Key result
HMR1098 significantly improved the scores of programmed electrical stimulation-induced ventricular arrhythmias in a canine old myocardial infarction model (P<0.01), whereas glibenclamide had no significant effect.
Why the study?
Does HMR1098 reduce PES-induced ventricular arrhythmias in a canine old myocardial infarction model?
Does HMR1098 reduce PES-induced ventricular arrhythmias in a canine old myocardial infarction model?
p-value: p=<0.01
The cardioselective KATP channel blocker HMR1098 suppresses PES-induced ventricular arrhythmias in a canine old MI model without affecting blood glucose, unlike the classical sulfonylurea glibenclamide.
Cardioselective K(ATP) blockade remains unproven in post-MI arrhythmias; leaves open translation from canine PES models to patients.
The blockade of myocardial K(ATP) channels may be antiarrhythmic for ischemic arrhythmias. A new sulfonylthiourea, HMR1098 (1-[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenylsulfonyl]-3-methylthiourea, sodium salt), was demonstrated to be a cardioselective K(ATP)-channel antagonist and to suppress arrhythmias during acute ischemia. We investigated effects of HMR1098 on the arrhythmias induced by programmed electrical stimulation (PES) in a canine old myocardial infarction model. HMR1098 (3 mg/kg, i.v.) significantly improved the scores of PES-induced ventricular arrhythmias, without changing the blood glucose concentrations. A classical sulfonylurea, glibenclamide (1 mg/kg, i.v.), had no significant effects on these arrhythmias, but reduced the blood glucose and increased the plasma insulin concentrations.
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Zhu et al. (2003) studied Old myocardial infarction with programmed electrical stimulation-induced arrhythmias (n=24). HMR1098 vs. Saline and Glibenclamide (1 mg/kg i.v.) was evaluated on Severity of PES-induced ventricular arrhythmias (arrhythmia score) (p=<0.01). HMR1098 significantly improved the scores of programmed electrical stimulation-induced ventricular arrhythmias in a canine old myocardial infarction model (P<0.01), whereas glibenclamide had no significant effect.
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