Different responses of epicardium and endocardium to KATP channel modulators during regional ischemia.
We examined the responses of epicardial (Epi) and endocardial (Endo) layers to ATP-sensitive K+ (KATP) channel modulators during regional ischemia in anesthetized dogs. Five-minute occlusion of the left anterior descending coronary artery was repeated at 30-min interval. Monophasic action potentials (MAPs) and extracellular K+ concentrations ([K+]o) were measured at Epi and Endo layers. 5-Hydroxydecanoate (5-HD, 30 mg/kg iv), a KATP channel blocker, or nicorandil (NCR, 0.2-0.5 mg/kg iv), an opener, was administered before the third or fourth occlusion. Shortening rate of action potential duration at 90% repolarization (APD90) was greater at the Epi layer than at the Endo layer during the first 4 min after the second control occlusion (19.7 +/- 1.5 vs. 13.1 +/- 2.4%, n = 14, P < 0.05). 5-HD suppressed the shortening preferentially at the Epi layer and reduced the difference between the two layers (11.0 +/- 3.5 vs. 11.5 +/- 3.7%, n = 6, NS). In contrast, NCR augmented the shortening preferentially at the Epi layer and increased the difference between the two layers at 4 min (29.0 +/- 2.0 vs. 5.9 +/- 3.0%, n = 6, P < 0.05). The time differentiation of [K+]o rise was similar at the two layers during the control occlusion (0.44 vs. 0.50 mM/min, n = 12). 5-HD reduced the rate of [K+]o rise at both layers (0.34 vs. 0.40 mM/min), whereas NCR augmented the rate at the Epi layer (0.82 vs. 0.50 mM/min). Activation of KATP channels appears to be involved in ischemia-induced APD shortening and [K+]o rise. The different responses of the two layers suggest a lower threshold for activation and/or a denser distribution of KATP channels or other K+ channels at the Epi layer.
Miyoshi
S
S
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Miyazaki
T
T
Moritani
K
K
Ogawa
S
S
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology; D004285:Dogs; D004699:Endocardium / Q000187:drug effects / Q000503:physiopathology*; D006880:Hydroxy Acids / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil; D009994:Osmolar Concentration; D010496:Pericardium / Q000187:drug effects / Q000503:physiopathology*; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011930:Reaction Time / Q000187:drug effects
D003652:Decanoic Acids; D006880:Hydroxy Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D009536:Niacinamide; D020108:Nicorandil; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D011188:Potassium