KB-R7943, a Na+/Ca2+ Exchange Inhibitor, Does Not Suppress Ischemia/Reperfusion Arrhythmias nor Digitalis Arrhythmias in Dogs.

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  • Miyamoto Shigeki
    Department of Pharmacology, University of Yamanashi, Faculty of Medicine
  • Zhu Bing-Mei
    Department of Pharmacology, University of Yamanashi, Faculty of Medicine
  • Kamiya Kazunori
    Department of Pharmacology, University of Yamanashi, Faculty of Medicine
  • Nagasawa Yoshinobu
    Department of Pharmacology, University of Yamanashi, Faculty of Medicine
  • Hashimoto Keitaro
    Department of Pharmacology, University of Yamanashi, Faculty of Medicine

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  • KB-R7943, a Na〔+〕/Ca〔2+〕 Exchange Inhibitor, Does Not Suppress Ischemia/Reperfusion Arrhythmias nor Digitalis Arrhythmias in Dogs

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KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate) has been used as a pharmacological tool to block the Ca2+ influx-mode of the Na+/Ca2+ exchanger, which is thought to contribute to ischemia/reperfusion and digitalis arrhythmias. We examined effects of KB-R7943 on ischemia/reperfusion arrhythmias in beagle dogs anesthetized with sodium pentobarbital. Lead II ECG and BP were measured. KB-R7943 or the solvent (10% DMSO) was injected i.v. as a bolus, and 5 min later, the left anterior descending coronary artery was occluded for 30 min followed by reperfusion. KB-R7943 at 5 or 10 mg/kg increased BP without changing ECG parameters including the heart rate. Although 5 mg/kg KB-R7943 deceased the number of arrhythmic beats during the ischemic period, mortality due to ischemia/reperfusion was not decreased by KB-R7943 (5 and 10 mg/kg). KB-R7943 at 5 mg/kg also did not suppress the ouabain-induced arrhythmias. These negative results suggest that Na+/Ca2+ exchange inhibition may not be a useful strategy of suppressing arrhythmias.<br>

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