BACKGROUND AND PURPOSE: 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.
BACKGROUND AND PURPOSE: 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 hypertensiverats (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 ratthromboembolic 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: Yince Loh; D Kim; Z-S Shi; S Tateshima; P M Vespa; N R Gonzalez; S Starkman; J L Saver; R Jahan; D S Liebeskind; G R Duckwiler; F Viñuela Journal: AJNR Am J Neuroradiol Date: 2010-04-15 Impact factor: 3.825
Authors: Toshihiko Kuroiwa; Guohua Xi; Ya Hua; Tavarekere N Nagaraja; Joseph D Fenstermacher; Richard F Keep Journal: Stroke Date: 2008-11-26 Impact factor: 7.914
Authors: Rami Abu Fanne; Taher Nassar; Sergei Yarovoi; Anwar Rayan; Itschak Lamensdorf; Michael Karakoveski; Polianski Vadim; Mahmud Jammal; Douglas B Cines; Abd Al-Roof Higazi Journal: Neuropharmacology Date: 2010-01-06 Impact factor: 5.250