Neutrophils are primary source of O 2 radicals during reperfusion after prolonged myocardial ischemia

Carlo Duilio, Giuseppe Ambrosio, Periannan Kuppusamy, Anthony Dipaula, Lewis Becker, Jay L. Zweier

Research output: Contribution to journalArticle

Abstract

Although many studies document oxygen radical formation during ischemia-reperfusion, few address the sources of radicals in vivo or examine radical generation in the context of prolonged ischemia. In particular, the contribution of activated neutrophils remains unclear. To investigate this issue, we developed a methodology to detect radicals without interfering with blood-borne mechanisms of radical generation. Dogs underwent aorta and coronary sinus catheterization. No chemicals were infused; instead, blood was drawn into syringes prefilled with a spin trap and analyzed by electron paramagnetic resonance spectroscopy. After 90 rain of coronary artery occlusion, transcardiac concentration of oxygen radicals rose severalfold 10 min after reflow and remained significantly elevated for at least 1 h. Radicals were mostly derived from neutrophils, as shown by marked reduction after the administration of 1) neutrophil NADPH oxidase inhibitors and 2) a monoclonal antibody (R15.7) against neutrophil CD18 adhesion molecule. Reduction of radical generation by R15.7 was also associated with a significantly smaller infarct size and no-reflow areas. Thus our data demonstrate that neutrophils are a major source of oxidants in hearts reperfused in vivo after prolonged ischemia and that antineutrophil interventions can effectively prevent the increase in oxygen radical concentration during reperfusion.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number6 49-6
StatePublished - 2001

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Reperfusion
Myocardial Ischemia
Neutrophils
Reactive Oxygen Species
Ischemia
Rain
Coronary Sinus
Coronary Occlusion
Syringes
Electron Spin Resonance Spectroscopy
Oxidants
Catheterization
Aorta
Spectrum Analysis
Coronary Vessels
Monoclonal Antibodies
Dogs

Keywords

  • Electron paramagnetic resonance
  • Myocardial infarction
  • Reperfusion injury

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Neutrophils are primary source of O 2 radicals during reperfusion after prolonged myocardial ischemia. / Duilio, Carlo; Ambrosio, Giuseppe; Kuppusamy, Periannan; Dipaula, Anthony; Becker, Lewis; Zweier, Jay L.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 280, No. 6 49-6, 2001.

Research output: Contribution to journalArticle

Duilio, Carlo ; Ambrosio, Giuseppe ; Kuppusamy, Periannan ; Dipaula, Anthony ; Becker, Lewis ; Zweier, Jay L. / Neutrophils are primary source of O 2 radicals during reperfusion after prolonged myocardial ischemia. In: American Journal of Physiology - Heart and Circulatory Physiology. 2001 ; Vol. 280, No. 6 49-6.
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AU - Zweier, Jay L.

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