Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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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)
  • Published : 2005.03.01
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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

References

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