ESTABLISHMENT OF AN ANIMAL-MODEL FOR MYOGLOBINURIA BY USE OF A MYOTOXIN FROM PSEUDECHIS-AUSTRALIS (KING BROWN SNAKE) VENOM IN MICE

A new laboratory animal model for studying the pathologic mechanisms o f myoglobinuria in mice after envenomation with Pseudechis australis s nake venom or its myotoxin has been established. The experimental mice (Swiss albino) had myoglobinuria 60 min after administration of the v enom, as indicated by red or dark-brown urine. Light microscopic studi es revealed myonecrosis of the locally injected soleus muscle 30 min a fter exposure to the myotoxin, followed by regeneration in 7 to 10 day s. Electron microscopic studies of the soleus muscle revealed fragment ation and dissolution of the Z disk, followed by degeneration of the s arcomere. Light microscopy of the kidneys revealed numerous pigmented casts filling the lumen of the tubules; some tubules had features of a cute tubular necrosis. Immunohistochemical localization of myoglobin b y the immunoperoxidase method confirmed myoglobin casts in the renal t ubules. Electron microscopy of the kidneys also revealed intratubular casts composed of markedly electron-dense material filling the lumen. These results indicate that rhabdomyolysis caused by the venom or toxi n is followed by myoglobinuria, with renal manifestations in the form of myoglobin cast nephropathy and tubulopathy. This mouse model of exp erimental snake venom-induced myoglobinuria is an ideal model for inve stigating the entire sequence of myoglobinuria and related cast nephro pathy.