Comparison of the Effect of the ATP-Sensitive Potassium Channel Opener YM934 With That of Nitroglycerin on Impaired Coronary Circulation in Dogs
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概要
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We compared the effect of an ATP-sensitive potassium channel opener, YM934, with that of nitroglycerin (NTG) on impaired coronary circulation in dogs. Coronary stenosis was produced in 7 dogs by placing a hydraulic occluder around the proximal left circumflex coronary (LCx) artery and abolishing reactive hyperemia to compromise the LCx flow. The following parameters were measured: the aortic pressure, LCx flow velocity, LCx vessel diameter, LCx peripheral pressure, and segment length in the LCx area. Subsequently, we occluded the LCx artery for 15 seconds and measured the recovery-interval (time required for the segment shortening to return to the preocclusion value). The measurements were recorded under three study conditions: (1) at baseline without LCx stenosis; (2) with LCx stenosis under NTG infusion (3 μg/Kg/min); and (3) with LCx stenosis after intravenous administration of YM934 (0.3 μg/kg). The heart rate and aortic pressure were similar under the three study conditions. Mean LCx flow velocity and segment shortening did not significantly change either. However, LCx peripheral pressure decreased after the induction of stenosis (P < 0.05) and showed no response to either NTG or YM934. YM934 administration significantly increased LCx flow in the presence of LCx stenosis, (P < 0.05), whereas NTG infusion did not. YM934 significantly shortened the recovery-interval of the segment shortening after 15-sec LCx occlusion (P < 0.05), whereas NTG did not. These findings suggest that YM934 improves coronary blood flow and prevents myocardial ischemic damage in severely impaired coronary circulation.
著者
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Yamaguchi Iwao
Cardiology Department Of Internal Medicine University Of Tsukuba Graduate School Of Comprehensive Hu
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Ishikawa Kimito
Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University
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Masuda Noriyuki
Pharmacology Research Laboratories Institute For Drug Discovery Research Astellas Pharmaceutical Inc
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Ohtsuka Sadanori
Cardiovascular Division Department Of Internal Medicine Institute Of Clinical Medicine University Of
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Uchida Wataru
Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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Ishikawa Kimito
Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba
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Suzuki Shoji
Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba
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Masuda Noriyuki
Pharmacology Research Laboratories, Institute for Drug Discovery Research, Astellas Pharmaceutical Inc., Ibaraki
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