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

Eur Heart J Acute Cardiovasc Care. 2013 Dec;2(4):379-88. doi: 10.1177/2048872613504698. Epub 2013 Sep 5.

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.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Coronary Angiography
  • Coronary Circulation*
  • Coronary Restenosis / blood*
  • Coronary Restenosis / diagnostic imaging
  • Coronary Restenosis / etiology
  • Electrocardiography
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Membrane Glycoproteins / blood*
  • Microcirculation*
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / surgery*
  • NADPH Oxidase 2
  • NADPH Oxidases / blood*
  • Oxidative Stress*
  • Percutaneous Coronary Intervention / adverse effects*
  • Postoperative Complications
  • Prognosis
  • Retrospective Studies

Substances

  • Biomarkers
  • Membrane Glycoproteins
  • CYBB protein, human
  • NADPH Oxidase 2
  • NADPH Oxidases