Combination of a free radical scavenger and heparin reduces cerebral hemorrhage after heparin treatment in a rabbit middle cerebral artery occlusion model.

Abstract

BACKGROUND AND PURPOSE:

We sought to investigate the effects of EPC-K1, a free radical scavenger, on reducing heparin-produced cerebral hemorrhage in a rabbit model of middle cerebral artery (MCA) photothrombosis and to investigate whether the combination of EPC-K1 and heparin enhances neuroprotection from cerebral ischemic damage.

METHODS:

In the heparin-alone group (n=8), heparin was administered intravenously for 24 hours, starting from 3 hours after MCA occlusion. In the EPC-K1-alone group (n=8), EPC-K1 was administered as a bolus injection (10 mg/kg) twice at 3 and 6 hours after MCA occlusion. In the combination group (n=8), EPC-K1 and heparin both were administered as in the single-drug procedures. In the vehicle group (n=10), saline were infused for 24 hours.

RESULTS:

Heparin prolonged activated partial thromboplastin time by approximately 3 times that of control animals. In the heparin-treated animals, the hemorrhage size was significantly increased (P<0.0001) and neurological symptoms were significantly worse (P<0.01) than in control animals at 48 hours. The combination of EPC-K1 and heparin dramatically reduced heparin-produced cerebral hemorrhage (P<0.0001), with a significant reduction in infarct volume (reduction by 63.2% and 57.2% of heparin-alone and control animals, respectively, P<0.0001) and a significant improvement in neurological symptoms (P<0.01 versus heparin-alone and control animals, respectively).

CONCLUSIONS:

These data indicate that free radical formation may play a key role in intracerebral hemorrhage exacerbated by heparin treatment and that the combination of a free radical scavenger and heparin augmented neuroprotection from acute brain ischemia. The results of the present study may suggest a potential clinical approach for the treatment of acute stroke.

• Authors: B Q Zhao, Y Suzuki, K Kondo, Y Ikeda, K Umemura
• Journal: Stroke (Stroke) Vol. 32 Issue 9 Pg. 2157-63 (Sep 2001) ISSN: 1524-4628 [Electronic] United States
• PMID: 11546911 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Free Radical Scavengers
• Vitamin E
• potassium ascorbyl tocopheryl phosphate
• Heparin
• Ascorbic Acid

Topics

• Animals
• Ascorbic Acid (administration & dosage, analogs & derivatives)
• Blood Flow Velocity (drug effects)
• Body Temperature (drug effects)
• Cerebral Hemorrhage (etiology, pathology, prevention & control)
• Disease Models, Animal
• Drug Therapy, Combination
• Free Radical Scavengers (administration & dosage)
• Heparin (administration & dosage, adverse effects)
• Infarction, Middle Cerebral Artery (complications, drug therapy, pathology, physiopathology)
• Light Coagulation
• Middle Cerebral Artery (drug effects, physiopathology)
• Partial Thromboplastin Time
• Rabbits
• Reperfusion
• Treatment Outcome
• Vitamin E (administration & dosage, analogs & derivatives)