Blockade of ATP-sensitive potassium channels by 5-hydroxydecanoate suppresses monophasic action potential shortening during regional myocardial ischemia.
We tested 5-hydroxydecanoate (5-HD), a specific blocker of ATP-sensitive potassium channels (IK.ATP), to determine if mitigates electrophysiologic changes produced by regional myocardial ischemia in vivo. A sequence of 5-minute occlusion of the distal LAD and 30-minute reperfusion was repeated while recording the monophasic action potential (MAP) and bipolar electrogram (EG) from the epicardial center of the ischemic myocardium in anesthetized dogs. 5-HD (30 mg/kg, i.v.) or glibenclamide (0.15 or 0.3 mg/kg, i.v.) was administered before the third occlusion, and the data were compared to the second occlusion data. 5-HD did not affect baseline MAP duration at 90% and 50% repolarization (APD90, APD50) before LAD occlusion but suppressed occlusion-induced shortening of APD90 (16 +/- 2% during the second occlusion vs. 5 +/- 3% during the third occlusion, n = 8, p < 0.01) and APD50 (16 +/- 3% vs. 10 +/- 3%, n = 8, p < 0.05). Pretreatment with glibenclamide also suppressed occlusion-induced MAP shortening and eliminated an additional effect of 5-HD (n = 3). 5-HD did not affect the occlusion-induced increase in duration and activation time of EG. 5-HD, as well as glibenclamide, suppressed regional ischemia-induced MAP shortening, probably by blocking activation of IK.ATP, without affecting conduction delay. These differential effects of 5-HD on repolarization and conduction during the early phase of regional ischemia might have the potential to suppress reentrant ventricular arrhythmias.
Moritani
K
K
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Miyazaki
T
T
Miyoshi
S
S
Asanagi
M
M
Zhao
L S
LS
Mitamura
H
H
Ogawa
S
S
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003652:Decanoic Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004285:Dogs; D004594:Electrophysiology; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D006880:Hydroxy Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy; D015221:Potassium Channels / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D005905:Glyburide