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Cardioprotective effect of a novel cyclohexane dicarboximide derivative, ST‐6, against ischemia/reperfusion injury
Author(s) -
Takeo Satoshi,
Kajiwara Hiroshi,
Taaka Kouichi,
Nasa Yoshihisa,
Nakajima Yasuo,
Ohya Yumiko,
Kaizuka Yukiko
Publication year - 2000
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/1098-2299(20000901)51:1<20::aid-ddr3>3.0.co;2-w
Subject(s) - ischemia , cardioprotection , reperfusion injury , ventricular pressure , cardiology , medicine , creatine , creatine kinase , anesthesia , pharmacology , chemistry , blood pressure
Blockade of sodium overload during ischemia and reperfusion plays an important role in cardioprotection. The present study was undertaken to determine whether or not a novel cyclohexane dicarboximide derivative, ST‐6, which reveals sodium channel blockade, may protect the heart from ischemia/reperfusion injury. Isolated rat hearts were subjected to 30 min of ischemia followed by a 60‐min reperfusion. Treatment with 10 and 30 μM ST‐6 enhanced the postischemic recovery of left ventricular developed pressure, attenuated the rise in left ventricular end‐diastolic pressure, and restored high‐energy phosphate levels of the ischemic/reperfused heart. This improvement was associated with reduction of the release of creatine kinase and purine nucleosides and bases from the reperfused heart. Tissue sodium content of the ischemic as well as reperfused hearts was increased. This increase was partially reversed by treatment with ST‐6. ST‐6 had the ability to reduce V max of the action potential of the left ventricular muscle. These results suggest that this agent is capable of reducing ischemia/reperfusion injury of the heart, probably due to attenuation in sodium overload during ischemia and reperfusion. Drug Dev. Res. 51:20–28, 2000. © 2000 Wiley‐Liss, Inc.