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(Stroke. 2001;32:1336.)
© 2001 American Heart Association, Inc.

Original Contributions

Hemorrhagic Transformation After Fibrinolysis With Tissue Plasminogen Activator

Evaluation of Role of Hypertension With Rat Thromboembolic Stroke Model

Emiri Tejima, MD; Yoichi Katayama, MD, PhD; Yasuyuki Suzuki, MD; Tsuneo Kano, MD, PhD Eng H. Lo, PhD

From the Department of Neurological Surgery (E.T., Y.K., Y.S., T.K.), Nihon University School of Medicine, Tokyo, Japan, and the Neuroprotection Research Laboratory (E.H.L.), Departments of Neurology and Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, Mass.

Correspondence to Dr Tsuneo Kano, 30-1 Oyaguchi Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan. E-mail tsuneok{at}med.nihon-u.ac.jp

Background and Purpose—We used a rat model of thromboembolic stroke to evaluate whether hypertension increases the incidence of hemorrhage after fibrinolysis with tissue plasminogen activator (tPA).

Methods—In this model, a microclot suspension was injected into the middle cerebral artery territory to induce focal ischemia. Reperfusion was induced in spontaneously hypertensive rats (SHR) by administering tPA (10 mg/kg) intravenously at 2 hours or 6 hours after the onset of thromboembolic focal ischemia. In untreated control rats, saline was administered at 2 hours after ischemia.

Results—Hemorrhagic transformation was observed only in rats that received tPA at 6 hours (6 of 8 rats [75%]). Reduction of mean arterial blood pressure from 122±3 to 99±2 mm Hg with hydralazine, given to SHR for 1 week before ischemia, significantly decreased the incidence of hemorrhage in 2 of 11 rats (18%). tPA reduced infarct volumes, but cotreatment with hydralazine did not result in further protection.

Conclusions—This study demonstrates that in this rat thromboembolic model of stroke, tPA-induced hemorrhage is dependent on blood pressure and that pharmacological reduction of hypertension during fibrinolysis can reduce the risk of hemorrhagic transformation.

Key Words: cerebral hemorrhage • fibrinolysis • hypertension • stroke • rats

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