caa a22 4500 475833465 CHVBK 20180406123847.0 cr unu---uuuuu 170329e20000301xx s 000 0 eng 10.1023/A:1007830607733 doi (NATIONALLICENCE)springer-10.1023/A:1007830607733 Attenuation of KATP Channel-Opener Induced Shortening of Repolarization Time by α1-Adrenoceptor Antagonist During Ischemia in Canine Heart [Elektronische Daten] [Teruhisa Tanabe, Minoru Aikawa, Yoshiaki Deguchi, Koichiro Yoshioka, Shunnosuke Handa] The purpose of the study was to determine whether a newKATP channel opener, Y 26763 (Y), can influence theelectrophysiological properties in the ischemic myocardium as well as todetermine whether the blunting effect of the α1-adrenoceptorantagonist bunazosin (BN) on an ischemia-induced shortening of repolarizationtime can be related to the KATP channel activity. The anteriordescending branch of the left coronary artery was ligated four times for 5minutes, separated by 15 minutes of reperfusion (stages 1-4) to testthe dose-dependent effect of drugs on repolarization. Dogs received eithervehicle (n = 9), Y (0.4, 2.0, and 4.0 μg/kg at stages 2, 3, and 4,respectively, with 0.4 μg/kg/min drip infusion at each of stages2-4, n = 7), BN (0.1 mg at each of stages 2-4, n =8), or a combination of these two drugs (BN + Y, the same dose of BNand Y in groups BN and Y, respectively, n = 9). Drugs wereadministered into the left atrium. The monophasic action potential (MAP)and regional electrograms were recorded. The MAP90 and theduration of the slow deflections (DSD) of the regional electrogram were usedas markers of repolarization. The Vmax of the MAP and the rapiddeflections (DRD) of the regional electrogram were used as markers ofconduction. Y augmented an ischemia-induced shortening of MAP90and DSD in proportion to an increase in the dose given and the plasmaconcentration (P < .05-.01), especially at the epicardialsite. BN and BN + Y blunted the ischemia-related shortening ofMAP90 and DSD, causing a reduction in repolarization timedispersion between the ischemic and normal zones. There were no significantchanges in the Vmax or DRD in the ischemic zone between periodsbefore and after an increase in each drug dose in the four groups. None ofthe seven dogs developed ventricular tachycardia (VT)/ventricularfibrillation (VF) in the Y group, whereas two of the eight dogs in theBN group, three of the nine dogs in the BN + Y group, and three ofthe nine dogs in the control group developed VT/VF. These results suggestthat the α1-adrenergic blocker bunazosin blunts theshortening effect of KATP channel activator on repolarizationtime, and that the KATP channel opener Y may be antiarrhythmic,although the repolarization time dispersion during myocardial ischemia isincreased. Kluwer Academic Publishers, 2000 dogs nationallicence KATP channel opener nationallicence Y-26763 nationallicence alpha1-antagonist nationallicence Y effects nationallicence bunazosin nationallicence ischemia nationallicence endocardium nationallicence epicardium nationallicence Tanabe Teruhisa Department of Cardiovascular Medicine, School of Medicine, Tokai University, Isehara, Japan aut Aikawa Minoru Department of Cardiovascular Medicine, School of Medicine, Tokai University, Isehara, Japan aut Deguchi Yoshiaki Department of Cardiovascular Medicine, School of Medicine, Tokai University, Isehara, Japan aut Yoshioka Koichiro Department of Cardiovascular Medicine, School of Medicine, Tokai University, Isehara, Japan aut Handa Shunnosuke Department of Cardiovascular Medicine, School of Medicine, Tokai University, Isehara, Japan aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/3(2000-03-01), 283-294 0920-3206 14:3<283 2000 14 10557 https://doi.org/10.1023/A:1007830607733 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1007830607733 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tanabe Teruhisa Department of Cardiovascular Medicine, School of Medicine, Tokai University, Isehara, Japan aut NATIONALLICENCE 700 1- Aikawa Minoru Department of Cardiovascular Medicine, School of Medicine, Tokai University, Isehara, Japan aut NATIONALLICENCE 700 1- Deguchi Yoshiaki Department of Cardiovascular Medicine, School of Medicine, Tokai University, Isehara, Japan aut NATIONALLICENCE 700 1- Yoshioka Koichiro Department of Cardiovascular Medicine, School of Medicine, Tokai University, Isehara, Japan aut NATIONALLICENCE 700 1- Handa Shunnosuke Department of Cardiovascular Medicine, School of Medicine, Tokai University, Isehara, Japan aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/3(2000-03-01), 283-294 0920-3206 14:3<283 2000 14 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer