In a rat model of ventilator-induced diaphragmatic dysfunction, levosimendan preserved muscular cell structure and prevented autophagy after 5 hours of mechanical ventilation, but did not improve diaphragm contractile efficiency.
Does levosimendan improve diaphragm contractile efficiency and preserve muscular cell structure in a rat model of ventilator-induced diaphragmatic dysfunction?
In a rat model of ventilator-induced diaphragmatic dysfunction, levosimendan preserved muscle fiber size and autophagy markers but failed to improve diaphragm contractile efficiency.
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.
Zambelli et al. (Thu,) conducted a other in Ventilator-induced diaphragmatic dysfunction (n=28). Levosimendan vs. Mechanical ventilation without treatment (VIDD) and healthy spontaneously breathing rats was evaluated on Diaphragm muscular contractile function and cross-sectional area. In a rat model of ventilator-induced diaphragmatic dysfunction, levosimendan preserved muscular cell structure and prevented autophagy after 5 hours of mechanical ventilation, but did not improve diaphragm contractile efficiency.