liver cells lying at a slight distance from the 

 necrotic areas. The earliest period at which this was seen was 38 

 hours after injection. At 48 hours the poliferation of endothelial 

 and connective-tissue cells was evident, and this increased so 

 rapidly that by the fifth day the necrotic tissue was largely re- 

 placed by young granulation tissue in the midst of which dividing 

 liver cells could be found in considerable number. The young 

 tissue later assumes a more fibrous appearance, the new blood-ves- 

 sels become prominent, and newly formed bile ducts appear in the 

 midst of the stroma. A development of liver cells from these 



1 Journal of Medical Research, 1904, xii, 329. 



