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 Machado, Mark T. Gladwin, Gregory J. Kato

Research output: Contribution to journalArticle

48 Citations (Scopus)

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

Fingerprint

Sodium Nitrite
Regional Blood Flow
Sickle Cell Anemia
Nitrites
Brachial Artery
Nitric Oxide Donors
Nitric Oxide
Methemoglobinemia
omega-N-Methylarginine
Phase II Clinical Trials
Clinical Trials, Phase I
Plethysmography
Nitroprusside
Vasoconstriction
Reperfusion Injury
Vasodilator Agents
Forearm
Cell Adhesion
Hypotension
Biological Availability

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

Sodium nitrite promotes regional blood flow in patients with sickle cell disease : A phase I/II study. / Mack, A. Kyle; McGowan, Vicki R.; Tremonti, Carole K.; Ackah, Diana; Barnett, Christopher; Machado, Roberto; Gladwin, Mark T.; Kato, Gregory J.

In: British Journal of Haematology, Vol. 142, No. 6, 01.09.2008, p. 971-978.

Research output: Contribution to journalArticle

Mack, A. Kyle ; McGowan, Vicki R. ; Tremonti, Carole K. ; Ackah, Diana ; Barnett, Christopher ; Machado, Roberto ; Gladwin, Mark T. ; Kato, Gregory J. / Sodium nitrite promotes regional blood flow in patients with sickle cell disease : A phase I/II study. In: British Journal of Haematology. 2008 ; Vol. 142, No. 6. pp. 971-978.
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