Levosimendan Enhances Force Generation of Diaphragm Muscle from Patients with Chronic Obstructive Pulmonary Disease
Levosimendan Enhances Force Generation of Diaphragm Muscle from Patients with Chronic Obstructive Pulmonary Disease
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DOI：
10.1164/rccm.200805-732oc
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发表时间：
2009-01-01
影响因子：
24.7
通讯作者：
Heunks, Leo M. A.
中科院分区：
文献类型：
--
作者：
van Hees, Hieronymus W. H.;Dekhuijzen, P. N. Richard;Heunks, Leo M. A.
理论基础左西孟丹在临床上用于通过增强力产生的钙敏感性来改善心肌收缩能力。左西孟丹对骨骼肌收缩力的影响尚不清楚。目的：探讨左西孟旦对慢性阻塞性肺疾病(COPD)患者横隔肌纤维收缩性能的影响。方法：从5例COPD患者和5例非COPD开胸术患者(每例均为10个肌纤维)的横隔膜活检标本中分离肌纤维。用含有递增钙浓度和10亩M左西孟丹或赋形剂(0.02%二甲基亚砜)的溶液对隔膜纤维进行剥离和激活。在每一步测量发展的力，并推导出力与钙浓度的关系。结果按肌球蛋白重链亚型分组，经十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)测定。测量和主要结果：在亚最大激活时，左西孟丹使慢纤维和快纤维中COPD和非COPD横隔纤维的作用力增加约25%。结论：左西孟丹通过增加慢性阻塞性肺疾病患者和非慢性阻塞性肺疾病患者的横隔肌纤维的钙离子敏感性，提高了慢、快肌纤维的力生成能力(P<；0.01)，而不影响最大力生成。这些结果为测试钙增敏剂对COPD患者呼吸肌功能障碍的影响提供了强有力的理论依据。
Rationale Levosimendan is clinically used to improve myocardial contractility by enhancing calcium sensitivity of force generation. The effects of levosimendan on skeletal muscle contractility are unknown. Patients with chronic obstructive pulmonary disease (COPD) suffer from diaphragm weakness, which is associated with decreased calcium sensitivity.Objectives: To investigate the effects of levosimendan on contractility of diaphragm fibers from patients with COPD.Methods: Muscle fibers were isolated from diaphragm biopsies obtained from thoracotomized patients with and without COPD (both groups n = 5, 10 fibers per patient). Diaphragm fibers were skinned and activated with solutions containing incremental calcium concentrations and 10 mu M levosimendan or vehicle (0.02% dimethyl sulfoxide). Developed force was measured at each step and force versus calcium concentration relationships were derived. Results were grouped per myosin heavy chain isoform, which was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).Measurements and Main Results: At sub-maximal activation levosimendan improved force generation of COPD and non-COPD diaphragm fibers by approximately 25%, both in slow and fast fibers. Levosimendan increased calcium sensitivity of force generation (P < 0.01) in both slow and fast diaphragm fibers from patients with and without COPD, without affecting maximal force generation.Conclusions: Levosimendan enhances force generating capacity of diaphragm fibers from patients with and without COPD patients by increasing calcium sensitivity of force generation. These results provide a strong rationale for testing the effect of calcium sensitizers on respiratory muscle dysfunction in patients with COPD.