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决奈达隆和胺碘酮对大鼠离体心脏血浆甲状腺激素及基础和缺血后性能的影响。

Effects of dronedarone and amiodarone on plasma thyroid hormones and on the basal and postischemic performance of the isolated rat heart.

作者信息

Pantos Constantinos, Mourouzis Iordanis, Delbruyère Martine, Malliopoulou Vassiliki, Tzeis Stylianos, Cokkinos Demosthenis D, Nikitas Nikos, Carageorgiou Hariclia, Varonos Dennis, Cokkinos Dennis, Nisato Dino

机构信息

Department of Pharmacology, University of Athens, 75 Mikras Asias Ave., 11527 Goudi, Greece.

出版信息

Eur J Pharmacol. 2002 May 31;444(3):191-6. doi: 10.1016/s0014-2999(02)01624-2.

Abstract

The present study investigated the effects of dronedarone and amiodarone on plasma thyroid hormones and the possible consequences on the response of the heart to ischemia. Amiodarone (30 mg/kg/day per os) or dronedarone (30 mg/kg/day per os) were administered for 2 weeks in normal and thyroxine-treated animals (25 microg/100 g body weight od sc, for 2 weeks), while animals without amiodarone and dronedarone served as controls. Isolated rat hearts were perfused in a Langendorff mode and subjected to 20 and 30 min of zero-flow global ischemia followed by 45 min of reperfusion. Functional changes were assessed by measuring left ventricular developed pressure (LVDP) under resting conditions and in response to ischemia-reperfusion, LVDP%, as well as the severity of ischemic contracture. Amiodarone resulted in increased T4, T4/T3 and rT3, whereas dronedarone did not alter the thyroid hormone profile in normal animals. In thyroxine-treated animals, amiodarone increased T4/T3 ratio but T4, T3 and rT3 levels were not altered. Basal functional parameters and ischemic contracture did not change by amiodarone and/or dronedarone neither in normal nor in thyroxine-treated hearts. In normal hearts, postischemic functional recovery, LVDP%, was not altered by amiodarone or dronedarone administration. LVDP% was statistically higher in thyroxine-treated hearts than in normal and this beneficial effect was not abolished by amiodarone or dronedarone treatment.

摘要

本研究调查了决奈达隆和胺碘酮对血浆甲状腺激素的影响以及对心脏缺血反应可能产生的后果。在正常动物和经甲状腺素治疗的动物(皮下注射25μg/100g体重,持续2周)中,给予胺碘酮(30mg/kg/天,口服)或决奈达隆(30mg/kg/天,口服)2周,而未给予胺碘酮和决奈达隆的动物作为对照。将离体大鼠心脏以Langendorff模式灌注,使其经历20分钟和30分钟的零流量全心缺血,随后再灌注45分钟。通过测量静息状态下以及缺血再灌注后的左心室舒张末压(LVDP)、LVDP%以及缺血性挛缩的严重程度来评估功能变化。胺碘酮导致T4、T4/T3和反T3升高,而决奈达隆在正常动物中未改变甲状腺激素水平。在经甲状腺素治疗的动物中,胺碘酮增加了T4/T3比值,但T4、T3和反T3水平未改变。在正常心脏和经甲状腺素治疗的心脏中,胺碘酮和/或决奈达隆均未改变基础功能参数和缺血性挛缩。在正常心脏中,给予胺碘酮或决奈达隆后,缺血后功能恢复、LVDP%未改变。经甲状腺素治疗的心脏中的LVDP%在统计学上高于正常心脏,且这种有益作用未被胺碘酮或决奈达隆治疗消除。

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