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. 2013 Dec;2(4):379-88.
doi: 10.1177/2048872613504698. Epub 2013 Sep 5.

Patients with microvascular obstruction after primary percutaneous coronary intervention show a gp91phox (NOX2) mediated persistent oxidative stress after reperfusion

Giampaolo Niccoli  1 , Andrea Celestini, Camilla Calvieri, Nicola Cosentino, Elena Falcioni, Roberto Carnevale, Cristina Nocella, Francesco Fracassi, Marco Roberto, Roberta P Antonazzo, Pasquale Pignatelli, Filippo Crea, Francesco Violi
Affiliations

Patients with microvascular obstruction after primary percutaneous coronary intervention show a gp91phox (NOX2) mediated persistent oxidative stress after reperfusion

Giampaolo Niccoli et al. Eur Heart J Acute Cardiovasc Care. 2013 Dec.

Abstract

Background: Persistent oxidative stress may play a key role in microvascular obstruction (MVO). We aimed at assessing the role of platelet gp91phox (NOX2), the catalytic subunit of NADPH oxidase in MVO.

Methods: We enrolled 40 patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention within 12 h from symptoms onset, either with angiographic MVO (n=20) or good angiographic myocardial reperfusion (MR) (n=20). Angiographic MVO was defined as a final thrombolysis in myocardial infarction (TIMI) flow ≤2 or TIMI flow of 3 with myocardial blush grade <2. NOX2 and isoprostanes (8-iso-PGF2α) levels, as assessed by enzyme-linked immunoadsorbent assay (ELISA) or by an enzyme immunoassays, respectively, were measured on admission, at 24 h and pre-discharge.

Results: NOX2 levels increased from baseline to pre-discharge in patients with angiographic MVO (20.25 (15-24.75) pg/ml vs 25.50 (17-29.25) pg/ml, p=0.02), but not in MR patients (p=0.45), with a significant interaction between baseline and pre-discharge levels among the two groups (p=0.04). The levels of 8-iso-PGF2α showed a trend to increase from baseline to pre-discharge in angiographic MVO patients (295 (183.50-389.25) pmol/l vs 322 (206-370) pmol/l, p=0.06), but not in patients with MR (p=0.56), with a trend for interaction between baseline and pre-discharge levels among the two groups (p=0.09).

Conclusion: Patients with MVO, but not those with myocardial reperfusion, have a sustained increase of NOX2 and 8-iso-PGF2α. Therapies targeting NOX2 or high dosage antioxidants should be tested for MVO prevention and treatment.

Keywords: ST-elevation myocardial infarction; microvascular obstruction; oxidative stress; primary percutaneous coronary intervention.

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Conflict of interest statement

Conflict of interest: The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
(a) Time profiles of gp91phox (NOX2) levels according to angiographic patterns of myocardial reperfusion (angiographic myocardial reperfusion vs angiographic microvascular obstruction (MVO)) before primary percutaneous coronary intervention (PPCI), 24 hours after PPCI and at pre-discharge. (b)Time profiles of 8-iso-PGF2α levels according to angiographic patterns of myocardial reperfusion (angiographic myocardial reperfusion vs angiographic MVO) before PPCI, 24 h after PPCI and at pre-discharge. Data are given as median and ranges, • indicates angiographic myocardial reperfusion, ■ indicates angiographic MVO.
Figure 2.
Figure 2.
(a)Time profiles of gp91phox (NOX2) levels according to angiographic patterns of myocardial reperfusion (electrocardiogram (ECG) myocardial reperfusion vs ECG microvascular obstruction (MVO)) before primary percutaneous coronary intervention (PPCI), 24 h after PPCI and at pre-discharge. (b)Time profiles of 8-iso-PGF2α levels according to angiographic patterns of myocardial reperfusion (ECG myocardial reperfusion vs ECG MVO) before PPCI, 24 h after PPCI and at pre-discharge. Data are given as median and ranges, • indicates electrocardiographic myocardial reperfusion, ■ indicates electrocardiographic MVO.
See this image and copyright information in PMC

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