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.
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Authors | J Marc Simard, David Schreibman, E Francois Aldrich, Bernadette Stallmeyer, Brian Le, Robert F James, Narlin Beaty |
Journal | Neurocritical care
(Neurocrit Care)
Vol. 13
Issue 3
Pg. 439-49
(Dec 2010)
ISSN: 1556-0961 [Electronic] United States |
PMID | 20809188
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review)
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Chemical References |
- Hypoglycemic Agents
- Heparin
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Topics |
- Brain Ischemia
(drug therapy, etiology, physiopathology)
- Heparin
(therapeutic use)
- Humans
- Hypoglycemic Agents
(therapeutic use)
- Subarachnoid Hemorrhage
(complications, physiopathology)
- Vasospasm, Intracranial
(drug therapy, etiology, physiopathology)
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