Identification of hydrogen peroxide and hydroxyl radicals as mediators of leukocyte-induced myocardial dysfunction. Limitation of infarct size with neutrophil inhibition and depletion
| Autor: | M L, Hess, G T, Rowe, M, Caplan, J L, Romson, B, Lucchesi |
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| Rok vydání: | 1985 |
| Předmět: |
Adenosine Triphosphatases
Male Free Radicals Hydroxyl Radical Neutrophils Superoxide Dismutase Myocardium Indomethacin Myocardial Infarction Ibuprofen Hydrogen Peroxide Butylated Hydroxytoluene Catalase Sarcoplasmic Reticulum Dogs Hydroxides Leukocytes Animals Tetradecanoylphorbol Acetate Calcium Mannitol |
| Zdroj: | Advances in myocardiology. 5 |
| ISSN: | 0270-4056 |
| Popis: | Neutrophil infiltration of the myocardium is an important component of such diverse disease 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. |
| Databáze: | OpenAIRE |
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