Different sensitivity of the epicardial and endocardial layers to k.atp channel modulators during regional myocardial ischemia. Miyoshi, Shunichiro, Toshihisa Miyazaki, Kazunori Moritani, Satoshi Ogawa. Cardiopulmonary Division, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160, Japan
APStracts 2:0560H, 1995.
Purpose: We tested whether there might be a difference in the responses of epicardial (Epi) and endocardial (Endo) layers to ATP -sensitive potassium (K.ATP) channel modulators during regional ischemia in anesthetized, open-chest dogs. Methods: A sequence of 5 -minute occlusion of the distal LAD and 30-minute reperfusion was repeated. At the center of ischemic zone, Epi and Endo monophasic action potentials (MAPs) were recorded simultaneously and extracellular potassium concentrations ([K+]o) were measured using valinomycin electrodes. 5-hydroxydecanoate (30 mg/kg; 5-HD), a specific blocker of K.ATP channels or nicorandil (0.2-0.5 mg/kg; NCR), an opener was administered intravenously before the third or fourth occlusion, then the data were compared to the second (control) occlusion data. Results: Shortening rate of MAP duration at 90% repolarization (APD90) was greater at Epi than at Endo layer during the first 4 minutes after the control occlusion (19.7 +/- 1.5 vs. 13.1 +/- 2.4 %, n=14, p&LT0.05). Pretreatment with 5-HD suppressed occlusion-induced shortening of APD90 preferentially at Epi layer, and reduced the difference between the two layers at 4 minutes(11.0 +/- 3.5 vs. 11.5 +/- 3.7%, n=6, NS). In contrast NCR augmented the occlusion-induced shortening preferentially at Epi layer, and increased the difference between the two layers at 4 minutes ( 29.0 +/- 2.0 vs. 5.9 +/- 3.0 %, n=6, p&LT0.05). The time differentiation of [K+]o rise was similar at Epi and Endo layers during the control occlusion (0.44 vs. 0.50 mM/min, n=12). Pretreatment with 5-HD reduced the rate of [K+]o rise at both layers (0.34 vs. 0.40 mM/min), whereas NCR augmented the rate preferentially at Epi layer (0.82 vs. 0.50 mM/min). Collateral blood flow measured using radioactive microspheres during the control occlusion was greater at Epi than Endo layer (31.3 +/- 12.5 vs. 8.9 +/- 3.1 ml/100g/min, n=8, p&LT0.05). Conclusion: These data suggest that activation of K.ATP channels contributes to regional ischemia-induced APD shortening and [K+]o rise, and produces an electrical difference between the epicardial and endocardial layers. The K.ATP channel modulators appear to affect the epicardial layer preferentially in spite of the fact that the extent of ischemia is less severe in the epicardial layer than in the endocardial layer. The different sensitivity to the drugs might be explained by a lower threshold for activation and/or a denser distribution of K.ATP channels or other potassium channels at the epicardial layer. 

Received 5 December 1994; accepted in final form 5 December 1995.
APS Manuscript Number H1063-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95