Effects of [5-(2-Methoxy-5-fluorophenyl)furan-2-ylcarbonyl]guanidine (KR-32560), a Novel Sodium/Hydrogen Exchanger-1 Inhibitor, on Myocardial Infarct Size and Ventricular Arrhythmias in a Rat Model of Ischemia/Reperfusion Heart Injury

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概要

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• 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 μM) 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 (mm3/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.

• 社団法人 日本薬理学会の論文
• 2005-08-20

著者

• Yun Yeo-Pyo

  College of Pharmacy, Chungbuk National University

• Yoo Sung-eun

  Medical Science Division Korea Research Institute Of Chemical Technology

• Yoo S‐e

  Korea Res. Inst. Of Chemical Technol. Daejon Kor

• Yun Yeo-pyo

  Coll. Of Pharmacy Chungbuk National Univ.

• Yun Yeo-pyo

  College Of Pharmacy Research Center For Bioresource And Health Chungbuk National University

• Yun Y‐p

  Chungbuk National Univ. Cheongju Kor

• Yun Yeo-pyo

  College Of Pharmacy Chungbuk National University

• Shin Hwa-sup

  Department Of Applied Biochemistry Division Of Life Science College Of Biomedical And Health Science

• PARK JUNG-WOO

  Department of Earth and Environmental Sciences, Korea University

• Yi Kyu-yang

  Medical Science Division Korea Research Institute Of Chemical Technology

• CHUNG Hun-Jong

  Pediatric Department, Chungju Hospital, Konkuk Medical School, Konkuk University

• KWON Suk-Hyung

  Rexgene Biotech Co., Ltd.

• ROH Hui-Yul

  Department of Applied Biochemistry, Division of Life Science, College of Biomedical and Health Scien

• JUNG In-Sang

  Department of Applied Biochemistry, Division of Life Science, College of Biomedical and Health Scien

• Roh Hui-yul

  Department Of Applied Biochemistry Division Of Life Science College Of Biomedical And Health Science

• Jung In-sang

  Department Of Applied Biochemistry Division Of Life Science College Of Biomedical And Health Science

• Kwon Suk-hyung

  Rexgene Biotech Co. Ltd.

• Chung Hun-jong

  Pediatric Department Chungju Hospital Konkuk Medical School Konkuk University

• Park Jung-woo

  Department Of Applied Biochemistry Division Of Life Science College Of Biomedical And Health Science

• Yun Yeo-pyo

  College Of Pharmacy Cbitrc College Of Pharmacy And Medical Research Center Chungbuk National Univers

• Yun Yeo-Pyo

  College of Pharmacy and Medical Research Center, Chungbuk National University

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