Identification of Hydrogen Peroxide and Hydroxyl Radical as Mediators of LeukocyteInduced Myocardial Dysfunction

Limitation of Infarct Size with Neutrophil Inhibition and Depletion
  • Michael L. Hess
  • G. Thomas Rowe
  • Martin Caplan
  • Joseph L. Romson
  • Benedict Lucchesi
Part of the Advances in Myocardiology book series (ADMY)

Abstract

Neutrophil infiltration of the myocardium is an important component of such diverse diseasé entities as myocarditis, ischemia, and ischemia-reperfusion injury. We have hypothesized that activated neutrophils are capable of disrupting myocardial function via an oxygen free-radical mechanism. Human neutrophils activated with phorbol myristate acetate disrupted calcium transport by canine cardiac sarcoplasmic reticulum, and this process was inhibited by a combination of superoxide dismutase and catalase. In addition, the activated neutrophil system was also inhibited by the combination of cyclooxygenase inhibitors (ibuprofen and indomethacin) and catalase and accelerated by MK-447. These results incriminate both hydrogen peroxide and the hydroxyl radical as mediators of neutrophil-induced myocardial dysfunction. A test of this hypothesis in vivo was performed by neutrophil-depleting dogs with anti-canine leukocyte antisera prior to coronary artery ligation. Following 6 hr of reperfusion, there was a 43% reduction in infarct size compared to non-immune-sera-injected animals. We conclude that oxygen free radicals generated by neutrophils are capable of inducing significant myocardial injury and play an important role in the pathophysiology of ischemia-reperfusion injury.

Keywords

ATPase Activity Phorbol Myristate Acetate Phorbol Myristate Acetate Sarcoplasmic Reticulum Calcium Neutrophil Depletion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Michael L. Hess
    • 1
  • G. Thomas Rowe
    • 1
  • Martin Caplan
    • 1
  • Joseph L. Romson
    • 2
  • Benedict Lucchesi
    • 2
  1. 1.Department of Medicine (Cardiology)Medical College of VirginiaRichmondUSA
  2. 2.Department of PharmacologyUniversity of Michigan School of MedicineAnn ArborUSA

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