Abstract
IntroductionDiaphragm weakness induced by prolonged mechanical ventilation may contribute to difficult weaning from the ventilator. Hypercapnia is an accepted side effect of low tidal volume mechanical ventilation, but the effects of hypercapnia on respiratory muscle function are largely unknown. The present study investigated the effect of hypercapnia on ventilator-induced diaphragm inflammation, atrophy and function.MethodsMale Wistar rats (n = 10 per group) were unventilated (CON), mechanically ventilated for 18 hours without (MV) or with hypercapnia (MV + H, Fico2 = 0.05). Diaphragm muscle was excised for structural, biochemical and functional analyses.ResultsMyosin concentration in the diaphragm was decreased in MV versus CON, but not in MV + H versus CON. MV reduced diaphragm force by approximately 22% compared with CON. The force-generating capacity of diaphragm fibers from MV + H rats was approximately 14% lower compared with CON. Inflammatory cytokines were elevated in the diaphragm of MV rats, but not in the MV + H group. Diaphragm proteasome activity did not significantly differ between MV and CON. However, proteasome activity in the diaphragm of MV + H was significantly lower compared with CON. LC3B-II a marker of lysosomal autophagy was increased in both MV and MV + H. Incubation of MV + H diaphragm muscle fibers with the antioxidant dithiothreitol restored force generation of diaphragm fibers.ConclusionsHypercapnia partly protects the diaphragm against adverse effects of mechanical ventilation.
Highlights
Diaphragm weakness induced by prolonged mechanical ventilation may contribute to difficult weaning from the ventilator
For a more precise measurement of muscle atrophy, myosin heavy chain (MyHC) concentration was measured in diaphragm single fibers
Hypercapnia prevented the loss of myosin induced by mechanical ventilation; mean myosin concentration was higher in diaphragm fibers from the group of 18-hour mechanically ventilated rats (MV) + H group compared with the collection Immediately after anesthesia (CON) group (Figure 2b)
Summary
Diaphragm weakness induced by prolonged mechanical ventilation may contribute to difficult weaning from the ventilator. Hypercapnia is an accepted side effect of low tidal volume mechanical ventilation, but the effects of hypercapnia on respiratory muscle function are largely unknown. The present study investigated the effect of hypercapnia on ventilator-induced diaphragm inflammation, atrophy and function. It is well known that controlled mechanical ventilation adversely affects the respiratory muscles [1,2]. Levine and colleagues demonstrated that, in brain-dead patients, 18 to 69 hours of mechanical ventilation is associated with profound atrophy of the diaphragm [1]. Hypercapnia is a well-tolerated side effect of low tidal volume ventilation in patients with acute respiratory distress syndrome. Experimental studies indicate that hypercapnic acidosis may exert beneficial effects by reducing inflammation and lung injury during mechanical ventilation [5,6,7,8].
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