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We hypothesized that NETs would be induced during myocardial ischemia-reperfusion (I\/R), and NET-mediated microthrombosis may contribute to myocardial \u201cno-reflow\u201d. Male Wistar rats were randomly divided into I\/R control, DNase (DNase I, 20 \u03bcg\/rat), recombinant tissue-type plasminogen activator (rt-PA, 420 \u03bcg\/rat), DNase + rt-PA, and sham control groups after 45-min myocardial ischemia. In situ NET formation, the anatomic \u201cno re-flow\u201d area, and infarct size were evaluated immediately after 3 h of reperfusion. Long-term left ventricular (LV) functional and histological analyses were performed 45 days after operation. Compared with the I\/R controls, the DNase + rt-PA group exhibited reduced NET density [8.38 \u00b1 1.98 vs. 26.86 \u00b1 3.07 (per 200 \u00d7 field), P &lt; 0.001] and \u201cno-flow\u201d area (15.22 \u00b1 0.06 vs. 34.6 \u00b1 0.05%, P &lt; 0.05) in the ischemic region, as well as reduced infarct size (38.39 \u00b1 0.05 vs. 71.00 \u00b1 0.03%, P &lt; 0.001). Additionally, compared with the I\/R controls, DNase + rt-PA treatment significantly ameliorated I\/R injury-induced LV remodeling (LV ejection fraction: 64.22 \u00b1 3.37 vs. 33.81 \u00b1 2.98%, P &lt; 0.05; LV maximal slope of the LV systolic pressure increment: 3,785 \u00b1 216 vs. 2,596 \u00b1 299 mmHg\/s, P &lt; 0.05). The beneficial effect was not observed in rats treated with DNase I or rt-PA alone. Our study provides evidence for the existence of NETs in I\/R-challenged myocardium and confirms the long-term benefit of a novel DNase-based reperfusion strategy (DNase I + rt-PA), which might be a promising option for the treatment of myocardial I\/R injury and coronary no-reflow.<\/jats:p>","DOI":"10.1152\/ajpheart.00381.2014","type":"journal-article","created":{"date-parts":[[2014,12,20]],"date-time":"2014-12-20T02:04:39Z","timestamp":1419041079000},"page":"H500-H509","source":"Crossref","is-referenced-by-count":249,"title":["Neutrophil extracellular traps in ischemia-reperfusion injury-induced myocardial no-reflow: therapeutic potential of DNase-based reperfusion strategy"],"prefix":"10.1152","volume":"308","author":[{"given":"Lan","family":"Ge","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of the Chinese People's 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