Abstract
Kidneys of 12 heparinized rabbits were perfused with the fresh venous heparinized blood of two healthy human volunteers for 30 s, 1, 2, 5, 15, and 30 min. The renal lesion was investigated by optical, electron, and immunofluorescence microscopy. After 30-s perfusion the first signs of local human IgG fixation appeared, and after 1 min, positive staining for complement (C 4, C 3) was recorded. The intensity of fluorescence increased up to 2 and 5 min, and was strongest on the inner surfaces of arterial vessels. Weaker focal and segmental linear fluorescence was found in glomerular and peritubular capillaries. Anti-human-IgA and -IgM yielded discrete and sporadic fluorescence, while IgD, IgE, and C 1q were always negative. Anti-rabbit-Ig exhibited only vague fluorescence in the arterial adventitia and discrete linear positivity in glomerules, and reacted in perfused as well as in control non-perfused kidneys. Ultrastructurally, moderate focal platelet aggregation appeared after only 30-s perfusion. After 5 min the most striking feature was extensive disorganization with disruption of capillary and arterial and arteriolar endothelium and focal cell sloughing, without apparent topographic relation to platelet aggregation or leukostasis. The disruption of the endothelia and intracapillary blood elements became diffuse and massive after 15 and 30 min; in capillaries focal granular masses and sparse networks reactive with anti-human-fibrin and -fibrinogen appeared. Typical occlusive thrombosis was not found. The most salient feature of blood xenoperfusion was immediate vascular fixation of human antibodies and of complement, with probable “classical” activation of the latter. Extensive endothelial destruction followed within several minutes. Man thus rejects xenografts as effectively as lower mammals.
Published Version
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