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Updated: May 28, 2026

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
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The calcium sensitizer levosimendan improves human diaphragm function.

Jonne Doorduin1, Christer A Sinderby, Jennifer Beck

  • 1Radboud University Nijmegen Medical Centre, Department of Critical Care Medicine, Geert Grooteplein zuid 10, 6525 GA Nijmegen, The Netherlands.

American Journal of Respiratory and Critical Care Medicine
|October 1, 2011
PubMed
Summary

Levosimendan improves diaphragm function by enhancing neuromechanical efficiency and preventing contractile loss during loaded breathing. This calcium sensitizer offers a potential new treatment for respiratory muscle weakness.

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Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
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Area of Science:

  • Cardiovascular Pharmacology
  • Respiratory Physiology
  • Muscle Biology

Background:

  • Acquired diaphragm weakness is common in chronic diseases like COPD and heart failure.
  • Current treatments lack drugs to improve respiratory muscle function.
  • Levosimendan, a calcium sensitizer, previously enhanced isolated diaphragm fiber force.

Purpose of the Study:

  • To evaluate the in vivo effects of levosimendan on human diaphragm function.
  • To assess levosimendan's impact on diaphragm contractility and neuromechanical efficiency.

Main Methods:

  • Double-blind, randomized, crossover study with 30 healthy subjects.
  • Levosimendan or placebo administered after inspiratory loading.
  • Measured transdiaphragmatic pressure, diaphragm electrical activity, and neuromechanical efficiency.
  • Assessed twitch contractility and muscle fiber conduction velocity via magnetic phrenic nerve stimulation.

Main Results:

  • Levosimendan prevented the 9% loss of diaphragm twitch contractility seen in the placebo group.
  • Diaphragm neuromechanical efficiency improved by 21% with levosimendan.
  • Baseline diaphragm electrical activity center frequency decreased post-levosimendan.

Conclusions:

  • Levosimendan enhances human diaphragm neuromechanical efficiency and contractile function.
  • This suggests levosimendan as a novel therapeutic strategy for respiratory failure.
  • Improves respiratory muscle function in patients with diaphragm weakness.