Combined fibrinolytic and anticoagulant therapy improves early recanalization but not cerebral perfusion. C57BL/6 mice were subjected to the iCAT stroke model (60 minutes’ ischemia). Treatments were delivered IV 15 minutes after occlusion of the carotid artery (supplemental Figure 2E). Treatment dosing regimens: rtPA (10 mg/kg [1/9 mg/kg bolus/infusion over 30 minutes]); argatroban (80 µg/kg bolus; 40 µg/kg per minute infusion over 60 minutes + osmotic minipump 40 µg/kg/min infusion 23 hours). Blood flow was monitored for 60 minutes after treatment onset, and recanalization defined as measurable return of blood flow, classified as: stable (steady flow), unstable (fluctuating flow), transient with reocclusion, or none, as defined in the supplemental Methods. (A) Graph represents the percentage of animals exhibiting each specified category of blood flow, where n represents the total number of animals in each cohort. Recanalization data in the rtPA and rtPA/argatroban cohort represent pooled data from separate experimental cohorts. (B) Graph represents the amount of time vessels remain patent, quantified as a function of the area under the curve for rtPA and rtPA/argatroban cohorts. (C) A subset of animals was recovered to 24 hours for assessment of stroke outcomes (Recanalization details of this cohort alone are provided in supplemental Figure 4.) Cerebral perfusion (LSCI) was assessed at 90 minutes’ post–stroke onset in sham (n = 4) and control (n = 8) animals or in animals treated with rtPA (n = 8) or rtPA/argatroban (n = 14) from a single experimental cohort. Animals that died before the 90-minute time point were not included in cerebral perfusion assessment. Quantification of ipsilateral cerebral perfusion at 90 minutes’ post–stroke onset is presented in a boxplot depicting the middle 50% (box) and minimum to maximum data values obtained (whiskers), with all data points shown for clarity. Statistical analysis was performed by using an ordinary one-way analysis of variance with Tukey’s multiple comparisons test, where ***P < .001, **P < .005 and ^nsP > .05. Cohort mortality Skull and crossbones ([skull and crossbones]) denote mortality rate as a percentage of animals treated (sham, n = 8; vehicle, n = 8; rtPA, n = 8; rtPA/argatroban, n = 14). ns, not significant.