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首页> 外文期刊>American Journal of Physiology >Effects of incremental beta-blocker dosing on myocardial mechanics of the human left ventricle: MRI 3D-tagging insight into pharmacodynamics supports theory of inner antagonism
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Effects of incremental beta-blocker dosing on myocardial mechanics of the human left ventricle: MRI 3D-tagging insight into pharmacodynamics supports theory of inner antagonism

机译：增量β阻滞剂给药对人类左心室心肌机制的影响：MRI 3D标记洞察洞察药物动力学支持内部对抗理论

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Beta-blockers contribute to treatment of heart failure. Their mechanism of action, however, is incompletely understood. Gradients in beta-blocker sensitivity of helically aligned cardiomyocytes compared with counteracting transversely intruding cardiomyocytes seem crucial. We hypothesize that selective blockade of transversely intruding cardiomyocytes by low-dose beta-blockade unloads ventricular performance. Cardiac magnetic resonance imaging (MRI) 3D tagging delivers parameters of myocardial performance. We studied 13 healthy volunteers by MRI 3D tagging during escalated intravenous administration of esmolol. The circumferential, longitudinal, and radial myocardial shortening was determined for each dose. The curves were analyzed for peak value, time-to-peak, upslope, and area-under-the-curve. At low doses, from 5 to 25 mug·kg~(-1)·min~(-1), peak contraction increased while time-to-peak decreased yielding a steeper upslope. Combining the values revealed a left shift of the curves at low doses compared with baseline without esmolol. At doses of 50 to 150 mug·kg~(-1)·min~(-1), a right shift with flattening occurred. In healthy volunteers we found more pronounced myocardial shortening at low compared with clinical dosage of beta-blockers. In patients with ventricular hypertrophy and higher prevalence of transversely intruding cardiomyocytes selective low-dose beta-blockade could be even more effective. MRI 3D tagging could help to determine optimal individual beta-blocker dosing avoiding undesirable side effects.
机译：β-阻滞剂有助于治疗心力衰竭。然而，他们的行动机制是不完全理解的。与抵抗横向侵入的心肌细胞相比，β-阻滞剂敏感性的梯度对齐的心肌细胞似乎至关重要。我们假设通过低剂量β-嵌入卸载心室性能的横向侵入心肌细胞的选择性阻断。心脏磁共振成像（MRI）3D标记提供了心肌性能的参数。我们通过升级静脉施用Esmolol期间通过MRI 3D标记研究了13个健康的志愿者。针对每种剂量测定圆周，纵向和径向心肌缩短。分析曲线以进行峰值，峰值，上坡和曲线下的曲线。在低剂量，从5到25杯·kg〜（-1）·min〜（-1），峰值收缩增加，而峰值降低，产生陡峭的上坡。组合这些值显示在低剂量下曲线与没有Esmolol的基线相比的左转。剂量为50至150杯·kg〜（-1）·min〜（-1），发生扁平化的右转。在健康的志愿者中，与β-oplaters的临床剂量相比，我们发现更明显的心肌缩短。在患有心室肥大和横向侵入心肌细胞的患者的患者中，选择性低剂量β-阻滞可能更有效。 MRI 3D标记可以帮助确定最佳的个体β阻滞剂给药避免不期望的副作用。

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