Hemorrhagic transformation after fibrinolysis with tissue plasminogen activator: evaluation of role of hypertension with rat thromboembolic stroke model.
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.
Tejima
E
E
Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
Katayama
Y
Y
Suzuki
Y
Y
Kano
T
T
Lo
E H
EH
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
D006830:Hydralazine; D010959:Tissue Plasminogen Activator