Myocardial depressant factor and circulatory shock

MDF is a small peptide, having a molecular weight of 500–1000 that is produced in the ischemic pancreas during a variety of types of circulatory shock. It is probably produced by the proteolytic degradation of intracellular pancreatic protein by the combined action of lysosomal and zymogenic proteases. MDF is transported to the circulation by lymphatics and by systemic microcirculatory vessels. MDF depresses contractility of the heart under a variety of hemodynamic conditions. It also constricts splanchnic resistance vessels thereby favoring its production. Moreover, this toxic peptide contributes to reticuloendothelial phagocytic depression thus hampering its clearance from the circulation. Glucocorticoids and certain protease inhibitors are very effective pharmacological agents in preventing the formation of MDF. Conventional inotropic agents are not ideal agents in shock since they usually exert undesirable side effects which cancel much of their useful inotropic action. Surgical interventions such as pancreatic duct ligation, pancreatectomy, pancreatic vascular perfusion, thoracic lymph duct diversion or hemodialysis can prevent the formation, transport, or biological actions of MDF in animals, but they are impractical and difficult to perform in patients during shock. MDF is a toxic factor that contributes to the lethality of the shock state by virtue of its positive feedback actions. Moreover, lysosomal hydrolases which are released into the circulation during shock are directly deleterious to the organism, and also sensitize the circulatory system to the deleterious effects of MDF. Further work is needed to determine the complete chemical identity of MDF and to evaluate its detailed mechanism of action in shock states. Therapeutic measures specific for the antagonism of MDF would be a desirable and useful tool in the overall therapeutics of many types of circulatory shock.