Novel Lactam Type Pyridine Derivatives Improves Myocardium Dysfunction Derived from Ischemic Injury

作者：Kim Kyung Eun; Song Heesang; Cha Minji; Song Byeong Wook; Choi Eunju; Ham Onju; Lee Chang Yeon; Choi Seong Yong; Lee Se Yeon; Jang Yangsoo; Hwang Ki Chul^*

来源：Tissue Engineering and Regenerative Medicine, 2009, 6(13): 1191-1197.

• cardiomyocyte
• lactam pyridine derivative
• ischemia
• apoptosis

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 oil cell Survival in hypoxic cardiomyocytes and might be used as all 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 Ca(2+) and the expression level of the Na(+)-Ca(2+) exchanger by 39 +/- 2.5% and 1 9 +/- 0.5%, respectively in hypoxic cardiomyocytes compared to untreated controls. In addition, the expression level of sarcoplasmic reticulum Ca(2+) 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 mu M 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 oil hypoxia-induced cell death, therefore, might be used as a novel anti-ischemia drug.

• 出版日期2009-10