Intracoronary nitrite suppresses the inflammatory response following primary percutaneous coronary intervention

Abstract

NCT01584453.

The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway

“…Accordingly, data in humans have emerged from a phase 2 study suggesting that nitrite, and presumably nitrite-derived •NO, exerts anti-inflammatory effects when given during primary PCI for AMI (Jones et al, 2015a). In these patients, we demonstrated important reductions in neutrophil numbers and activation post-primary PCI (Jones et al, 2017). In the placebo-treated patients, we observed increases in the total circulating neutrophil numbers and levels of high-sensitivity C-reactive protein postreperfusion, which then decreased over time.…”

“…Importantly, there were no differences in the number of any other leukocyte population measured (monocytes and lymphocytes) or activation markers expressed by these cells between the Nitrate-Nitrite-Nitric Oxide Pathway treatment groups. In addition, these effects on inflammatory markers were associated with a reduction in both microvascular obstruction and infarct size, suggesting important effects of nitrite on neutrophil activation and recruitment (Jones et al, 2017). Further study is needed to examine these effects.…”

Sodium Nitrite–Mediated Cardioprotection in Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: A Cost-Effectiveness Analysis

“…Full details of the trial protocol and primary and secondary outcomes have been published. 1 –3 All participants gave written informed consent before being included in the study After coronary angiography, patients were randomized (1:1) to a high-dose bolus injection of intracoronary sodium nitrite (1.8 μmol in 10 mL of 0.9% NaCl) or placebo (10 mL of 0.9% NaCl) administered via an over-the-wire balloon catheter just prior to balloon inflation. All study personnel were blind to treatment allocation until the study and all analyses were completed.…”

“…In a recent phase II clinical trial, sodium nitrite given intracoronary at the time of primary PCI was associated with significant reductions in major adverse cardiac events (MACEs) during 3 years of follow-up (5.2% vs 25.0%, P = .013). 1,2 The extent of economic benefit associated with such MACE reductions is, as yet, unassessed. Therefore, we aimed to evaluate the cost–utility of sodium nitrite as an adjunctive therapy administered prior to primary PCI in patients with ST-segment elevation myocardial infarction (STEMI).…”

Cell biological mechanisms in regulation of the post-infarction inflammatory response

“…In addition to IL-1, several additional inflammatory targets have been suggested in patients with myocardial infarction. In human patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction, intracoronary nitrite treatment decreased inflammatory activation of leukocytes; these effects were associated with attenuated microvascular obstruction and with a reduction in infarct size [73]. IL-6 inhibition through administration of the IL-6 receptor antagonist tocilizumab attenuated the systemic inflammatory response and reduced cardiomyocyte injury in patients with non-STEMI undergoing PCI [74].…”