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Peroxynitrite aggravates myocardial reperfusion injury in the isolated perfused rat heart.

AbstractOBJECTIVE:
This study examined the effects of peroxynitrite (ONOO-) on cardiac function and cellular injury following ischemia (30 min) and reperfusion (60 min) in isolated perfused rat hearts.
METHODS:
3-Morpholinosydnonimine (SIN-1, 0.1 mM), an ONOO- donor, was administered alone or combined with superoxide dismutase (SOD, 300 U/ml) or glutathione (GSH, 1 mM) at the time of reperfusion.
RESULTS:
Administration of SIN-1 alone significantly aggravated post-ischemic myocardial injury characterized by depressed cardiac function recovery (p < 0.05 vs. vehicle), increased lactic dehydrogenase (LDH) and creatine kinase (CK) release (p < 0.01 vs. vehicle), and enlarged necrotic size (p < 0.01 vs. vehicle). The co-administration of either SOD to decrease the formation of ONOO-, or GSH to increase the detoxification of ONOO-, completely blocked the detrimental effects of SIN-1 and exerted significant cardioprotective effects against reperfusion injury.
CONCLUSION:
These results suggest that ONOO- may play a significant role in postischemic myocardial injury.
AuthorsX L Ma, B L Lopez, G L Liu, T A Christopher, H Ischiropoulos
JournalCardiovascular research (Cardiovasc Res) Vol. 36 Issue 2 Pg. 195-204 (Nov 1997) ISSN: 0008-6363 [Print] NETHERLANDS
PMID9463631 (Publication Type: Journal Article)
Chemical References
  • Nitrates
  • Vasodilator Agents
  • peroxynitric acid
  • linsidomine
  • Molsidomine
  • L-Lactate Dehydrogenase
  • Superoxide Dismutase
  • Creatine Kinase
  • Glutathione
Topics
  • Animals
  • Creatine Kinase (metabolism)
  • Glutathione (pharmacology)
  • L-Lactate Dehydrogenase (metabolism)
  • Male
  • Molsidomine (analogs & derivatives, pharmacology)
  • Myocardial Contraction (drug effects)
  • Myocardial Reperfusion Injury (etiology)
  • Myocardium (enzymology)
  • Nitrates (antagonists & inhibitors, toxicity)
  • Perfusion
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase (pharmacology)
  • Vasodilator Agents (pharmacology)

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