Stroke, Vol 21, 596-601, Copyright © 1990 by American Heart Association
GJ del Zoppo, BR Copeland, K Anderchek, W Hacke and JA Koziol
The effect of an intravenous infusion of recombinant tissue plasminogen
activator on hemorrhagic transformation early after middle cerebral artery
territory ischemia was studied in an established awake nonhuman primate
(baboon) model. Following 3 hours' occlusion of the middle cerebral artery
and 30 minutes' reperfusion in each of 30 baboons, a 60- minute infusion of
recombinant tissue plasminogen activator (at three doses: Group A, 0.3
mg/kg, n = 6; Group B, 1.5 mg/kg, n = 6; Group C, 10 mg/kg, n = 6) or
normal saline (n = 12) was undertaken. The frequency and volume of
intracerebral hemorrhage, the volume of infarction, and clinical
alterations were determined by computed tomography at 24 hours and 10 days,
neuropathology at 14 days, and serial daily neurologic evaluations,
respectively. Peripheral (nonintracranial) hemorrhage (Group A, p = 0.46;
Group B, p = 0.015; Group C, p = 0.002) and peak plasma tissue plasminogen
activator levels varied directly with the dose of recombinant tissue
plasminogen activator. Petechial hemorrhagic infarction was a common
finding among the 30 baboons. No significant differences in the incidences
or volumes of infarction-related hemorrhage were apparent in any group
compared with the respective saline-treated baboons. In pooled data, no
significant relation between the volume of hemorrhage and the volume of
infarction could be established. We conclude that the incidence and
severity of hemorrhagic transformation are not related to infarction size
and that recombinant tissue plasminogen activator does not increase the
incidence or severity (volume) of hemorrhage when given early (less than or
equal to 3.5 hours) after the onset of focal cerebral ischemia in this
model.
ARTICLES
Hemorrhagic transformation following tissue plasminogen activator in experimental cerebral infarction
Department of Molecular and Experimental Medicine, Scripps Clinic and Research Foundation, La Jolla, California 92037.
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