Effects of intra-arterial urokinase on a non-human primate thromboembolic stroke model

J Pharmacol Sci. 2006 Apr;100(4):278-84. doi: 10.1254/jphs.fp0050872. Epub 2006 Mar 25.

Abstract

One of the most important prognostic factors in the thrombolytic treatment of acute ischemic stroke is to re-canalize. The purpose of this study was to evaluate the effectiveness and safety of urokinase in a primate thromboembolic stroke model. Thromboembolic stroke was accomplished via occlusion of the middle cerebral artery (MCA) obtained by injecting an autologous blood clot into the left internal carotid artery in 21 male cynomolgus monkeys. Animals were randomly assigned to the following treatment groups: Group 1: vehicle (saline), Group 2: urokinase (40,000 IU), Group 3: urokinase (120,000 IU,) over 2 or 6 h via intra-internal carotid catheter starting 1 h after embolization, respectively. In the urokinase-treated groups, neurologic deficits were improved in consciousness and skeletal muscle coordination, but not sensory and motor systems. The infarction size in Group 2 (11.9 +/- 3.9% of the hemisphere) and 3 (7.6 +/- 2.5%) were significantly smaller than that (24.7 +/- 3.5%) in Group 1. However, 2 of 5 animals in Group 3 died. In conclusion, urokinase improved neurologic deficits and reduced cerebral infarction on thromboembolic stroke in the cynomolgus monkey.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drug Administration Schedule
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / therapeutic use*
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / pathology
  • Infusions, Intra-Arterial
  • Macaca fascicularis
  • Male
  • Nervous System Diseases / etiology
  • Nervous System Diseases / prevention & control*
  • Thromboembolism / complications
  • Thromboembolism / drug therapy*
  • Thromboembolism / pathology
  • Thrombolytic Therapy*
  • Urokinase-Type Plasminogen Activator / administration & dosage
  • Urokinase-Type Plasminogen Activator / therapeutic use*

Substances

  • Fibrinolytic Agents
  • Urokinase-Type Plasminogen Activator