Novel Lactam Type Pyridine Derivatives Improves Myocardium
Dysfunction Derived from Ischemic Injury
Authors
Kyung-Eun Kim ; Heesang Song ; Minji Cha ; Byeong-Wook Song ; Eunju Choi ; Onju Ham ; Chang Yeon Lee ; Seong Yong Choi ; Se-Yeon Lee ; Yangsoo Jang ; Ki-Chul Hwang
Citation
TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Vol.6(13) : 1191-1197, 2009
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