Muscle extract infusion in rabbits. A new experimental model of the crush syndrome

Previous studies provide inconclusive data concerning the nephrotoxicity of myoglobin following muscle injury. We investigated the possibility that released muscle constituents other than myoglobin may be associated with renal damage, and studied accompanying hematological and coagulation changes. An extract of homologous or autologous muscle was infused intravenously in rabbits in a dose of 100 mg of muscle extract protein/kg; equine myoglobin was given to control animals. Experimental animals developed proteinuria, cylindruria, and a 50% reduction in glomerular filtration rate. Leukopenia, thrombocytopenia and evidence of intravascular coagulation also were seen. The muscle extract was shown to have thromboplastic activity; however inhibition of this by phospholipase C did not prevent the changes induced by muscle extract infusion possibly because the intrinsic changes coagulation pathway still was activated. Although moderate hypotension and ECG changes developed in some rabbits, these were not consistent and the renal functional changes appeared to be independent of these factors. Pulmonary and glomerular microthrombi were seen in experimental animals and there was vacuolation of the renal proximal tubular cells. The studies indicate that a number of biological systems are activated following muscle extract infusion and that these may be more important than the nephrotoxicity of myoglobin in the pathogenesis of the renal injury.