The effects of a novel cyclohexane dicarboximide derivative, ST-6, on hypoxia/reoxygenation injury in perfused rat heart.
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 hypoxia followed 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-i soindol-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 bases 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.
Takeo
S
S
Department of Pharmacology, Tokyo University of Pharmacy & Life Science, Hachioji, Japan. takeos@ps.toyaku.ac.jp
Tanonaka
K
K
Kajiwara
H
H
Miyake
K
K
Antoku
F
F
Mori
H
H
D000818:Animals; D000860:Hypoxia / Q000503:physiopathology / Q000517:prevention & control*; D007094:Imides / Q000494:pharmacology*; D054833:Isoindoles; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats
C414319:2-(4-(4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl)butyl)hexahydro-1H-isoindol-1,3(2H)-dione; D007094:Imides; D054833:Isoindoles; D010880:Piperidines