ABSTRACT
Angiographic studies performed within 6 hours of stroke onset have demonstrated that
75-80% of patients with an acute ischemic stroke have an angiographically visible
occlusion of an extracranial and/or intracranial artery that is the cause of the ischemic
stroke. The NINDS t-PA Stroke Study demonstrated that recanalization of occluded brain
arteries can successfully salvage ischemic brain if intravenous tissue plasminogen
activator (t-PA) is initiated within 3 hours of stroke onset. The effectiveness and
safety of intravenous t-PA beyond 3 hours has yet to be shown. Large clots in the
internal carotid artery, vertebral or basilar artery, or middle cerebral artery trunk
are infrequently lysed by intravenous t-PA during the first hour of treatment. In-traarterial
delivery of a thrombolytic agent appears to lyse clots in cerebral arteries more effectively
than intravenous t-PA. However, a head-to-head comparison of full-dose intravenous
t-PA and intraarterial therapy has yet to be done, and recanalization rates reported
in the intraarterial studies are at longer times after the start of therapy than the
rates of recanalization reported in intravenous t-PA studies. Intraarterial delivery
of thrombolytic therapy takes longer than intravenous delivery, and even intraarterial
delivery takes 2 hours on average to partially or completely lyse 75% of clots. Intraarterial
delivery of a thrombolytic agent has yet to be proven effective and safe in improving
long-term outcome of ischemic stroke patients. The approach of combining intravenous
and intraarterial delivery of t-PA or other pharma-cologic agents is an attractive
option that deserves further study. Mechanical lysis of clots, in combination with
pharmacologic therapies, is a more effective way to recanalize coronary arteries and
salvage heart muscle than intravenous thrombolytic therapy alone. This approach is
likely to be effective in ischemic stroke as well. What is needed is advances in catheter
technology that meet the special requirements of clot lysis in cerebral vessels. Whether
neuroprotective agents can extend the therapeutic window for effective clot lysis
and recanalization remains to be seen. Thrombolytic therapy and other pharmacologic
treatments of clot in cerebral vessels will likely remain a two-edged sword. Pharmacologic
therapies that increase the likelyhood of clot lysis and recanalization, such as thrombolytic
agents, the platelet Gllbllla receptor blockers, defibrinogenating agents, and even
the newer more potent thrombolytic agents, also concomitantly increase the risk of
bleeding into the brain. What we will be searching for in the coming decade is the
correct mechanical strategy, dose of a given pharmacologic agent, or combination of
agents that maximizes recanalization and minimizes the risk of intracerebral hemorrhage.
Keywords
acute stroke therapy - thrombolytic agents - t-PA - recanalization
