Abstract 17991: Markers of Acute Neutrophil Activation are Significantly Correlated with Elevated Plasma Human Neutrophil Elastase Levels at The Culprit Coronary Lesion Following Acute Occlusive Plaque Disruption an Acute ST Elevation Myocardial Infarction
Neutrophil proteases such as human neutrophil elastase (HNE) have been shown in animal models to enhance continuing fibrin generation in vascular thrombosis in the absence of infection. We hypothesized in acute STEMI patients undergoing primary PCI that acute neutrophil activation with elevation of plasma HNE occurs at the culprit coronary lesion following acute occlusive plaque disruption.
Methods: Eighty one patients with acute STEMI presenting < 6 hours had sampling performed from femoral artery (FA), aorta (Ao), culprit coronary lesion (CA) and coronary sinus (CS), pre and post PCI. Plasma HNE was measured using ELISA, and in sub group (n=40) acute flow cytometry was performed on whole blood for markers of acute neutrophil activation. Data = median + interquartile range
Results: Plasma HNE levels were higher in STEMI at all sites (p<0.001) compared to elective PCI controls (n = 11). In STEMI group, plasma HNE levels were higher at CA pre PCI (n = 74, 39 ng/ml, 26-66) versus all other sites (FA: n = 72, 27 ng/ml, 19-41) (Ao: n = 75, 27 ng/ml, 19-41) (CS: n = 46, 27 ng/ml, 20-51)( all p<0.001), with no difference between sampling sites in control group. In STEMI patients pre PCI, although plasma HNE was negatively correlated with neutrophil MPO content at all sites (all p < 0.05), plasma HNE only correlated with neutrophil forward scatter (r = -0.5, p < 0.01) and neutrophil CD11b (r = 0.4, p = 0.01) at CA. Between 2 and 4 hours from onset of symptoms to PCI, HNE correlated with neutrophil MPO content pre PCI only at Ao (r = -0.6, p < 0.01) and CA (r = -0.5, p < 0.05), and with neutrophil CD11b only at CA (r = 0.5, p = 0.017), but there were no correlations prior to 2 hours. Plasma HNE levels at CA pre PCI in STEMI negatively correlated with 6 month LV ejection fraction (r = -0.6, p < 0.05), but no correlation was seen in STEMI subgroup receiving aspiration of thrombus at culprit lesion prior to stenting.
Conclusion: In STEMI patients pre PCI, more intense neutrophil activation is associated with elevation of plasma HNE at culprit coronary lesion pre PCI 2-4 hours following acute occlusive plaque disruption. Our preliminary results imply a potential role for endogenous elastase inhibitors to reduce intra-coronary inflammation and prevent propagation of occlusive thrombosis in acute STEMI.
- © 2012 by American Heart Association, Inc.