Park Jung-Woo, Roh Hui-Yul, Jung In-Sang, Yun Yeo-Pyo, Yi Kyu-Yang, Yoo Sung-Eun, Kwon Suk-Hyung, Chung Hun-Jong, Shin Hwa-Sup
Department of Applied Biochemistry, Division of Life Science, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Korea.
J Pharmacol Sci. 2005 Aug;98(4):439-49. doi: 10.1254/jphs.fp0050078. Epub 2005 Aug 5.
The cardioprotective effects of the novel sodium/hydrogen exchanger-1 (NHE-1) inhibitor KR-32560 {[5-(2-methoxy-5-fluorophenyl)furan-2-ylcarbonyl]guanidine} were studied in an anesthetized rat model of 30-min ischemia / 2.5-h reperfusion heart injury. KR-32560 (0.01 - 1 microM) dose-dependently inhibited NHE-1-mediated rabbit platelet swelling induced by intracellular acidification. KR-32560 at 0.1 and 1.0 mg/kg (i.v. bolus, given 10 min before ischemia) reduced infarct size from 65.9% (control) to 49.7% and 32.7%, respectively, while reducing the extension of myocardial injury (mm(3)/g of left heart weight) from 405.1 (control) to 302.9 and 185.4, respectively (all P<0.05 vs control). KR-32560 dose-dependently reduced the total number of ventricular premature beats (VPBs) during ischemia from 510.2 (control) to 353.8 and 134.2 beats (all P<0.05, n = 6), while reducing ventricular tachycardia (VT) incidence from 49.3 (control) to 26.8 and 4.3 and VT duration from 249.2 s (control) to 150.5 and 26.7 s (all P<0.05, n = 6). KR-32560 dose-dependently reduced ventricular fibrillation (VF) incidence from 19.0 (control) to 9.2 and 1.2 and VF duration from 88.0 s to 34.5 and 2.8 s (all P<0.05, n = 6). KR-32560 also exerted similar effects on reperfusion arrhythmias, except for VPBs. These results indicate that KR-32560 may exert significant cardioprotective effects in ischemia/reperfusion heart injury.
在30分钟缺血/2.5小时再灌注心脏损伤的麻醉大鼠模型中，研究了新型钠/氢交换体-1（NHE-1）抑制剂KR-32560{[5-(2-甲氧基-5-氟苯基)呋喃-2-基羰基]胍}的心脏保护作用。KR-32560（0.01 - 1微摩尔）剂量依赖性地抑制细胞内酸化诱导的NHE-1介导的兔血小板肿胀。缺血前10分钟静脉推注0.1和1.0毫克/千克的KR-32560，梗死面积分别从65.9%（对照组）降至49.7%和32.7%，同时心肌损伤范围（左心重量的立方毫米/克）分别从405.1（对照组）降至302.9和185.4（与对照组相比，均P<0.05）。KR-32560剂量依赖性地将缺血期间室性早搏（VPB）总数从510.2（对照组）降至353.8和134.2次（均P<0.05，n = 6），同时室性心动过速（VT）发生率从49.3（对照组）降至26.8和4.3，VT持续时间从249.2秒（对照组）降至150.5和26.7秒（均P<0.05，n = 6）。KR-32560剂量依赖性地将心室颤动（VF）发生率从19.0（对照组）降至9.2和1.2，VF持续时间从88.0秒降至34.5和2.8秒（均P<0.05，n = 6）。除VPB外，KR-32560对再灌注心律失常也有类似作用。这些结果表明，KR-32560可能在缺血/再灌注心脏损伤中发挥显著的心脏保护作用。
