Jones Daniel A, Khambata Rayomand S, Andiapen Mervyn, Rathod Krishnaraj S, Mathur Anthony, Ahluwalia Amrita
Barts NIHR Cardiovascular Biomedical Research Unit, William Harvey Research Institute, Barts & The London Medical School, Queen Mary University of London, London, UK.
Department of Cardiology, Barts Health NHS Trust, London, UK.
Heart. 2017 Apr;103(7):508-516. doi: 10.1136/heartjnl-2016-309748. Epub 2016 Sep 28.
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.
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.
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.
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.
NCT01584453.
近期研究表明，冠状动脉内注射亚硝酸盐可减小急性心肌梗死（AMI）患者接受直接经皮冠状动脉介入治疗（PPCI）后的心肌梗死面积，但其确切机制尚不清楚。我们通过评估血浆中特定促炎介质、趋化因子和黏附分子的水平以及循环细胞亚型，探索亚硝酸盐对再灌注诱导炎症的影响，将其作为NITRITE-AMI队列研究的探索性终点。
在接受冠状动脉内注射亚硝酸钠（N = 40）或安慰剂（N = 40）的AMI患者接受PPCI期间，检测其外周血白细胞亚群、细胞黏附分子、高敏C反应蛋白（hs-CRP）、单核细胞和中性粒细胞趋化因子CCL2和CXCL1、CXCL5水平。在PPCI后3年记录主要不良心脏事件。
在接受安慰剂治疗的患者中，再灌注后循环中性粒细胞总数和hs-CRP水平升高，随后随时间下降；在接受亚硝酸盐治疗的患者中，与安慰剂相比，这些变化在PPCI后6个月内受到抑制（p<0.01）。这种效应与中性粒细胞CD11b表达降低、血浆CXCL1、CXCL5和CCL2水平降低有关（p<0.05）。治疗组之间在其他任何检测的白细胞群体数量（单核细胞和淋巴细胞）或这些细胞表达的活化标志物方面没有差异。这些效应与微血管阻塞和梗死面积的减少有关。
ST段抬高型心肌梗死患者在PPCI后中性粒细胞数量和活化程度的显著降低与亚硝酸盐治疗有关，我们认为这一效应可能至少部分是亚硝酸盐对梗死面积产生有益影响的基础。
NCT01584453。
