Low-dose sodium nitrite attenuates myocardial ischemia and vascular ischemia-reperfusion injury in human models
Open accessAbstract
Objectives The aim of this study was to assess the potential benefits of inorganic nitrite in 2 clinical models: stress-induced myocardial ischemia and whole-arm ischemia-reperfusion.Background Inorganic nitrite, traditionally considered a relatively inert metabolite of nitric oxide, may exert vasomodulatory and vasoprotective effects. Despite promising results from animal models, few have shown effectiveness in human model systems, and none have fully translated to the clinical setting.Methods In 10 patients with inducible myocardial ischemia, saline and low-dose sodium nitrite (NaNO₂) (1.5 μmol/min for 20 min) were administered in a double-blind fashion during dobutamine stress echocardiography, at separate visits and in a random order; long-axis myocardial function was quantified by peak systolic velocity (Vs) and strain rate (SR) responses. In 19 healthy subjects, flow-mediated dilation was assessed before and after whole-arm ischemia-reperfusion; nitrite was given before ischemia or during reperfusion.Results Comparing saline and nitrite infusions, Vs and SR at peak dobutamine increased in regions exhibiting ischemia (Vs from 9.5 ± 0.5 cm/s to 12.4 ± 0.6 cm/s, SR from -2.0 ± 0.2 s(-1) to -2.8 ± 0.3 s(-1)), whereas they did not change in normally functioning regions (Vs from 12.6 ± 0.4 cm/s to 12.6 ± 0.6 cm/s, SR from -2.6 ± 0.3 s(-1) to -2.3 ± 0.1 s(-1)) (p < 0.001, analysis of variance). With NaNO2, the increment of Vs (normalized for increase in heart rate) increased only in poorly functioning myocardial regions (+122%, p < 0.001). Peak flow-mediated dilation decreased by 43% after ischemia-reperfusion when subjects received only saline (6.8 ± 0.7% vs. 3.9 ± 0.7%, p < 0.01); administration of NaNO2 before ischemia prevented this decrease in flow-mediated dilation (5.9 ± 0.7% vs. 5.2 ± 0.5%, p = NS), whereas administration during reperfusion did not.Conclusions Low-dose NaNO₂ improves functional responses in ischemic myocardium but has no effect on normal regions. Low-dose NaNO₂ protects against vascular ischemia-reperfusion injury only when it is given before the onset of ischemia.
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Nitrate supplementation prevents or limits ischemia-reperfusion injury and endothelial dysfunction in both animal and human models of ischemia-reperfusion.
“while nitrate supplementation prevents or limits ischemia-reperfusion injury and endothelial dysfunction in both animal[98,120–124] and human[97,125] models of ischemia-reperfusion.”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [125]
In adults with inducible myocardial ischemia, venous infusion of sodium nitrite improves functional cardiac responses during dobutamine stress echocardiography, suggesting nitrite acts as a coronary vasodilator.
“In adults with inducible myocardial ischemia, venous infusion of sodium nitrite improves functional cardiac responses during dobutamine stress echocardiography, suggesting that nitrite acts as a coronary vasodilator (76).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [76]
In healthy young humans, acute venous infusion of sodium nitrite increases resistance to temporary ischemia/reperfusion injury in the peripheral circulation.
“in healthy young humans, acute venous infusion of sodium nitrite increases resistance to temporary (reversible) I/R injury in the peripheral circulation, as assessed noninvasively by measuring the decrease in brachial artery flow-mediated dilation from normal baseline levels following cuff inflation-induced blood flow occlusion to the forearm (76).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [76]
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References 46 · Cited by 69
Research works printed but not linked: 3
- Reichart E, Mitchell S. On the physiological action of potassium nitrite. Am J Med Sci 1880;154:158-80.
- Collier W. A case of angina pectoris treated with nitrite of sodium; remarks. Lancet 1883;122:901.
- Sicari R, Nihoyannopoulos P, Evangelista A, et al. Stress echocardi- ography expert consensus statementdexecutive summary. Eur Heart J 2009;30:278-89.
- Authors
- Ingram, T. E., Fraser, A. G., Bleasdale, R. A., Ellins, E. A., Margulescu, A. D., Halcox, J. P., & James, P. E.
- Affiliations
- Cardiff University (GB)
- Royal Glamorgan Hospital (GB)
- Corresponding author
- James, Philip E.
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 61
- Issue
- 25
- Pages
- 2534-2541
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W1964555955
- Cited by
- 69
- References
- 46
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 5 · 2020: 2 · 2019: 7 · 2018: 7 · 2017: 9 · 2016: 7 · 2015: 8 · 2014: 7 · 2013: 1
- FWCI
- 5.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- British Heart Foundation (FS/06/088)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Keywords
- sodium nitrite, inorganic nitrite, myocardial ischemia, ischemia-reperfusion injury, flow-mediated dilation, vascular protection, dobutamine stress echocardiography, strain rate imaging, peak systolic velocity, nitric oxide metabolites, vasomodulation
- MeSH terms
- Adult, Aged, Cardiotonic Agents, Double-Blind Method, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Sodium Nitrite, Myocardial Reperfusion Injury, Myocardial Ischemia, Young Adult
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