For how long is brain tissue salvageable? Thrombolysis-based evidence

Recombinant t-PA (tissue plasminogen activator, alteplase) was licensed for use in the United States for treatment of acute ischemic stroke on the basis of the National Institute of Neurological Disorders and Stroke (NINDS) study. In this trial, t-PA was started within 3 hours of onset of stroke symptoms. Two other trials of t-PA (the European Cooperative Acute Stroke Study [ECASS] I and ECASS II) failed to detect a significant effect in stroke patients. Both of these trials allowed treatment to begin up to 6 hours after the onset of symptoms. However, the results of a meta-analysis of all well-controlled trials of thrombolytics suggest that thrombolysis is an effective strategy when started up to 6 hours after the onset of symptoms. More than 50% of the trials included in this meta-analysis were, in fact, of t-PA. Allowing time for infusion of the thrombolytic and time for lysis of the thrombus, the findings of the meta-analysis suggest that salvageable tissue may remain for at least 8 hours after the onset of symptoms. Prourokinase was tested for efficacy in acute stroke in the PROlyse in Acute Cerebral Thromboembolism (PROACT) I trial. This trial had an insufficient number of patients to detect a meaningful effect. Consequently, the much larger PROACT II trial was conducted. In both of these studies, infusion began within 6 hours of the onset of symptoms. PROACT II demonstrated a significant improvement in outcome, and it can be concluded that, in some patients at least, salvageable tissue remained for at least 8 hours after the onset of symptoms. Consequently, treatment with a neuroprotectant during this 8-hour window might have been effective.