Cardiovascular Drugs and Therapy

, Volume 2, Issue 6, pp 761–769

Myocardial ischemia and reperfusion: The role of oxygen radicals in tissue injury

  • Steven W. Werns
  • Benedict R. Lucchesi
Focused Section on Acute Myocardial Ischemia and Infarction

DOI: 10.1007/BF00133206

Cite this article as:
Werns, S.W. & Lucchesi, B.R. Cardiovasc Drug Ther (1989) 2: 761. doi:10.1007/BF00133206

Summary

Thrombolytic therapy has gained widespread acceplance as a means of treating coronary artery thrombosis in patients with acute myocardial infarction. Although experimental data have demonstrated that timely reperfusion limits the extent of infarction caused by regional ischemia, there is growing evidence that reperfusion is associated with an inflammatory response to ischemia that exacerbates the tissue injury. Ischemic myocardium releases archidonate and complement-derived chemotactic factors, e.g., leukotriene B4 and C5a, which attract and activate neutrophils. Reperfusion of ischemic myocardium accelerates the influx of neutrophils, which release reactive oxygen products, such as superoxide anion and hydrogen peroxide, resulting in the formation of a hydroxyl radical and hypochlorous acid. The latter two species may damage viable endothelial cells and myocytes via the peroxidation of lipids and oxidation of protein sulfhydryl groups, leading to perturbations of membrane permeability and enzyme function. Neutrophil depletion by antiserum and inhibition of neutrophil function by drugs, e.g., ibuprofen, prostaglandins (prostacyclin and PGE1), or a monoclonal antibody, to the adherence-promoting glycoprotein Mo-1 receptor, have been shown to limit the extent of canine myocardial injury due to coronary artery occlusion/reperfusion. Recent studies have challenged the hypothesis that xanthine-oxidase-derived oxygen radicals are a cause of reperfusion injury. Treatment with allopurinol or oxypurinol may exert beneficial effects on ischemic myocardium that are unrelated to the inhibition of xanthine oxidase. Furthermore, the human heart may lack xanthine oxidase activity. Further basic research is needed, therefore, to clarify the importance of xanthine oxidase in the pathophysiology of reperfusion injury. Current data are highly suggestive of a deleterious role of the neutrophil in organ reperfusion and justify consideration of the clinical investigation of neutrophil inhibitors in patients receiving thrombolytic agents during the evolution of an acute myocardial infarction.

Key Words

myocardial ischemia myocardial infarction reperfusion injury oxygen free radicals neutrophils xanthine oxidase 

Copyright information

© Kluwer Academic Publishers 1989

Authors and Affiliations

  • Steven W. Werns
    • 1
  • Benedict R. Lucchesi
    • 2
  1. 1.Department of Internal Medicine(Division of Cardiology)The University of Michigan Medical SchoolAnn Arbor
  2. 2.Department of PharmacologyThe University of Michigan Medical SchoolAnn Arbor
  3. 3.Department of PharmacologyThe University of Michigan Medical SchoolAnn ArborMichigan

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