Related Experiment Video
Updated: Mar 14, 2026
Acetylcholine Re-Challenge After Intracoronary Nitroglycerine Administration
Published on: April 4, 2022
Intracoronary nitrite suppresses the inflammatory response following primary percutaneous coronary intervention
Daniel A Jones1,2, Rayomand S Khambata1, Mervyn Andiapen2
1Barts NIHR Cardiovascular Biomedical Research Unit, William Harvey Research Institute, Barts & The London Medical School, Queen Mary University of London, London, UK.
Insights
Intracoronary nitrite treatment reduced inflammation and infarct size in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PPCI). This suggests nitrite may be a beneficial therapy for AMI by suppressing neutrophil activation.
Area of Science:
- Cardiology
- Immunology
- Pharmacology
Background:
- Intracoronary nitrite has shown potential in reducing myocardial infarct size after primary percutaneous coronary intervention (PPCI) for acute myocardial infarction (AMI).
- The precise mechanisms by which nitrite exerts its beneficial effects, particularly concerning reperfusion-induced inflammation, remain incompletely understood.
Purpose of the Study:
- To investigate the impact of intracoronary sodium nitrite on reperfusion-induced inflammatory responses in patients with AMI undergoing PPCI.
- To assess the effects of nitrite on pro-inflammatory mediators, chemokines, and adhesion molecules in plasma and circulating immune cells.
Main Methods:
- A randomized controlled trial (NITRITE-AMI cohort) involving 80 patients with AMI undergoing PPCI.
- Patients received either intracoronary sodium nitrite (N=40) or a placebo (N=40).
- Measurements included peripheral blood leukocyte subsets, cell adhesion molecules, high-sensitivity C-reactive protein (hs-CRP), and specific chemokines (CCL2, CXCL1, CXCL5) at various time points. Major adverse cardiac events were tracked for 3 years.
Main Results:
- Nitrite treatment significantly suppressed the post-reperfusion increase in circulating neutrophil numbers and hs-CRP levels compared to placebo, up to 6 months post-PPCI.
- This suppression was associated with reduced expression of neutrophil CD11b and lower plasma levels of CXCL1, CXCL5, and CCL2.
- No significant differences were observed in other leukocyte populations or their activation markers between groups. These inflammatory changes correlated with reduced microvascular obstruction and infarct size.
Conclusions:
- Intracoronary nitrite administration effectively reduces neutrophil activation and associated inflammatory markers following PPCI in ST-elevated myocardial infarction patients.
- The observed anti-inflammatory effects of nitrite likely contribute significantly to its beneficial impact on reducing infarct size in AMI.
Objective:
Recent work suggests that intracoronary nitrite reduces myocardial infarct size following primary percutaneous coronary intervention (PPCI) for acute myocardial infarction (AMI), although the exact mechanisms are unclear. We explored the effects of nitrite on reperfusion-induced inflammation, by assessing the levels of specific pro-inflammatory mediators, chemokines and adhesion molecules in plasma and circulating cell subtypes as exploratory end points in the NITRITE-AMI cohort.
Methods:
Peripheral blood leucocyte subsets, cell adhesion molecules, high-sensitivity C reactive protein (hs-CRP), the monocyte and neutrophil chemoattractants CCL2 and CXCL1, CXCL5, respectively were measured in the blood of patients who received either intracoronary sodium nitrite (N=40) or placebo (N=40) during PPCI for AMI. Major adverse cardiac events were recorded at 3 years post-PPCI.
Results:
In the placebo-treated patients, total circulating neutrophil numbers and levels of hs-CRP were raised postreperfusion and then decreased over time; in nitrite-treated patients these changes were suppressed compared with placebo up to 6 months post-PPCI (p<0.01). This effect was associated with reduced expression of neutrophil CD11b, plasma CXCL1, CXCL5 and CCL2 levels (p<0.05). There were no differences in the number of other any other leucocyte population measured (monocytes and lymphocytes) or activation markers expressed by these cells between the treatment groups. These effects were associated with a reduction in both microvascular obstruction and infarct size.
Conclusions:
Important reductions in neutrophil numbers and activation post-PPCI in patients with ST elevated myocardial infarction were associated with nitrite treatment, an effect we propose likely underlies, at least in part, the beneficial effects of nitrite upon infarct size.
Trial Registration Number:
NCT01584453.
Related Concept Videos
01:28Acute Coronary Syndrome IV: Interprofessional Care
01:27Coronary Artery Disease V: Interprofessional Care
01:16Antianginal Drugs: Nitrates and β-Blockers
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow....
01:26Angina IV: Management
01:20Angina V: Nursing Management
01:26Acute Coronary Syndrome V: Nursing Management