Weakened diaphragm contraction in the septic rats was associated with reduced mRNA and protein expression of DHPRα1s and RyR1, the isoforms of skeletal muscles.

New Findings r What is the central question of this study?Higher levels of positive end-expiratory pressure (PEEP) have recently been used in patients with acute respiratory distress syndrome (ARDS). In normal physiological conditions, the ability of the diaphragm to generate pressure is reduced when the lung volume is elevated beyond its functional residual capacity. It is unknown whether higher levels of PEEP will have a negative impact on diaphragmatic contraction in the presence of the pathophysiology of ARDS. r What is the main finding and its importance?Mechanical ventilation with higher levels of PEEP reduced lung injury, improved diaphragmatic contractility and increased the expression of both dihydropyridine receptor and ryanodine receptor in the diaphragms of rats with ARDS.Higher levels of positive end-expiratory pressure (PEEP) have recently been used in patients with acute respiratory distress syndrome (ARDS). In normal physiological conditions, the ability of the diaphragm to generate pressure is reduced when the lung volume is elevated beyond its functional residual capacity. Thus, it is critical to understand whether higher levels of PEEP will have a negative impact on diaphragmatic contraction in the presence of the pathophysiology of ARDS. This study was designed to determine whether higher levels of PEEP reduce diaphragmatic contractility in a rat model of ARDS generated using i.p. lipopolysaccharide. Forty rats were randomly assigned to the following five groups: a control group with no special treatment; an ARDS group with no mechanical ventilation; and three ARDS groups with mechanical ventilation with PEEP at 0, 5 or 10 cmH 2 O, respectively. We found that mechanical ventilation with PEEP reduced lung injury, improved diaphragmatic contractility and increased the expression of both dihydropyridine receptor and ryanodine receptor in the diaphragms of rats with ARDS. These changes were most significant at a PEEP of 10 cmH 2 O among all applied levels of PEEP. In conclusion, using a rat ARDS model, this study confirmed that diaphragmatic contractility was preserved by mechanical ventilation with high levels of PEEP.