ABSTRACT
The rationale for acute intervention in ischemic stroke derives from the observation that ischemic stroke is a thrombotic vascular disorder with neurological consequences. Among the important unknowns present at the inception of studies of acute stroke intervention in the late 1970s/early 1980s were how ischemic injury leads to infarction and whether conditions could be developed by which arterial reperfusion could improve injury outcome (del Zoppo et al., 1986). With the rst clinical studies, animal model systems had not yet been fully developed to address these pathophysiologic issues. Acute intervention with thrombolytic agents (plasminogen activators [PAs]) has so far proved central to the reduction of residual injury in patients presenting with thrombotic or thromboembolic stroke (Mori et al., 1992; Hacke et al., 1995; The National Institutes of Neurological Disorders and Stroke rt-PA Stroke Study Group, 1995). The change in conceptual framework from intransigence in treating ischemic stroke patients to acute intervention, growing experience with PAs in this setting, and the application of new methodologies for their delivery were necessary steps in the learning curve to provide the new therapeutic possibilities. Each of these elements provided criteria for studying these acute thrombolytic approaches in ischemic stroke patients in a prospective fashion and has contributed to the clinical trial formats that have been employed to demonstrate safety and efcacy. Differences between local and systemic infusion techniques and their clinical setting have also underscored important limitations to acute treatment of brain-supplying arterial occlusions presenting as abrupt onset symptoms and the rules to be used for their clinical study. The heterogeneity among the trials, their populations, and outcomes is addressed in the Cochrane Collaboration reviews on acute thrombolysis (Wardlaw et al., 2009).
