Treatment with levosimendan in an experimental model of early ventilator-induced diaphragmatic dysfunction


  • Vanessa Zambelli School of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy
  • Emma J. Murphy LIFE – Health and Bioscience Research Institute, Midwest Campus, Technological University of the Shannon, Limerick - Ireland
  • Paolo Del Vecchio School of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy
  • Laura Rizzi School of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy
  • Roberto Fumagalli School of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy and Department of Emergency Medicine, ASST Grande Ospedale Metropolitano Niguarda, Milan - Italy
  • Emanuele Rezoagli School of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy and Department of Emergency and Intensive Care, Fondazione IRCCS San Gerardo dei Tintori, Monza - Italy
  • Giacomo Bellani School of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy and Department of Emergency and Intensive Care, Fondazione IRCCS San Gerardo dei Tintori, Monza - Italy



Diaphragm contractility, Levosimendan, Mechanical ventilation, Muscle fiber size, Ventilator-induced diaphragmatic dysfunction


Introduction: Mechanical ventilation (MV) is a life-saving approach in critically ill patients. However, it may affect the diaphragmatic structure and function, beyond the lungs. Levosimendan is a calcium sensitizer widely used in clinics to improve cardiac contractility in acute heart failure patients. In vitro studies have demonstrated that levosimendan increased force-generating capacity of the diaphragm in chronic obstructive pulmonary disease patients. Thus the aim of this study was to evaluate the effects of levosimendan administration in an animal model of ventilator-induced diaphragmatic dysfunction (VIDD) on muscle contraction and diaphragm muscle cell viability.

Methods: Sprague-Dawley rats underwent prolonged MV (5 hours). VIDD+Levo group received a starting bolus of levosimendan immediately after intratracheal intubation and then an intravenous infusion of levosimendan throughout the study. Diaphragms were collected for ex vivo contractility measurement (with electric stimulation), histological analysis and Western blot analysis. Healthy rats were used as the control.

Results: Levosimendan treatment maintained an adequate mean arterial pressure during the entire experimental protocol, preserved levels of autophagy-related proteins (LC3BI and LC3BII) and the muscular cell diameter demonstrated by histological analysis. Levosimendan did not affect the diaphragmatic contraction or the levels of proteins involved in the protein degradation (atrogin).

Conclusions: Our data suggest that levosimendan preserves muscular cell structure (cross-sectional area) and muscle autophagy after 5 hours of MV in a rat model of VIDD. However, levosimendan did not improve diaphragm contractile efficiency.


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How to Cite

Zambelli, V., Murphy, E. J., Del Vecchio, P., Rizzi, L., Fumagalli, R., Rezoagli, E., & Bellani, G. (2023). Treatment with levosimendan in an experimental model of early ventilator-induced diaphragmatic dysfunction. Drug Target Insights, 17(1), 39–44.



Original Research Article
Received 2023-02-11
Accepted 2023-03-29
Published 2023-04-13