Effect of E4031, a class III antiarrhythmic drug, on ischemia- and reperfusion-induced arrhythmias in isolated rat hearts

Ken Shinmura, Masato Tani, Hiroshi Hasegawa, Yoshinori Ebihara, Yoshiro Nakamura

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The delayed outward rectifier K+ channel has a role in the increase in automaticity of myocytes under pathophysiological conditions. The purpose of the present study was to clarify the effect of blockade of outward recitifier K+ channels by a class III antiarrhythmic drug, E4031, on ischemia- and reperfusion-induced arrhythmias. Ion fluxes, energy metabolites and cardiac function were measured and the epicardial electrocardiograms of Langendorff-perfused rat hearts were recorded during initial perfusion, global or regional ischemia and reperfusion. 10-7 M of E4031 administered during the initial perfusion did not prolong the QT interval, but slowed the heart rate (Control: 222, E4031: 183 bpm, p < 0.05), increased myocardial 45Ca2+ uptake (Control: 2.1, E4031: 2.9 μmol/g dwt, p < 0.05) and attenuated the loss of intracellular K+ during ischemia (Control: 238, E4031: 248 μmol/g dwt, P < 0.05). E4031 tended to reduce ischemia-induced ventricular tachyarrhythmias (Control: 60, E4031: 30%, n.s.), but reperfusion-induced ventricular tachyarrhythmias were sustained longer by the administration of E4031 (Control: 255, E4031: 623 sec, p < 0.05). Prior exposure to E4031 decreased the depletion of high energy phosphates during ischemia, but suppressed their recovery during reperfusion. These results suggest that the attenuated loss of K+ from the ischemic myocardium and the decrease in heart rate by E4031 contributed to the reduction of ischemia-induced arrhythmias. However, the increase in myocardial Ca2+ uptake and altered energy metabolism may be responsible for the increase in reperfusion-induced arrhythmias.

Original languageEnglish
Pages (from-to)183-197
Number of pages15
JournalJapanese Heart Journal
Volume39
Issue number2
Publication statusPublished - 1998 Mar

Fingerprint

Anti-Arrhythmia Agents
Reperfusion
Cardiac Arrhythmias
Ischemia
Tachycardia
Perfusion
Heart Rate
Muscle Cells
Energy Metabolism
Myocardium
Electrocardiography
Phosphates
Ions

Keywords

  • Antiarrhythmic drug
  • Arrhythmia
  • Ca
  • Ischemia
  • K channel
  • Reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Effect of E4031, a class III antiarrhythmic drug, on ischemia- and reperfusion-induced arrhythmias in isolated rat hearts. / Shinmura, Ken; Tani, Masato; Hasegawa, Hiroshi; Ebihara, Yoshinori; Nakamura, Yoshiro.

In: Japanese Heart Journal, Vol. 39, No. 2, 03.1998, p. 183-197.

Research output: Contribution to journalArticle

Shinmura, K, Tani, M, Hasegawa, H, Ebihara, Y & Nakamura, Y 1998, 'Effect of E4031, a class III antiarrhythmic drug, on ischemia- and reperfusion-induced arrhythmias in isolated rat hearts', Japanese Heart Journal, vol. 39, no. 2, pp. 183-197.
Shinmura, Ken ; Tani, Masato ; Hasegawa, Hiroshi ; Ebihara, Yoshinori ; Nakamura, Yoshiro. / Effect of E4031, a class III antiarrhythmic drug, on ischemia- and reperfusion-induced arrhythmias in isolated rat hearts. In: Japanese Heart Journal. 1998 ; Vol. 39, No. 2. pp. 183-197.
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