Stroke. 48(Suppl_1):ATP92, FEB 2017
Issn Print: 0039-2499
Publication Date: 2017/02/01
Abstract TP92: Continuous Glyburide Infusion Prevents Hemorrhagic Transformation After Cerebral Infarction in a Rodent Reperfusion Model
Cristina Sastre;Takahiro Igarashi;Søren Larsen;Zoe Wolcott;Ann-Christin Ostwaldt;Phillip Sun;William Kimberly;
+ Author Information
1Cntr for Human Genetic Rsch and Div of Neurocritical Care and Emergency Neurology, Massachusetts General Hosp, Boston, MA2Athinoula A. Martinos Cntr for Biomedical Imaging and CHGR, Massachusetts General Hosp, Boston, MA3Athinoula A. Martinos Cntr for Biomedical Imaging, Massachusetts General Hosp, Boston, MA
Abstract
Introduction: Hemorrhagic transformation (HT) is an uncommon but adverse complication after a stroke that can cause secondary injury. We sought to determine whether glyburide can reduce HT in an ischemia/reperfusion model of stroke.Materials and Methods: We used a transient filament occlusion of the middle cerebral artery (tMCAo), with three hours of cerebral ischemia. Glyburide (n=10) was administered as an intravenous bolus followed by a subcutaneous continuous infusion using an osmotic pump to deliver a dose of 39.5 ug/day. Control animals (n=10) were administered dimethyl sulfoxide vehicle. At 48 hours, infarct size, brain edema and HT were analyzed. HT was quantified using three methods, 1) a categorical designation based on European Cooperative Acute Stroke Study (ECASS) criteria, 2) densitometry of color images and 3) direct measurement of the hemoglobin concentration using spectrophotometry.Results: Compared to vehicle control, continuous glyburide treatment improved neurological outcome (7.6±1.0 vs. 6.0±0.9, P<0.01), reduced infarct volume (323±42 vs. 484±60mm3, P<0.01), swelling volume (10±4 vs. 28±7%, P<0.01) and water content (84±1 vs. 85±1%, P<0.05). Glyburide administration also reduced HT based on ECASS categories, densitometry on color images (0.9±0.1 vs. 1.1±0.1, P<0.01) and quantitative evaluation of hemoglobin (2.7±1.5 vs. 5.1±2.6uL, P<0.05).Conclusion: In a prolonged ischemia/reperfusion model, glyburide reduced the amount of hemorrhagic transformation. Clinical evaluation of glyburide in combination with mechanical thrombectomy may be warranted in patients.
