Na+/H+ exchanger inhibition at the onset of reperfusion decreases myocardial infarct size: role of reactive oxygen species

Juliana C. Fantinelli, Horacio E. Cingolani, Susana M. Mosca

Research output: Contribution to journalArticlepeer-review

Abstract

Background: A burst of reactive oxygen species and activation of Na+/H+ exchanger take place at the beginning of reperfusion. The aim of this study was to assess the possible interrelation of the inhibition of Na+/H+ exchanger and reactive oxygen species about the determination of myocardial infarct size. Methods: Isolated rat hearts were submitted to 40 min of coronary occlusion and 2 h of reperfusion. Infarct size was determined through triphenyltetrazolium chloride staining technique and was expressed as a percentage of risk area. Lipid peroxidation, as a marker of oxidative stress, was estimated by the concentration of thiobarbituric reactive substances. Results: Treatment during the first 20 min of reperfusion with a selective inhibitor of Na+/H+ exchanger 1 isoform, HOE 642 (cariporide; 10 μM), significantly diminished infarct size (15.1±2.4% vs. 31±2% in untreated hearts). The administration of a "scavenger" of hydroxyl radical, N-(2-mercaptopropionyl)-glycine (2 mM), decreased infarct size in an extent similar to that of cariporide (18±3%). The combination cariporide+N-(2-mercaptopropionyl)-glycine did not produce additional protection (17±1.7%). Each intervention [HOE 642 or N-(2-mercaptopropionyl)-glycine] and its combination improved the postischemic recovery of myocardial systolic and diastolic functions in a similar extent. The content of the thiobarbituric reactive substances of untreated hearts (1012±144 nmol/g) decreased to 431±81, 390±82, and 433±41 after cariporide, N-(2-mercaptopropionyl)-glycine, and cariporide+N-(2-mercaptopropionyl)-glycine treatments, respectively. Conclusions: The present data support the conclusion that the cardioprotective effect of cariporide is associated with diminution of oxidative stress.

Original languageEnglish (US)
Pages (from-to)179-184
Number of pages6
JournalCardiovascular Pathology
Volume15
Issue number4
DOIs
StatePublished - Jul 2006

Keywords

  • Cariporide
  • Ischemia-reperfusion injury
  • MPG
  • NHE
  • ROS

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cardiology and Cardiovascular Medicine

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