Protective Effect of FR183998, a Na+/H+ Exchange Inhibitor, Against Postischemic Injury After Normothermic and Prolonged Hypothermic Ischemia in Isolated Perfused Rat Hearts

The Japanese Journal of Pharmacology

Toru Ozaki¹  Nobuhiro Yamamoto¹  Kazuhiro Maeda²  Jiro Seki¹  Toshio Goto¹  Fumihiro Ohara¹ 

[1] Department of Cardiovascular Disease, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.;Research Planning, Fujisawa Pharmaceutical Co., Ltd.

关键词: Cardioplegia;    FR183998;    Na+/H+ exchange;    Ischemia and reperfusion;    Hypothermia;   

DOI  :  10.1254/jjp.87.110

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(23)Cited-By(1)Inhibition of Na+/H+ exchanger has been reported to protect hearts from ischemia and reperfusion injury. However, the effect of Na+/H+ exchange inhibition on hypothermic ischemic injury has not been extensively studied and the results are inconsistent. The purpose of this study was to investigate whether inhibition of Na+/H+ exchange with FR183998 (5-(2,5-dichlorothiphen-3-yl)-3-[(2-dimethylaminoethyl)carbamoyl]benzoylguanidine dihydrochloride), a potent Na+/H+ exchange inhibitor, would show protective effects against postischemic cardiac dysfunction after hypothermic as well as normothermic ischemia and furthermore, after hypothermic cardioplegic arrest in isolated rat hearts. FR183998 (3.2 × 10−8 – 3.2 × 10−7 M) improved post-ischemic recovery of left ventricular developed pressure and suppressed the increase of left ventricular end diastolic pressure in a dose-dependent manner, after not only 45 min of normothermic ischemia but also 6 h of hypothermic ischemia. Furthermore, FR183998 (10−7 – 10 −6 M) significantly reduced creatine kinase release during reperfusion after 3 h of hypothermic ischemia with cardioplegia. These results indicate that FR183998 has a potent protective effect on postischemic cardiac dysfunction after normothermic and hypothermic ischemia, and also on reperfusion injury after hypothermic cardioplegic arrest, suggesting that its effect would be additive to cardioplegia.

【 授权许可】

Unknown