Acute hypertension, but not thrombolysis, increases the incidence and severity of hemorrhagic transformation following experimental stroke in rabbits

Exp Neurol. 1996 Sep;141(1):40-6. doi: 10.1006/exnr.1996.0137.


Hemorrhagic transformation (HT) is a poorly understood yet frequent complication of stroke. A transient increase in blood pressure (BP) occurs immediately after experimental embolization in rabbits and we evaluated the relationship between this acute hypertensive response and subsequent hemorrhagic transformation, as well as the attenuation of this hypertensive response with an anesthetic dose of halothane. We also examined embolism-induced HT during infusion of the thrombolytic agents tissue plasminogen activator and streptokinase. A blood clot embolus was injected into the internal carotid artery and flushed into the middle cerebral artery. In the first experiment, BP was monitored in anesthetized or unanesthetized rabbits for 20 min prior to and up to 1 h after embolization. In the second experiment, animals were embolized half-way through an infusion of tPA (3.0 mg/kg; 20% administered as an iv bolus, with the remainder infused over 30 min) or streptokinase (30,000 U/kg iv infused over 30 min). In unanesthetized animals, the HT score (number of brain sections displaying visible HT) was significantly correlated with the peak mean arterial pressure recorded at embolization (r = 0.60, n = 24, P < 0.01). No relationship was observed between BP and HT score in animals anesthetized with halothane. Although HT incidence and extent were significantly related to elevated BP in the unanesthetized animals, halothane administration actually increased HT incidence. Embolization during thrombolytic infusion did not increase the occurrence or severity of HT. These data suggest that acute hypertension, but not ongoing thrombolysis, is a significant risk factor for HT following cerebral embolization.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Administration, Inhalation
  • Animals
  • Cerebral Hemorrhage / etiology*
  • Cerebral Hemorrhage / physiopathology
  • Cerebrovascular Disorders / complications*
  • Fibrinolytic Agents / pharmacology*
  • Halothane / pharmacology
  • Hypertension / complications*
  • Incidence
  • Male
  • Rabbits
  • Streptokinase / pharmacology*
  • Tissue Plasminogen Activator / pharmacology*


  • Fibrinolytic Agents
  • Streptokinase
  • Tissue Plasminogen Activator
  • Halothane