HEPARIN AND ASPIRIN IN THE TREATMENT OF HYPERACUTE REJECTION OF RENAL ALLOGRAFTS IN PRESENSITIZED DOGS

Abstract

SUMMARY Eleven pairs of dogs exchanged at least three skin grafts within the pairs until a “white graft” occurred and serum lymphocytotoxic antibody was demonstrated. Kidneys were then exchanged within the pairs. Six of eight kidneys in untreated dogs rejected by 12 hr, two within 36 hr. Four azathioprine-treated dogs rejected at 2, 4, 12, and 44 hr. Four dogs treated with heparin before and after transplantation did not reject hyperacutely. One animal received heparin at 15 min posttransplantation, but irreversible hyperacute rejection had already begun. Five aspirin-treated recipients did not reject acutely but were oliguric. Control grafts showed red cell aggregates in dilated peritubular and glomerular capillaries as early as 5 min. Fibrin-platelet microthrombi, swollen and vacuolated endothelial cells, and damage to arterial media were also early findings. By 24 hr, vascular thrombosis and cortical necrosis were evident. Aspirin-treated dogs showed similar but less severe changes. Heparin-treated dogs had only occasional intravascular red cell microaggregates but, by 4 days, cellular rejection was evident.