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

Fingerprint

Myocardial Reperfusion Injury
Ischemia
Uric Acid
Superoxide Dismutase
Nitric Oxide
Recovery of Function
Reperfusion Injury
Reperfusion
Reactive Oxygen Species
Peroxynitrous Acid
Nitric Oxide Donors
nitroaspirin
tempol
Superoxides
Biological Availability
Aspirin
Myocardial Ischemia
Esters
Antioxidants

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Prevention of postischemic myocardial reperfusion injury by the combined treatment of NCX-4016 and Tempol. / Kutala, Vijay Kumar; Khan, Mahmood; Mandal, Rajarsi; Potaraju, Vandana; Colantuono, Giuseppe; Kumbala, Damodar; Kuppusamy, Periannan.

In: Journal of Cardiovascular Pharmacology, Vol. 48, No. 3, 01.09.2006, p. 79-87.

Research output: Contribution to journalArticle

Kutala, Vijay Kumar ; Khan, Mahmood ; Mandal, Rajarsi ; Potaraju, Vandana ; Colantuono, Giuseppe ; Kumbala, Damodar ; Kuppusamy, Periannan. / Prevention of postischemic myocardial reperfusion injury by the combined treatment of NCX-4016 and Tempol. In: Journal of Cardiovascular Pharmacology. 2006 ; Vol. 48, No. 3. pp. 79-87.
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