Effects of endothelin‐1 mRNA antisense oligodeoxynucleotides on ischemic arrhythmias in isolated rat hearts

Abstract

AbstractThe role of endothelin‐1 (ET‐1) in acute ischemic arrhythmia is controversial. To illustrate the involvement of cardiac ET‐1 in ischemic arrhythmia, the effects of ET‐1 mRNA antisense oligodeoxy‐nucleotides (AS‐ODNs) on acute ischemic arrhythmia were observed. ET‐1 AS‐ODN was injected i.v. in rats 2 h before the experimental procedure and the ischemic arrhythmia caused by occlusion of the left anterior descending (LAD) coronary artery was observed in the isolated perfused heart. The results show that: 1) In normal perfused rat hearts, a small number of ventricular ectopic beats (VEBs) were observed and neither ventricular tachycardia (VT) nor heart arrest occurred. 2) LAD occlusion elicited various ischemic arrhythmias in isolated hearts. No differences in the incidences or numbers of the arrhythmias were found between isolated hearts which had received normal saline (NS) and those which had received ET‐1 ODNs (sense‐ODN and scrambled‐ODN) in vivo. VT occurred in all hearts and the percentage of heart arrest was 33.3% in the NS group, 12.5% in the sense‐ODN group, and 25% in the scrambled ODN group. 3) ET‐1 AS‐ODN dose‐dependently decreased the incidence of VT, the arrhythmia score, the numbers of single VEBs and VT, and no heart arrest was observed in the hearts pretreated with ET‐1 AS‐ODN. These results demonstrated a contributory role for endogenous ET‐1 in the genesis of ischemic arrhythmia in this rat heart model of arrhythmia. Drug Dev. Res. 58:138–144, 2003. © 2003 Wiley‐Liss, Inc.