title: Hemorrhagic transformation after fibrinolysis with tissue plasminogen activator: evaluation of role of hypertension with rat thromboembolic stroke model.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Tejima
authors.forename: Y
authors.initials: Y
authors.lastname: Katayama
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Kano
authors.forename: E H
authors.initials: EH
authors.lastname: Lo
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006830:Hydralazine / Q000008:administration & dosage; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy; D015994:Incidence; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology; D020767:Intracranial Thrombosis / Q000150:complications* / Q000188:drug therapy; D017078:Laser-Doppler Flowmetry; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D015912:Thrombolytic Therapy / Q000009:adverse effects; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D006830:Hydralazine; D010959:Tissue Plasminogen Activator