| Sodium nitrite promotes regional blood flow in patients with sickle cell disease: a phase I/II study. | |
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MedLine Citation:
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PMID: 18671702 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In addition to vaso-occlusion by sickled erythrocytes, the pathophysiology of sickle cell disease (SCD) is compounded by the diminished bioavailability of nitric oxide (NO), associated with vasoconstriction, endothelial activation and cell adhesion. We tested the ability of sodium nitrite, which can be converted to NO by deoxyhaemoglobin at acid pH and low oxygen tension, to improve blood flow in patients with SCD. In a phase I/II clinical trial, sodium nitroprusside, NG-monomethyl-L-arginine, and sodium nitrite were infused sequentially into the brachial artery in 14 patients at steady state. In a dose-dependent manner, sodium nitrite infusion rates of 0.4, 4 and 40 micromol/min into the brachial artery augmented mean venous plasma nitrite concentrations (P < 0.0001) and stimulated forearm blood flow up to 77 +/- 11% above baseline (P < 0.0001), measured by venous occlusion strain gauge plethysmography. This nitrite response was blunted significantly compared to controls without SCD, as previously seen with other NO donors. Sodium nitrite infusions were well tolerated without hypotension, clinically significant methaemoglobinaemia or other untoward events. The unique pharmacological properties of nitrite as a hypoxia-potentiated vasodilator and cytoprotective agent in the setting of ischaemia-reperfusion injury make this anion a plausible NO donor for future clinical trials in SCD. |
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Authors:
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A Kyle Mack; Vicki R McGowan Ii; Carole K Tremonti; Diana Ackah; Christopher Barnett; Roberto F Machado; Mark T Gladwin; Gregory J Kato |
Publication Detail:
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Type: Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Research Support, N.I.H., Intramural Date: 2008-07-11 |
Journal Detail:
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Title: British journal of haematology Volume: 142 ISSN: 1365-2141 ISO Abbreviation: Br. J. Haematol. Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-10-10 Completed Date: 2008-12-11 Revised Date: 2011-10-19 |
Medline Journal Info:
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Nlm Unique ID: 0372544 Medline TA: Br J Haematol Country: England |
Other Details:
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Languages: eng Pagination: 971-8 Citation Subset: IM |
Affiliation:
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Pulmonary and Vascular Medicine Branch, National Heart, Lung and Blood Institute; National Institutes of Health, Bethesda, MD, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Anemia, Sickle Cell / blood, drug therapy, physiopathology* Dose-Response Relationship, Drug Forearm / blood supply Humans Middle Aged Nitric Oxide Donors / diagnostic use Nitroprusside / diagnostic use Regional Blood Flow / drug effects Sodium Nitrite / adverse effects, blood, pharmacology*, therapeutic use Vasodilation / drug effects Vasodilator Agents / adverse effects, blood, pharmacology*, therapeutic use Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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Z01 CL008081-03/CL/CLC NIH HHS; ZIA HL006024-02/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Nitric Oxide Donors; 0/Vasodilator Agents; 15078-28-1/Nitroprusside; 7632-00-0/Sodium Nitrite |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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