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

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 mu M), 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-mereaptopropionyl)-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. (c) 2006 Elsevier Inc. All rights reserved.