Abstract

The fibrinolysin system is responsible for the dissolution of blood clots in vivo. Activation of the fibrinolysin system has been achieved by both enzymic and nonenzymic mechanisms. The mechanism of inducing and/or enhancing fibrinolytic activity by phrmacological agents has remained obscure. Phenformin was selected for study since its ability to induce fibrinolytic activity had been previously reported in patients with suppressed fibrinolytic activity. In rats rendered hypofibrinolytic by insulin pretreatment, phenformin produced a significant increase in fibrinolytic potential brought about by activation of plasminogen by an undetectable activator. This was accompanied by a reduction in the acid-labile inhibitors of plasmin and plasminogen activation and an increase in fast and slow antiplasmin levels. Acute administration of phenformin to normal control rats produced an overall suppression of the fibrinolysin system due to increased levels of fast antiplasmin and the acid-labile inhibitors of plasmin.