Current Status of Fibrinolysis for the Rapid Dissolution of Subarachnoid and Intraventricular Clot

Abstract

The half century coming to a close will hopefully have witnessed the discovery, description, elucidation, treatment and prophylaxis of a previously unknown disease entity — cerebral vasospasm from aneurysmal rupture and subarachnoid bleeding. Lysed red blood cells were shown to have vasoconstrictive activity in 1944. In 1949, autogenous erythrocytes incubated at body temperature for 4 days produced maximal pleocytosis in the spinal fluid of dogs as well as considerable protein elevation. During the same year it was shown in humans dying of ruptured aneurysms that almost one-third of cases showed cerebral infarcts consistent with temporary spasm of supplying vessels showing evidence of previously having been surrounded by blood clot. Two years later, cerebral vasospasm was demonstrated angiographically and it was shown to be a reversible process. The same year it was suggested that it would be logical to raise systemic blood pressure in patients having compromised cerebral hemodynamics following a variety of strokes. By the 1960’s it was generally accepted by neurosurgeons that the development of angiographic vasospasm was a prognostic factor for poor outcome. In that decade experimental studies showed that the application of autologous blood could cause primate arteries to go into spasm both acutely and chronically. The following 10 years witnessed the working out of the time course of vasospasm. It was demonstrated that spasm was not a continuous process that was present from the moment of aneurysmal rupture. Instead, it was seen to develop progressively over several days, reaching a maximum about 1 week following the aneurysmal rupture. Experimental evidence accumulated that vasospasm was related to exposure of cerebral arteries to erythrocyte breakdown products.