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

• Published in: Journal of Pharmacological Sciences 2005, Vol.98(4), pp.439-449
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Animals; arrhythmia; Arrhythmias, Cardiac - etiology; Arrhythmias, Cardiac - physiopathology; Arrhythmias, Cardiac - prevention & control; cardioprotection; Cardiotonic Agents - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Guanidines - chemistry; Guanidines - pharmacology; Heart Ventricles; infarction; KR-32560; Male; Molecular Structure; Myocardial Infarction - pathology; Myocardial Infarction - prevention & control; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Rabbits; Rats; Rats, Sprague-Dawley; sodium hydrogen exchanger isoform-1; Sodium-Hydrogen Exchangers - antagonists & inhibitors; Time Factors
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.FP0050078

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