Prevention of postischemic myocardial reperfusion injury by the combined treatment of NCX-4016 and Tempol

Vijay Kumar Kutala, Mahmood Khan, Rajarsi Mandal, Vandana Potaraju, Giuseppe Colantuono, Damodar Kumbala, Periannan Kuppusamy

Research output: Contribution to journalArticle

Abstract

Nitric oxide (NO) plays a protective role in myocardial ischemia-reperfusion (I/R) injury. However, the concomitant production of superoxide and other reactive oxygen species (ROS) during I/R may diminish the bioavailability of NO and hence compromise the beneficial effects. The objective of this study was to investigate the protective effect of the coadministration of NCX-4016 [2-(acetyloxy)benzoic acid 3-(nitrooxymethyl)phenyl ester] (an NO donor) with antioxidants Tempol, superoxide dismutase (SOD), or urate on I/R injury. Isolated rat hearts, perfused with Krebs-Henseleit buffer, were subjected to 30 minutes of global ischemia, followed by 45 minutes of reperfusion. Before the induction of ischemia, the hearts were infused for 1 minute with NCX-4016 (100 μM) either alone or in combination with Tempol (100 μM), SOD (200 U/mL), or urate (100 μM). Hearts pretreated with NCX-4016 showed a significantly enhanced recovery of function and decreased infarct size and LDH/CK release compared with the controls. However, treatment of hearts with NCX-4016 + Tempol, SOD, or urate showed a significantly enhanced recovery of heart function compared with NCX-4016 alone. The treatment of hearts with NCX-4016 + Tempol showed significantly enhanced NO generation and decreased ROS and dityrosine (a marker of peroxynitrite) formation. In conclusion, NCX-4016 in combination with Tempol demonstrated significant cardioprotection and, thus, may offer a novel therapeutic strategy to prevent I/R-mediated myocardial injury.

Original languageEnglish (US)
Pages (from-to)79-87
Number of pages9
JournalJournal of cardiovascular pharmacology
Volume48
Issue number3
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

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Keywords

  • Antioxidant
  • Ischemia-reperfusion injury
  • NCX-4016
  • Nitric oxide
  • Nitro-aspirin
  • Oxidative stress
  • Tempol

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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