Levosimendan enhances force generation of diaphragm muscle from patients with chronic obstructive pulmonary disease

H. W H Van Hees, P. N R Dekhuijzen, L. M A Heunks

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 μM 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.

Original languageEnglish
Pages (from-to)41-47
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume179
Issue number1
DOIs
Publication statusPublished - 1 Jan 2009

Cite this

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title = "Levosimendan enhances force generation of diaphragm muscle from patients with chronic obstructive pulmonary disease",
abstract = "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 μM 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.",
keywords = "Calcium sensitization, Chronic obstructive pulmonary disease, Diaphragm, Levosimendan",
author = "{Van Hees}, {H. W H} and Dekhuijzen, {P. N R} and Heunks, {L. M A}",
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Levosimendan enhances force generation of diaphragm muscle from patients with chronic obstructive pulmonary disease. / Van Hees, H. W H; Dekhuijzen, P. N R; Heunks, L. M A.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 179, No. 1, 01.01.2009, p. 41-47.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Levosimendan enhances force generation of diaphragm muscle from patients with chronic obstructive pulmonary disease

AU - Van Hees, H. W H

AU - Dekhuijzen, P. N R

AU - Heunks, L. M A

PY - 2009/1/1

Y1 - 2009/1/1

N2 - 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 μM 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.

AB - 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 μM 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.

KW - Calcium sensitization

KW - Chronic obstructive pulmonary disease

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