Hyperacute renal allograft rejection in the primate. Therapeutic limitations of antiplatelet agents alone and combined with heparin.
Two antiplatelet drugs, pyridinolcarbamate and Sudoxicam, were tested separately and in combination with heparin for their ability to modify experimental hyperacute renal allograft rejection in primates. Pyridinolcarbamate delayed and amerliorated tissue injury and obstructive thrombosis but only minimally prolonged renal blood flow over that seen in untreated allografts, suggesting that graft failure was primarily due to vasoconstriction. Sudoxicam, an antiinflammatory agent, resulted in higher initial blood flow, but the duration of flow and graft survival were again only minimally prolonged. However, functional changes including C3, Factor II and X consumption were prevented, a net increase in Factor VIII activity was minimized, and fibrinolysis was inhibited. The combined effects of pyridinolcarbamate and heparin resembled those of heparin alone. Combination of Sudoxicam with heparin was more effective than heparin along in preventing intrarenal complement consumption, sequestration of formed elements, activation of coagulation, and inhibition of fibrinolysis. However, the latter combination also failed to prolong venous flow and graft survival over that seen with heparin alone.
D000818:Animals; D002219:Carbamates / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000517:prevention & control*; D000882:Haplorhini; D006493:Heparin / Q000627:therapeutic use*; D007668:Kidney / Q000098:blood supply / Q000473:pathology; D016030:Kidney Transplantation; D008251:Macaca; D011727:Pyridinolcarbamate / Q000627:therapeutic use*; D013843:Thiazines / Q000627:therapeutic use*; D014184:Transplantation, Homologous
D002219:Carbamates; D013843:Thiazines; D011727:Pyridinolcarbamate; D006493:Heparin