title: Acute hypertension promotes hemorrhagic transformation in a rabbit embolic stroke model: effect of labetalol.
abstract: We examined the relationship between acute hypertension following cerebral embolization and subsequent hemorrhagic transformation (HT) in a rabbit embolic stroke model. We have shown previously that the likelihood and severity of hemorrhage were significantly correlated with the magnitude of an acute hypertensive response to embolization. It was not clear, however, whether hypertension actually caused hemorrhage or was merely a marker of more severe stroke. In the current studies, we attempted to clarify the relationship between acute hypertension and HT by either pharmacologically inducing or attenuating the brief hypertensive response to embolization in rabbits. Under halothane anesthesia, two catheters were implanted in the right carotid arteries of male New Zealand white rabbits, one oriented toward the heart and one toward the brain. The animals were allowed to awaken and were embolized using blood clot emboli injected into the middle cerebral artery. Blood pressure was monitored via the second carotid catheter. In the first experiment, hypertension was induced with angiotensin II, administered at the time of embolization or 1 h later. In the second experiment, we attempted to attenuate the hypertensive response using intravenous labetalol. The animals were sacrificed 18 h after embolization and the brains evaluated for hemorrhage. In the first experiment, administration of angiotensin II immediately after embolization did not increase the hypertensive response to embolization further than that spontaneously occurring, and no angiotensin II-related HT was observed. In contrast, an additional angiotensin-II-induced hypertensive episode 1 h after embolization significantly increased the number of 5-mm serial brain sections displaying HT, from 3.0 +/- .3 (mean +/- SE) in Controls to 5.4 +/- .8 in treated animals. In the second experiment, administration of labetalol (15 mg/kg) significantly reduced the number of brain sections with visible HT, from 3.2 +/- .5 in controls to 1.6 +/- .4 in treated animals. Acute hypertension during the first hour after cerebral embolization promotes HT in this rabbit embolic stroke model. Labetalol prevents blood pressure elevation and reduces the extent of HT in the same model.
authors.affiliation: Department of Pharmacy Practice, Wayne State University, Detroit, Michigan, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Fagan
authors.forename: M P
authors.initials: MP
authors.lastname: Bowes
authors.forename: P D
authors.initials: PD
authors.lastname: Lyden
authors.forename: J A
authors.initials: JA
authors.lastname: Zivin
mesh_terms: D000208:Acute Disease; D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000473:pathology; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology; D006973:Hypertension / Q000139:chemically induced / Q000150:complications*; D002542:Intracranial Embolism and Thrombosis / Q000150:complications*; D007741:Labetalol / Q000627:therapeutic use*; D008297:Male; D011817:Rabbits
chemical_list: D000959:Antihypertensive Agents; D000804:Angiotensin II; D007741:Labetalol