title: Unfractionated heparin: multitargeted therapy for delayed neurological deficits induced by subarachnoid hemorrhage.
abstract: Aneurysmal subarachnoid hemorrhage (SAH) is associated with numerous "delayed neurological deficits" (DNDs) that have been attributed to multiple pathophysiological mechanisms, including ischemia, microthrombosis, free radical damage, inflammation, and vascular remodeling. To date, effective prophylactic therapy for SAH-induced DNDs has been elusive, due perhaps to the multiplicity of mechanisms involved that render typical, single-agent therapy seemingly futile. We hypothesized that heparin, which has multiple underappreciated salutary effects, might be useful as a multitargeted prophylactic agent against SAH-induced DNDs. We performed a comprehensive review of the literature to evaluate the potential utility of heparin in targeting the multiple pathophysiological mechanisms that have been identified as contributing to SAH-induced DNDs. Our literature review revealed that unfractionated heparin can potentially antagonize essentially all of the pathophysiological mechanisms known to be activated following SAH. Heparin binds >100 proteins, including plasma proteins, proteins released from platelets, cytokines, and chemokines. Also, heparin complexes with oxyhemoglobin, blocks the activity of free radicals including reactive oxygen species, antagonizes endothelin-mediated vasoconstriction, smooth muscle depolarization, and inflammatory, growth and fibrogenic responses. Our review suggests that the use of prophylactic heparin following SAH may warrant formal study.
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, 22 S. Greene St., Suite S12D, Baltimore, MD 21201-1595, USA. msimard@smail.umaryland.edu
authors.forename: J Marc
authors.initials: JM
authors.lastname: Simard
authors.forename: David
authors.initials: D
authors.lastname: Schreibman
authors.forename: E Francois
authors.initials: EF
authors.lastname: Aldrich
authors.forename: Bernadette
authors.initials: B
authors.lastname: Stallmeyer
authors.forename: Brian
authors.initials: B
authors.lastname: Le
authors.forename: Robert F
authors.initials: RF
authors.lastname: James
authors.forename: Narlin
authors.initials: N
authors.lastname: Beaty
mesh_terms: D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000503:physiopathology; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
chemical_list: D007004:Hypoglycemic Agents; D006493:Heparin
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