The Use of Fibrinolytic Therapy in Acute Ischemic Events

Abstract

The loss of tissue perfusion represents the pathological basis underlying acute cerebrovascular events. The occlusion of the brain's blood supply by intravascular thrombotic and/or atherosclerotic phenomena results in a disruption in tissue oxygen and glucose delivery. This inevitably impairs the cell's capacity to synthesize ATP. Despite initial attempts to maintain consistent ATP stores through anaerobic glycolysis and adenosine release, the starving tissue experiences loss of membrane ionic gradients, secondary to the inactivation of the Na+/K+ ATPase pump. A significant increase in intracellular calcium concentration is triggered by the activation of voltage- gated calcium channels, the activation of ligand-gated calcium channels, and by the inactivation of the Na+/Ca+ exchanger. In addition, massive release of the main excitatory, inhibitory, and monoamine neurotransmitters (many of which become excitotoxins at high concentration) is also observed. The above excitatory transmitters, such as glutamine, for example, play an important role in the over-stimulation of the NMDA receptor, which in turn promotes excessive calcium influx (1). The cytotoxic effects of calcium are associated with the activation of lipases, proteases, and endonucleases, as well as xanthine oxidase and neuronal NO synthase, capable of either direct or indirect destruction of cellular structures (2).