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

JC FANTINELLI; HE CINGOLANI; SM MOSCA

CARDIOVASCULAR PATHOLOGY

ELSEVIER SCIENCE INC

Año: 2006 vol. 15 p. 179 - 184

1054-8807

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 AM), significantly diminished infarct size (15.1F2.4% vs. 31F2% in untreated hearts). The administration of a bscavengerQ of hydroxyl radical, N-(2- mercaptopropionyl)-glycine (2 mM), decreased infarct size in an extent similar to that of cariporide (18F3%). The combination cariporide+N-(2-mercaptopropionyl)-glycine did not produce additional protection (17F1.7%). 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 (1012F144 nmol/g) decreased to 431F81, 390F82, and 433F41 after cariporide, N-(2-mercaptopropionyl)-glycine, and cariporide+N-(2-mercaptopropionyl)-glycine treatments, respectively.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 AM), significantly diminished infarct size (15.1F2.4% vs. 31F2% in untreated hearts). The administration of a bscavengerQ of hydroxyl radical, N-(2- mercaptopropionyl)-glycine (2 mM), decreased infarct size in an extent similar to that of cariporide (18F3%). The combination cariporide+N-(2-mercaptopropionyl)-glycine did not produce additional protection (17F1.7%). 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 (1012F144 nmol/g) decreased to 431F81, 390F82, and 433F41 after cariporide, N-(2-mercaptopropionyl)-glycine, and cariporide+N-(2-mercaptopropionyl)-glycine treatments, respectively.+/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 AM), significantly diminished infarct size (15.1F2.4% vs. 31F2% in untreated hearts). The administration of a bscavengerQ of hydroxyl radical, N-(2- mercaptopropionyl)-glycine (2 mM), decreased infarct size in an extent similar to that of cariporide (18F3%). The combination cariporide+N-(2-mercaptopropionyl)-glycine did not produce additional protection (17F1.7%). 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 (1012F144 nmol/g) decreased to 431F81, 390F82, and 433F41 after cariporide, N-(2-mercaptopropionyl)-glycine, and cariporide+N-(2-mercaptopropionyl)-glycine treatments, respectively.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 AM), significantly diminished infarct size (15.1F2.4% vs. 31F2% in untreated hearts). The administration of a bscavengerQ of hydroxyl radical, N-(2- mercaptopropionyl)-glycine (2 mM), decreased infarct size in an extent similar to that of cariporide (18F3%). The combination cariporide+N-(2-mercaptopropionyl)-glycine did not produce additional protection (17F1.7%). 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 (1012F144 nmol/g) decreased to 431F81, 390F82, and 433F41 after cariporide, N-(2-mercaptopropionyl)-glycine, and cariporide+N-(2-mercaptopropionyl)-glycine treatments, respectively.Results: Treatment during the first 20 min of reperfusion with a selective inhibitor of Na+/H+exchanger 1 isoform, HOE 642 (cariporide; 10 AM), significantly diminished infarct size (15.1F2.4% vs. 31F2% in untreated hearts). The administration of a bscavengerQ of hydroxyl radical, N-(2- mercaptopropionyl)-glycine (2 mM), decreased infarct size in an extent similar to that of cariporide (18F3%). The combination cariporide+N-(2-mercaptopropionyl)-glycine did not produce additional protection (17F1.7%). 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 (1012F144 nmol/g) decreased to 431F81, 390F82, and 433F41 after cariporide, N-(2-mercaptopropionyl)-glycine, and cariporide+N-(2-mercaptopropionyl)-glycine treatments, respectively.+/H+exchanger 1 isoform, HOE 642 (cariporide; 10 AM), significantly diminished infarct size (15.1F2.4% vs. 31F2% in untreated hearts). The administration of a bscavengerQ of hydroxyl radical, N-(2- mercaptopropionyl)-glycine (2 mM), decreased infarct size in an extent similar to that of cariporide (18F3%). The combination cariporide+N-(2-mercaptopropionyl)-glycine did not produce additional protection (17F1.7%). 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 (1012F144 nmol/g) decreased to 431F81, 390F82, and 433F41 after cariporide, N-(2-mercaptopropionyl)-glycine, and cariporide+N-(2-mercaptopropionyl)-glycine treatments, respectively.1F2.4% vs. 31F2% in untreated hearts). The administration of a bscavengerQ of hydroxyl radical, N-(2- mercaptopropionyl)-glycine (2 mM), decreased infarct size in an extent similar to that of cariporide (18F3%). The combination cariporide+N-(2-mercaptopropionyl)-glycine did not produce additional protection (17F1.7%). 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 (1012F144 nmol/g) decreased to 431F81, 390F82, and 433F41 after cariporide, N-(2-mercaptopropionyl)-glycine, and cariporide+N-(2-mercaptopropionyl)-glycine treatments, respectively.8F3%). The combination cariporide+N-(2-mercaptopropionyl)-glycine did not produce additional protection (17F1.7%). 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 (1012F144 nmol/g) decreased to 431F81, 390F82, and 433F41 after cariporide, N-(2-mercaptopropionyl)-glycine, and cariporide+N-(2-mercaptopropionyl)-glycine treatments, respectively.7F1.7%). 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 (1012F144 nmol/g) decreased to 431F81, 390F82, and 433F41 after cariporide, N-(2-mercaptopropionyl)-glycine, and cariporide+N-(2-mercaptopropionyl)-glycine treatments, respectively.2F144 nmol/g) decreased to 431F81, 390F82, and 433F41 after cariporide, N-(2-mercaptopropionyl)-glycine, and cariporide+N-(2-mercaptopropionyl)-glycine treatments, respectively.3F41 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.The present data support the conclusion that the cardioprotective effect of cariporide is associated with diminution of oxidative stress.