Relevance of focal cerebral ischemia models. Experience with fibrinolytic agents

Despite the limitations of individual ischemia models, experience with fibrinolytic agents suggests that 1) early intervention with rt-PA may result in rapid thrombolysis, functional recovery, and decreased mortality in small animal stroke thromboembolism models, 2) rt-PA has no general effect on clinical recovery following MCA occlusion and reperfusion in the nonhuman primate at dose rates capable of producing very high circulating rt-PA levels, while u-PA has an apparently salutary effect, and 3) intravenous infusion of rt-PA or u-PA early after ischemia/infarction in several model systems is not associated with significant intracerebral hemorrhage. The true clinical relevance of these general impressions must await the completion of human studies and studies in well-conceived models designed to define the vascular consequences to be expected from reperfusion achievable with thrombolytic agents.