Landiolol has a less potent negative inotropic effect than esmolol in isolated rabbit hearts
Landiolol has a less potent negative inotropic effect than esmolol in isolated rabbit hearts
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DOI：
10.1007/s00540-008-0640-4
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发表时间：
2008-11-01
影响因子：
2.8
通讯作者：
Asada, Akira
中科院分区：
文献类型：
--
作者：
Ikeshita, Kazutoshi;Nishikawa, Kiyonobu;Asada, Akira
我们使用完整的离体兔心脏制剂，比较了兰地洛尔和艾司洛尔这两种临床上可用的具有高β1选择性的短效β1受体阻滞剂的负变时性和正性肌力作用。通过连续灌注10(-7)M异丙肾上腺素诱导心动过速，并且我们以递增的步骤使用兰地洛尔或艾司洛尔的浓度（1中心点10(-6)，3中心点 10(-6)、1 个中心点 10(-5)、3 个中心点 10(-5) 和 1 个中心点 10(-4) M)。测量并比较心率（HR）、左心室发展压（LVDP）、左心室发展力最大速率（LVdP/dt（max））和心肌耗氧量（MVO2）。兰地洛尔和艾司洛尔均产生HR、LVDP、LVdP/dt（max）和MVO2的剂量依赖性降低。两种药物的 HR 降低效果相当。在3个中心点10(-5)和1个中心点10(-4)M浓度下，艾司洛尔产生更严重的LVDP抑制（分别为47+/-26和12+/-11mmHg；平均值+/-SD）和LVdP/dt（最大值）的降低（650+/-287和120+/-103mmHg中心点s(-1)）比兰地洛尔（分别为 68 +/- 20 和 64 +/- 20 mmHg，以及 897 +/- 236 和 852 +/- 240 mmHg 中心点 s(-1)）。在相同浓度下，艾司洛尔分别比兰地洛尔（50+/-8和48+/-8μl中心点分钟（-1）中心点g（-1））引起MVO2更显着的降低（40+/-11和35+/-10μl中心点分钟（-1）中心点g（-1））。我们的结果表明，在离体兔心脏中，兰地洛尔和艾司洛尔具有等价性负性变时作用，然而，兰地洛尔的负性肌力作用不如艾司洛尔强。
We compared the negative chronotropic and inotropic effects of landiolol and esmolol, two clinically available short-acting beta 1-blockers with high beta 1-selectivity, using whole isolated rabbit heart preparations.Tachycardia was induced by continuous perfusion of 10(-7) M isoproterenol, and we used concentrations of landiolol or esmolol in ascending steps (1 center dot 10(-6), 3 center dot 10(-6), 1 center dot 10(-5), 3 center dot 10(-5), and 1 center dot 10(-4) M). Heart rate (HR), left ventricular developed pressure (LVDP), the maximal rates of left ventricular force development (LVdP/dt(max)), and myocardial oxygen consumption (MVO2) were measured and compared.Both landiolol and esmolol produced dosedependent decreases in HR, LVDP, LVdP/dt(max), and MVO2. The HR lowering effects of the two agents were comparable. At concentrations of 3 center dot 10(-5) and 1 center dot 10(-4) M, esmolol produced more profound depression of LVDP (47 +/- 26 and 12 +/- 11 mmHg, respectively; mean +/- SD) and reduction of LVdP/dt(max) (650 +/- 287 and 120 +/- 103 mmHg center dot s(-1)) than landiolol (68 +/- 20 and 64 +/- 20 mmHg, and 897 +/- 236 and 852 +/- 240 mmHg center dot s(-1), respectively). At the same concentrations, esmolol caused more profound reduction in MVO2 (40 +/- 11 and 35 +/- 10 mu l center dot min(-1) center dot g(-1)) than landiolol (50 +/- 8 and 48 +/- 8 mu l center dot min(-1) center dot g(-1)), respectively.Our results indicate that in the isolated rabbit heart, landiolol and esmolol had equipotent negative chronotropic effects, however, landiolol had a less potent negative inotropic effect than esmolol.