Thresholds of ischemia salvageable with intravenous tissue plasminogen activator therapy: Evaluation with cerebral blood flow single-photon emission computed tomographic measurements

OBJECTIVE: This study investigated the cerebral blood flow (CBF) thresholds of ischemic cortices that were salvageable with intravenous tissue plasminogen activator (t-PA) infusion therapy. METHODS: We retrospectively reviewed data for 20 patients who were treated with intravenous low-dose (7.2 mg) native t-PA infusion therapy for distal embolic occlusions of middle cerebral artery divisions or branches, without early computed tomographic ischemic changes. All patients underwent pretreatment single-photon emission computed tomographic CBF measurements using Tc-99m-N,N'-(1,2-ethylenediyl)bis-L-cysteine diethylester. Intravenous t-PA infusion was initiated within 6 hours (average, 3 h) after symptom onset for 14 patients and 6 to 14 hours (average, 8.8 h) after the last time the patient was noted to be in normal condition for the other 6 patients. Pretreatment single-photon emission computed tomographic and S-month post-treatment computed tomographic scans were compared using computerized coregistration. Ischemic cortices in single-photon emission computed tomographic scans were divided into areas of reversible and irreversible ischemia. The degree of hypoperfusion was analyzed with an asymmetry index (Al). The Al was calculated as C-a/C-b x 100%, where C-a represents the mean reconstructed counts for the ipsilateral ischemic area and Cb represents the mean reconstructed counts for the corresponding contralateral area. RESULTS: Partial recanalization, with clinical improvement, at 60 minutes was confirmed by angiography for 14 of the 20 patients (70%). Seventeen of the 20 patients (85%) exhibited major neurological improvements (defined as decreases in National Institutes of Health Stroke Scale scores of greater than or equal to 4 points) at 24 hours, suggesting that recanalization occurred within 24 hours for almost all patients. Als for the 25 irreversible lesions ranged from 15.0 to 53.4% (37.3 +/- 11.6%), whereas Als for the 38 reversible lesions ranged from 45.0 to 83.1% (69.3 +/- 8.6%). There was a significant difference in the Als for these two groups (P < 0.0001). The ischemia in tissue with Als of move than 53.4% was reversible. In contrast, ischemic tissue with Als of less than 45.0% could not escape cerebral infarction with our treatment. The ischemia in tissue with Als between 45.0 and 53.4% was reversible in some patients and irreversible in others. CONCLUSION: To save ischemic tissue with our intravenous t-PA infusion therapy, residual CBF should be at least 45% of the contralateral presumed normal CBF value. CBF thresholds for ischemia that would be surely salvageable with our intravenous t-PA infusion therapy might be approximately 50 to 55% of the contralateral presumed normal CBF values.