Sodium nitrite promotes regional blood flow in patients with sickle cell disease: A phase I/II study

A. Kyle Mack, Vicki R. McGowan, Carole K. Tremonti, Diana Ackah, Christopher Barnett, Roberto F. MacHado, Mark T. Gladwin, Gregory J. Kato

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

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 μmol/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.

Original languageEnglish (US)
Pages (from-to)971-978
Number of pages8
JournalBritish journal of haematology
Volume142
Issue number6
DOIs
StatePublished - Sep 1 2008
Externally publishedYes

Keywords

  • Blood flow
  • Nitrite
  • Nitroprusside
  • Sickle cell
  • Vasodilation

ASJC Scopus subject areas

  • Hematology

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