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 (99m)Tc-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 3-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 (AI). The AI was calculated as C(a)/C(b) x 100%, where C(a) represents the mean reconstructed counts for the ipsilateral ischemic area and C(b) 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 > or =4 points) at 24 hours, suggesting that recanalization occurred within 24 hours for almost all patients. AIs for the 25 irreversible lesions ranged from 15.0 to 53.4% (37.3 +/- 11.6%), whereas AIs for the 38 reversible lesions ranged from 45.0 to 83.1% (69.3 +/- 8.6%). There was a significant difference in the AIs for these two groups (P < 0.0001). The ischemia in tissue with AIs of more than 53.4% was reversible. In contrast, ischemic tissue with AIs of less than 45.0% could not escape cerebral infarction with our treatment. The ischemia in tissue with AIs between 45.0 and 53.4% was reversible in some patients and irreversible in others.

CONCLUSIONS

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.