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

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. 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. 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. The present data support the conclusion that the cardioprotective effect of cariporide is associated with diminution of oxidative stress.