超选择性β1受体阻滞剂兰地洛尔在急性心力衰竭中增强内源性和外源性儿茶酚胺的肌力

Thomas J. Feuerstein, G. Krumpl
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引用次数: 2

摘要

β 1 -肾上腺素受体(β 1 -AR)阻滞剂是治疗慢性左心室功能障碍的一种既定疗法。然而,在急性情况下,左心衰患者的用药是有争议的,特别是潜在的负性肌力作用和应用的肌力药物的拮抗作用可能会使患者的临床情况恶化。最近,超选择性短效β 1 -AR兰地洛尔被用于急性左心室失代偿患者,并与肌力药物联合使用,不仅没有恶化患者的心血管状况,反而改善了患者的心血管状况。本研究总结了β 1 -AR阻滞剂在急性心力衰竭患者中与肌力药物联合作用的理论。具体来说,在受体结合模型中,β 1 -AR阻滞剂兰地洛尔可以诱导正性肌力反应。这些模型是基于这样一个事实,即在左心室功能障碍患者中,儿茶酚胺的血浆水平超过其解离常数,而不是减少而不是改善肌力反应,这是由于占据受体二聚体的负协同作用。兰地洛尔的低浓度降低了负性合作,使受体反应曲线向正性正性范围移动。因此,这篇文章可能有助于减少使用超选择性受体阻滞剂兰地洛尔和正性肌力药物治疗急性左心室恶化的保留意见。更重要的是,在这些模型中计算的兰地洛尔的剂量范围和在重症监护环境中使用的剂量范围是相同的。
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The Superselective β1-Blocker Landiolol Enhances Inotropy of Endogenous and Exogenous Catecholamines in Acute Heart Failure
β 1 -Adrenoceptors (β 1 -AR) blocker are an established therapy for the treatment of chronic left ventricular dysfunction. In the acute setting, however, the administration in patients with left ventricular failure is seen controversial, specifically as a potential negative inotropic effect and antagonism of the applied inotropic agents may possibly worsen the clinical situation of the patient. Recently the super selective short acting β 1 -AR Landiolol has been used in patients with acute left ventricular decompensation and, in conjunction with inotropic agents, did not deteriorate but improved the cardiovascular status of the patients. The present work summarizes the theories how a β 1 -AR blocker may act additive to inotropic agents in patients with acute cardiac failure. Specifically , receptor bindings models are presented in which the β 1 -AR blocker Landiolol can induce a positive inotropic response. These models are based on the fact that in patients with left ventricular dysfunction the plasma levels of catecholamines exceed their dissociation constants and rather decrease than improve the inotropic response due to negative cooperativity at the occupied receptor dimers. Low distinct Landiolol concentrations then reduce the negative cooperation and shift the receptor response curve into a more positive inotropic range. This article may thus help to minimise the reservations to the treatment of acute left ventricular deterioration with the super selective beta blocker Landiolol and positive inotropic agents. More so as the dose range calculated for Landiolol in these models and the one’s used in the intensive care setting prove to be identical.
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