The extended acute myocardial ischemia (AMI) results in cardiac myocytes death. In the present study, we show that lactam pyridine derivative, SK-D80375, have the effects on cell survival in hypoxic cardiomyocytes and might be used as an anti-ischemic drug. The lactam pyridine derivatives are inhibitors of the late sodium current, which decreases sodium-dependent intracellular calcium overload in ischemia/reperfusion-injured hearts. We found that pretreatment with SK-D80375 significantly decreased the level of intracellular Ca2+and the expression level of the Na+-Ca2+exchanger by 39±2.5% and 19±0.5%, respectively in hypoxic cardiomyocytes compared to untreated controls. In addition, the expression level of sarcoplasmic reticulum Ca2+ATPase 2a was significantly increased by 37±1.5% in SK-D80375-treated hypoxic cardiomyocytes compared to untreated controls. The induction of Hsp70 was observed in SK-D80375-treated hypoxic cardiomyocytes with dose-dependent manner and the highest level of Hsp70 was induced at the concentration of 2.5 μM SK-D80375. The echocardiographic analysis showed that heart function was significantly improved in SK-D80375-injected ischemic hearts. These results demonstrate that lactam pyridine derivative, SK-D80375, have beneficial effects on hypoxia-induced cell death, therefore, might be used as a novel anti-ischemia drug.
|Number of pages||7|
|Journal||Tissue Engineering and Regenerative Medicine|
|Publication status||Published - 2009 Oct|
All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Biomedical Engineering