Hypercapnia attenuates ventilator-induced diaphragm atrophy and modulates dysfunction

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.

Effects of Lower Tidal Volume on Ventilator-Induced Diaphragmatic Dysfunction

“…Sasson et al [24] also reported that positive end-expiratory airway pressure does not aggravate VIDD in rabbits [24]. Schellekens et al [25] reported that hypercapnea partly protects the diaphragm against the adverse effects of MV in a rat VIDD model. This study had the limitation that although mice ventilated at higher tidal volume had greater diaphragm weakness than those ventilated at lower tidal volume or controls, there were no other differences in the results of pulmonary function test, histological evaluation, or biochemical evaluation between groups.…”

Hypercapnia

“…An experimental study in rats suggests that hypercapnia may protect against this problem [26]. Here, diaphragm myofiber myosin concentration was significantly increased compared with controls; in addition, tumor necrosis factor-a, interleukin-1b, and keratinocyte-derived chemokines were all significantly decreased in diaphragm homogenates of hypercapnia animals.…”

Ventilator-induced diaphragmatic dysfunction

“…In this regard, piglets ventilated with increased dead space to achieve moderate hypercapnic acidosis (pCO 2 55-70 mmHg) showed preserved diaphragmatic force production after 72 h of mechanical ventilation [49]. A similar level of hypercapnia induced by adding inspired CO 2 also attenuated several aspects of VIDD in rats [50]. The cellular mechanisms underlying the improvements associated with hypercapnia are yet to be elucidated but likely involve anti-inflammatory and/or antioxidant effects.…”