Studies on the rejection of the transplanted homologous dog liver

Abstract

Dogs in which livers have been replaced with hepatic homografts usually die in 5 to 10 days. Liver metabolism is not detectably abnormal at first, but gradual deterioration of function commences on the fourth or fifth day. There was histologic evidence of rejection in all dogs dying after 4 days. This ranged from minimal mononuclear infiltration to almost complete destruction of parenchyma. In the longest survivor, 20 1/2 days, histologic changes were less profound than in many animals dying earlier. Widespread histologic changes were found in host reticuloendothelial system, involving the bone marrow, kidneys, lungs, lymph nodes, and other tissues. These consisted of fixed tissue proliferation and infiltration of mononuclear cells, principally plasma cells. These changes were thought to be due to a general host reticuloendothelial response to the antigenic stimulus of the homograft.

Fig. 1

Appearance of liver homografts at varying times after transplantation. At five days: left x42, right x263.

Fig. 2

Appearance of liver homografts at varying times after transplantation. At nine days: above x42, below x263.

Fig. 3

Appearance of liver homografts at varying times after transplantation. At ten days: above x42, below x263.

Fig. 4

Appearance of liver homografts at varying times after transplantation. At twenty and one-half days: above x42, below x263.

Fig. 5

Survival in dogs living more than 4 days. Note high mortality between fifth and tenth day.

Fig. 6

Blood sugars and bilirubins in 20½ day survivor (No. 65). Note improvement in chemistries after eleventh day.

Fig. 7

Fever and pulse of dog 76. Animal had no complications. Cause of death probably homograft rejection.

Fig. 8

Fasting blood sugars (dots) in all dogs not treated with intravenous glucose. Solid line connects average values for each day. Note that severe hypoglycemia sometimes developed as early as the fourth day.

Fig. 9

Scattergram showing pattern of onset of jaundice. Dots are individual total bilirubin determinations. Solid line connects average total bilirubin for each day. Dashed line represents the average of the corresponding direct bilirubin determinations. Note absence of chemical jaundice until sixth day.

Fig. 10

Alkaline phosphatase levels in 8 dogs. Note marked rise after fourth day.

Fig. 11

Total protein and albumin/globulin fractions in dog 65.

Fig. 12

Cholesterol and blood urea nitrogen in dog 65. Terminal uremia was seen in minority of animals.

Fig. 13

Mediastinal lymph node from dog 65. × 82. Note cortical thinning.

Fig 14

Host kidney from dog 76 showing: a, perivascular mononuclear aggregate of cells and vascular changes, × 232; b, cellular response in perirenal tissue, × 232. Aggregates were mostly plasma cells.

Fig. 15

Host lung from dog 68 showing proliferative process in alveolar septa, and giant cells. × 225.

Fig. 16

Bone marrow in dog 65, after 20½ days. × 392. Note large numbers of plasma cells.