The knowledge obtained from the ongoing investigational trials of tPA for
acute ischemic stroke will not only help establish the appropriate dose range and complication rates but will also further develop the clearly mandatory rapid, aggressive team approach needed to truly treat
acute ischemic strokes successfully. Experimental
cerebral ischemia data have pointed to the need to treat acute clinical
stroke within only a few hours or less to effectively reduce
stroke morbidity and mortality. Specifically, with reversible MCA occlusion models of focal
cerebral ischemia (dogs and cats), the animals uniformly survive without neurological deficit if the occlusion is for less than 2 to 3 hours. Similarly in primates, MCA occlusion for 3 hours or less will lead to clinical improvement and a decrease in
infarct size, with complete recovery generally associated with less than 2 hours of MCA occlusion. Therefore, it appears unlikely that ischemic brain can be salvaged if vascular occlusion persists longer than 4 to 6 hours (similar to the pathophysiology of
myocardial ischemia). Further, at least one third of
ischemic stroke patients reperfuse spontaneously (and obviously too late) within 48 hours of
stroke onset. Several factors believed to be related to successful outcome after
thrombolytic therapy are summarized in Table 16. A schematic approach to determining the response to
thrombolytic agents in
acute ischemic stroke is outlined in Table 17. Zivin succinctly reviews thrombolysis for
stroke, both experimental and clinical, and summarizes some of the difficulties of the early clinical
stroke trials with
thrombolytic agents and speculates about future prospects. He believes tPA may prove valuable in the treatment of some forms of thromboembolic
stroke. Its usefulness may depend in part on how quickly the
drug can be initiated and the risk of side effects; factors that will require further study. The currently used doses of tPA may be too low to lyse large cerebral arterial clots and, therefore, if current trials do not show a positive treatment response, further trials with higher doses may be indicated. The implications of a potentially effective treatment for truly
acute stroke are enormous:
stroke will need to be considered by all (lay public through to caregivers) as a true medical emergency, analogous to MI and
trauma.(ABSTRACT TRUNCATED AT 400 WORDS)