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Antiarrhythmic Effects of KR-32570, a Novel Na+-H+ Exchanger Inhibitor, on Ischemia/Reperfusion-Induced Arrhythmias  

Hwang, Geum-Shil (Medicinal Science Division, Korea Research Institute of Chemical Technology)
Seo, Ho-Won (Medicinal Science Division, Korea Research Institute of Chemical Technology)
Lee, Kyu-Yang (Medicinal Science Division, Korea Research Institute of Chemical Technology)
Lee, Sun-Kyung (Medicinal Science Division, Korea Research Institute of Chemical Technology)
Yoo, Sung-Eun (Medicinal Science Division, Korea Research Institute of Chemical Technology)
Lee, Byung-Ho (Medicinal Science Division, Korea Research Institute of Chemical Technology)
Publication Information
Biomolecules & Therapeutics / v.13, no.1, 2005 , pp. 20-25 More about this Journal
Abstract
The present study was performed to evaluate antiarrhythmic effects of KR-32570, a novel inhibitor of sodium hydrogen exchanger subtype-1 (NHE-1), in rat arrhythmia induced by focal ischemia and reperfusion. During ischemia, KR-32570 significantly decreased the number of premature ventricular contraction (PVC) from 152.0 times to 75.5, 52.4 and 20.0 times for 0.1, 0.3 and 1.0 mg/kg, respectively (p<0.05) and the duration of ventricular tachycardia (VT) from 88.1 s to 35.8, 7.7 and 1.3 s, respectively(p<0.05) in anesthetized rats subjected to 10-min coronary occlusion of coronary artery. Similarlt to ischemia-induced arrhythmia, KR-32570 significantly decreased reperfusion-induced arrhythmia including PVC (41.3, 21.5, 11.3 and 6.6 times at vehicle, 0.1, 0.3 and 1.0 mg/kg, respectively, p<0.05) and VT (100.5, 64.2, 25.8 and 25.2 s, respectively, p<0.05), and VF (86.9, 27.5, 6.9 and 0 s, respectively, p<0.05). Moreover, KR-32570 dose-dependently decreased the incidence of mortality occurring after reperfusion (41, 27, 18 and 0% at vehicle, 0.1, 0.3, 1.0 mg/kg, respectively). These results suggest that KR-32570 has a potent antiarrhythmic effect in rat arrhythmia induced by ischemia and reperfusion.
Keywords
antiarrhythmic effect; sodium hydrogen exchanger; KR-32570;
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