Successful short-term modification of hyperacute renal allograft rejection in the primate. Intrarenal effects of phenoxybenzamine and methylprednisolone combined with heparin

Abstract

Inhibition of renal vasoconstriction during hyperacute rejection by phenoxybenzamine or methylprednisolone combined with either the antiplatelet agent pyridinolcarbamate or heparin was evaluted in primates. Phenoxybenzamine plus pyridinolcarbamate did not prolong kidney survival. Phenoxybenzamine plus heparin uniformly prolonged low rates of venous flow to 180 minutes and delayed secondary C3 consumption, sequestration of erythrocytes and platelets, coagulation, and fibrinolysis; neutrophil sequestration and vascular injury and obstruction were more marked than with heparin alone. Host pretreatment with methylprednisolone plus heparin also prolonged the low rates of venous flow to 180 minutes, further reduced secondary alterations, and resulted in the least vascular injury. When intact donor kidneys were also pretreated with methylprednisolone, persistently normal rates of venous flow were achieved. Despite marked consumption of Factor XII, the consumption of C3, other coagulation factors, prekallikrein, and sequestration of formed elements was minimal, and the histology appeared compatible with even more prolonged survival.