REPERFUSION AFTER THROMBOLYTIC THERAPY OF EMBOLIC STROKE IN THE RAT -MAGNETIC-RESONANCE AND BIOCHEMICAL IMAGING

The effect of thrombolytic therapy was studied in rats submitted to th romboembolic stroke by intracarotid injection of autologous blood clot s. Thrombolysis was initiated after 15 minutes with an intracarotid in fusion of recombinant tissue-type activator (10 mg/kg body weight). Re perfusion was monitored for 3 hours using serial perfusion-and diffusi on magnetic resonance imaging, and the outcome of treatment was quanti fled by pictorial measurements of ATP, tissue pH, and blood flow. In untreated animals, clot embolism resulted in an immediate decrease in blood flow and a sharp decrease in the apparent diffusion coefficient (ADC) that persisted throughout the observation period. Thrombolysis s uccessfully recanalized the embolized middle cerebral artery origin an d led to gradual improvement of blood flow and a slowly progressing re versal of ADC changes in the periphery of the ischemic territory, but only to transient and partial improvement in the center. Three hours a fter initiation of thrombolysis, the tissue volume with ADC values les s than 80% of control was 39 +/- 22% as compared to 61 +/- 20% of ipsi lateral hemisphere in untreated animals (means +/- SD, P = .03) and th e volume of ATP-depleted brain tissue was 25 +/- 31% as compared to 46 +/- 29% in un treated animals. Recovery of ischemic brain injury afte r thromboembolism is incomplete even when therapy is started as early as 15 minutes after clot embolism. Possible explanations for our findi ngs include downstream displacement of clot material, microembolism of the vascular periphery, and events associated with reperfusion injury .