Serum Nephritis I N Rabbits

Administration of heparin before the induction of nephrotoxic serum nephritis in rabbits decreases the incidence of crescent formation and glomerular sclerosis (Halpern, Milliez, Lagrue, Fray 8c Morard, 1965). Anticoagulation with a dicoumarol also decreases the amount of intraglomerular fibrin deposition (Vassalli 8c McCluskey, 1964), and it has been postulated that fibrin deposition may be an important factor in the pathogenesis of some features of glomerular damage in this disease. It is known, however, that heparin has a number of other effects apart from that of anticoagulation, such as anticomplementary and histamine binding activity. Neither heparin nor dicoumarols directly inhibit the conversion of fibrinogen into fibrin but act at earlier stages in the coagulation cascade. To investigate the role of fibrin deposition more precisely, and eliminate, as far as possible, effects on other pathogenetic mechanisms, the circulating amount of fibrinogen in animals given the disease has been decreased to extremely low values by the intravenous administration of Arvin. This causes the intravascular formation of unstable fibrin polymers which are sequestered mainly in the lungs and reticulo-endothelial system and undergo rapid lysis with no apparent harmful effect on renal or other organ function. As the only significant effect of Arvin that has been shown to occur is one of defibrination, its effects on nephrotoxic serum nephritis may be expected to indicate only that part played by fibrin deposition in the pathogenesis of the glomerular damage.