MRI Demonstrates that Tissue-Type Plasminogen Activator Increases Stroke Volume if Cerebral Arteries Are not Successfully Recanalized

Abstract

The role of tissue-type plasminogen activator (rt-PA) during thromboly­sis of stroke is poorly understood. Recently, a direct neurotoxic effect of rt-PA was reported. This is at odds with studies that show an improved outcome. Here we inves­tigated the effect of rt-PA after failure to recanalize the occluded brain vessel. Sprague­Dawley rats underwent thromboembolic stroke. They were assigned to four groups according to the patency of the middle cerebral artery on cerebral x-ray angiography after treatment with saline or rt-PA (15 mg/kg body weight over 90 min, starting 1 h after embolization): (1) control without recanalization (n = 5), (2) rt-PA treatment without recanalization (n = 5), (3) control with spontaneous recanalization (n = 2), and (4) rt-PA treatment with recanalization (n = 3). Six sets of diffusion-and perfusion-weighted (bolus-track) magnetic resonance images were acquired throughout the 6-h observation period. When recanalization was successful, rt-PA sig­nificantly improved perfusion values and the final infarct size. However, final infarct volumes in nonrecanalized rt-PA-treated animals compared to control animals were 67.4% ± 5.4% versus 47.7% ± 17.9% of the ipsilateral hemisphere (P = 0.042) at corresponding perfusion values. Our results suggest that rt-PA treatment worsens outcome in a model of thromboembolic stroke if recanalization is not successful.