title: Effects of U74006F on multifocal cerebral blood flow and metabolism after cardiac arrest in dogs.
abstract: Lipid peroxidation reactions during reperfusion after cardiac arrest may contribute to postischemic cerebral hypoperfusion, which in turn can contribute to permanent neurological dysfunction. We designed this study to determine whether the aminosteroid U74006F, a putative inhibitor of lipid peroxidation, mitigates cerebral multifocal hypoperfusion after cardiac arrest. We used our established dog model of ventricular fibrillation cardiac arrest (no blood flow) of 12.5 minutes, reperfusion by cardiopulmonary bypass of less than or equal to 5 minutes, and control of extracerebral variables during 4 hours postarrest. Cerebral blood flow was monitored by the stable xenon computed tomography method. Changes in cerebral oxygen consumption were obtained from mean blood flow values of coronal slices and the cerebral arteriovenous (sagittal sinus) oxygen content difference. A treatment group (n = 5) received U74006F starting with reperfusion (1.5 mg/kg i.a. plus 1.5 mg/kg i.v.) and three additional (graded) doses over 4 hours (total dose 4.5, 7.5, or 14.5 mg/kg). The U74006F-treated group showed the same postarrest transient hyperemia and protracted hypoperfusion in terms of global (computed tomography slice), regional, and local (multifocal) cerebral blood flow values and the same global cerebral oxygen consumption pattern as a concurrent control group (n = 5). At 1-4 hours postarrest, in both groups there was mismatching of global cerebral oxygen consumption, which reached baseline values, in relation to global cerebral blood flow and oxygen delivery, which remained at 50% of baseline. We conclude that treatment with U74006F after prolonged cardiac arrest causes no deleterious side effects and does not seem to alter multifocal postarrest cerebral blood flow and oxygen consumption.
authors.affiliation: International Resuscitation Research Center, University of Pittsburgh, Pa 15260.
authors.forename: F
authors.initials: F
authors.lastname: Sterz
authors.forename: P
authors.initials: P
authors.lastname: Safar
authors.forename: D W
authors.initials: DW
authors.lastname: Johnson
authors.forename: K
authors.initials: K
authors.lastname: Oku
authors.forename: S A
authors.initials: SA
authors.lastname: Tisherman
mesh_terms: D000818:Animals; D001158:Arteries; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003392:Cranial Sinuses; D004285:Dogs; D006323:Heart Arrest / Q000378:metabolism*; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors; D008297:Male; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D011281:Pregnatrienes / Q000494:pharmacology*; D014057:Tomography, X-Ray Computed; D014978:Xenon
chemical_list: D008054:Lipid Peroxides; D011281:Pregnatrienes; D014978:Xenon; D010100:Oxygen; C053355:tirilazad