Tissue at risk of infarction rescued by early reperfusion: A positron emission tomography study in systemic recombinant tissue plasminogen activator thrombolysis of acute stroke

Thrombolytic therapy of acute ischemic stroke can be successful only as lon g as there is penumbral tissue perfused at rates between the thresholds of normal function and irreversible structural damage, respectively. To determ ine the proportion of tissue at risk of infarction, cerebral perfusion was studied in 12 patients with acute ischemic stroke who underwent treatment w ith systemic recombinant tissue plasminogen activator (0.9 mg/kg body weigh t according to National Institute of Neurological Disorders and Stroke prot ocol) within 3 hours of onset of symptoms, using [O-15]-H2O positron emissi on tomography (PET) before or during, and repeatedly after thrombolysis. Th e size of the regions of critically hypoperfused gray matter were identifie d on the initial PET scans, and changes of perfusion in those areas were re lated to the clinical course (followed by the National Institutes of Health stroke scale) and to the volume of infarcted gray matter demarcated on mag netic resonance imaging 3 weeks after the stroke. Whereas the initial clini cal score was unrelated to the size of the ischemic area, after 3 weeks the re was a strong correlation between clinical deficit and volume size of inf arcted gray matter (Spearman's rho, 0.96; P < 0.001). All patients with a s everely hypoperfused fused (< 12 mL/100 g/min) gray matter region measuring less than 15 mt on first PET showed full morphologic and clinical recovery (n = 5), whereas those with ischemic areas larger than 20 mt developed inf arction and experienced persistent neurologic deficits of varying degree. I nfarct sizes, however, were smaller than expected from previous correlative PET and morphologic studies of patients with acute stroke: only 22.7% of t he gray matter initially perfused at rates below the conventional threshold of critical ischemia became necrotic. Actually, the percentage of initiall y ischemic voxels, that became reperfused at almost normal levels clearly p redicted the degree of clinical improvement achieved within 3 weeks. These sequential blood flow PET studies demonstrate that critically hypoperfused tissue can be preserved by early reperfusion, perhaps related to thrombolyt ic therapy. The results correspond with experimental findings demonstrating the prevention of large infarcts by early reperfusion to misery perfused b ut viable tissue.