Effective inhibition of cardiomyocyte apoptosis through the combination of @entity1481 and @entity898 in a XXXX model of @entity741 and reperfusion injury.

@entity32 @entity21078 @entity35 @entity63 @entity898 @entity1234 @entity1188 @entity1481 @entity741 @entity2904 @entity4124 @entity1865
OBJECTIVE: Apoptosis is the early and predominant form of cell death in infarcted myocardia. The aim of the study was to investigate the effects of @entity1481 ( @entity2904 ) and @entity898 (NAC), used alone or in combination, on oxidative stress, @entity1188 size, and @entity63 -reperfusion (IR)-induced cardiomyocyte apoptosis in a @entity35 model of @entity741 . METHODS AND RESULTS: Myocardial IR was established by ligating an area under the left main coronary artery for 30  min followed by 3  h of reperfusion. Saline (1  ml/kg), NAC (50, 150  mg/kg), or @entity2904 (3, 5  mg/kg) was intravenously injected during the middle of the @entity63 period. At the end of the reperfusion, blood samples were collected from the animals to measure serum M30 and M65 levels, which are markers of cell death, the @entity21078 level, which is a marker of @entity32 , and the @entity1234 ( @entity1865 ) level, which is a marker of oxidative stress. The @entity1188 size was evaluated as the ratio of the @entity1188 area to the risk area. Apoptotic activation was assessed by @entity4124 immunostaining and a TUNEL assay. @entity2904 and NAC, either alone or in combination, significantly reduced serum @entity1865 levels, @entity1188 area and apoptotic activity compared to those observed in saline group. Interestingly, the @entity1188 area was more smaller in @entity2904 (3 and 5  mg/kg) injected groups (9.72      1.3% and 9.96      2.3%) than those observed in NAC (50 and 150  mg/kg) (16.1      2.5% and 19.1      2.14%) or @entity2904 (5  mg/kg)- NAC (150  mg/kg) combination groups (16.9      1.6%). However, the apoptotic activity was reduced more significantly in the combination of @entity2904 (5  mg/kg)-NAC (50  mg/kg) compared to @entity2904 -only group. Neither @entity2904 or NAC treatments nor the combination of the drugs significantly affected serum M30, M65 and @entity21078 levels. CONCLUSION: Intravenous NAC and @entity2904 administration decreased oxidative stress, @entity1188 area and apoptotic activity in a @entity35 model of IR. Although the combination treatment was more effective in reducing the apoptotic activity than either treatment groups alone, @entity2904 treatment was more successful in reducing the @entity1188 area than NAC or combination treatments. Present results suggest that, in addition to mechanical attempts to secure myocardial reperfusion, the use of @entity2904 and NAC may help to reduce IR injury.
