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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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BACKGROUND: Studies are showing that pulmonary rehabilitation (PR) increases diaphragmatic excursion by decreasing hyperinflation in patients with chronic obstructive pulmonary disease (COPD). However, there is a lack of knowledge about its effects on the diaphragm thickness (dt) and contractility. This study aims to evaluate the dt and contractility before and after PR in patients with COPD. METHODS: All subjects participated in an out-patient PR of 6 weeks and 3 sessions per week prospectively. Dyspnea severity, the disease-specific quality of life (St. Georges Respiratory Questionnaire-SGRQ), pulmonary function tests (PFT), exercise capacity, the dt at the end of the expiration and at maximal inspiration (B-mode ultrasound) were evaluated at baseline and after PR. RESULTS: A total of 34 patients with a mean age and FEV1 61.05 ± 8.22 years and 57.9 ± 20.4% predicted respectively showed improvements in exercise capacity and some items of PFT and SGRQ. Diaphragmatic thickness at the end of the expiration also significantly improved regardless of the disease severity and was positively correlated with functional performance. The 6-weeks of PR didn't result in a significant difference in diaphragm contractility.

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BACKGROUND: This study assessed the effects of a new interface that combined CPAP 10 cm H2O by using a helmet with high-flow nasal cannula (HFNC) at varying flows in healthy volunteers. Outcome measures included pharyngeal pressures, diaphragm kinetics, breathing frequency, the temperature inside the helmet, and comfort. METHODS: After baseline assessment during spontaneous breathing, HFNC was applied at flows of 30, 40, and 50 L/min. Successively, the volunteers underwent helmet CPAP at 10 cm H2O and CPAP + HFNC at flows of 30, 40, and 50 L/min. We measured the variations of pharyngeal pressures at end-expiration and end-inspiration, referenced to spontaneous breathing for HFNC and to CPAP for CPAP + HFNC, diaphragm displacement and thickness at end-expiration and thickness at end-inspiration, breathing frequency, the temperature inside the helmet, the occurrence of the fog effect, and comfort. RESULTS: Variations of pharyngeal pressures at end-inspiration changes were small overall and clinically unimportant. With the mouth closed, at increasing HFNC flow, variations of pharyngeal pressures at end-expiration increased during both HFNC (from 2.8 up to 7.7) and, to a lesser extent, CPAP + HFNC (from 2.7 up to 3.8) (P < .001 for all comparisons). These variations were attenuated during open-mouth breathing. HFNC ≥ 40 L/min and CPAP + HFNC ≥ 40 L/min compared with spontaneous breathing and CPAP, respectively, increased diaphragm displacement (P = .001), thickness at end-inspiration and thickness at end-expiration (P < .003 for both). At all flows, breathing frequency was slightly, although significantly, lower with CPAP + HFNC than with HFNC alone (P < .003). The temperature inside the helmet increased slightly and insignificantly at flows of ≤40 L/min with CPAP + HFNC compared with CPAP alone. The fog effect never occurred, whereas comfort was always rated as optimal, without differences between trials. CONCLUSIONS: CPAP + HFNC was well tolerated, with no adverse effects. Based on our findings, there was no need to vary the CPAP level when adding HFNC. At least in healthy subjects, CPAP + HFNC at 30 L/min seemed to be the best combination.

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The current work was conducted to verify the contribution of neuromuscular transmission defects at the neuromuscular junction to Duchenne Muscular Dystrophy disease progression and respiratory dysfunction. We tested pyridostigmine and pyridostigmine encapsulated in liposomes (liposomal PYR), an acetylcholinesterase inhibitor to improve muscular contraction on respiratory muscle function in mdx mice at different ages. We evaluated in vivo with the whole-body plethysmography, the ventilatory response to hypercapnia, and measured in vitro diaphragm strength in each group. Compared to C57BL10 mice, only 17 and 22 month-old mdx presented blunted ventilatory response, under normocapnia and hypercapnia. Free pyridostigmine (1mg/kg) was toxic to mdx mice, unlike liposomal PYR, which did not show any side effect, confirming that the encapsulation in liposomes is effective in reducing the toxic effects of this drug. Treatment with liposomal PYR, either acute or chronic, did not show any beneficial effect on respiratory function of this DMD experimental model. The encapsulation in liposomes is effective to abolish toxic effects of drugs.

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