2000 Volume 23 Issue 6 Pages 712-716
The present study was undertaken to test if some cyclohexane dicarboximide derivatives may have a cardioprotective effect against hypoxia/reoxygenation injury. Isolated rat hearts were subjected to 20-min of hypoxiafollowed by 45-min reoxygenation, and their recovery of post-hypoxic cardiac contractile function was examined.Treatment with agents was carried out from 3 min after the onset of hypoxia to the end of hypoxia (17 min during hypoxia). Among the 17 compounds, 2-[4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]butyl]hexahydro-1H-isoindol-1, 3(2H)-dione (ST-6) showed a significant enhancement of post-hypoxic contractile force. This was associated with attenuation of the releases of creatine kinase and purine nucleosides and based from the perfused heart. Hypoxia-induced increase in myocardial sodium and decrease in potassium ion content was suppressed by ST-6 treatment. The results suggest that ST-6 is capable of protecting the heart against hypoxia/reoxygenation injury possibly through a mechanism by which sodium overload during hypoxia is suppressed.
