Effect of the sarcolemmal K(ATP) channel blocker HMR1098 on arrhythmias induced by programmed electrical stimulation in canine old myocardial infarction model: comparison with glibenclamide.
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.
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D005905:Glyburide / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D026902:Potassium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D015221:Potassium Channels / Q000502:physiology; D012508:Sarcolemma / Q000187:drug effects / Q000502:physiology
D001549:Benzamides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000255:Adenosine Triphosphate; C410297:HMR 1098; D005905:Glyburide