Positive end-expiratory airway pressure does not aggravate ventilator-induced diaphragmatic dysfunction in rabbits

Catherine SH Sassoon, Ercheng Zhu, Liwei Fang, Gary C Sieck, Scott K Powers

IntroductionImmobilization of hindlimb muscles in a shortened position results in an accelerated rate of inactivity-induced muscle atrophy and contractile dysfunction. Similarly, prolonged controlled mechanical ventilation (CMV) results in diaphragm inactivity and induces diaphragm muscle atrophy and contractile dysfunction. Further, the application of positive end-expiratory airway pressure (PEEP) during mechanical ventilation would result in shortened diaphragm muscle fibers throughout the respiratory cycle. Therefore, we tested the hypothesis that compared to CMV without PEEP; the combination of PEEP and CMV would accelerate CMV-induced diaphragm muscle atrophy and contractile dysfunction. To test this hypothesis, we combined PEEP with CMV or with assist-control mechanical ventilation (AMV) and determined the effects on diaphragm muscle atrophy and contractile properties.MethodsThe PEEP level (8 cm H2O) that did not induce lung over-distension or compromise circulation was determined. In vivo segmental length changes of diaphragm muscle fiber were then measured using sonomicrometry. Sedated rabbits were randomized into groups: surgical control, and those receiving CMV, AMV, continuous positive airway pressure (CPAP) with, or without PEEP for 2 days. In vitro diaphragmatic force, diaphragm muscle morphometry, myosin heavy-chain (MyHC) protein isoforms, caspase-3, insulin-like growth factor-1 (IGF-1), muscle atrophy F-box (MAFbx) and muscle ring finger-1 (MuRF1) mRNA were measured.ResultsPEEP shortened end-expiratory diaphragm muscle length by 15%, 14% and 12% with CMV, AMV and CPAP, respectively. Combined PEEP and CMV reduced tidal excursion of segmental diaphragm muscle length, consequently tidal volume (VT) decreased. VT was maintained with combined PEEP and AMV. CMV alone decreased maximal tetanic force (Po) production by 35% versus control (P <0.01). Combined PEEP and CMV did not decrease Po further. Po was preserved with AMV with or without PEEP. Diaphragm muscle atrophy did not occur in any fiber types. Diaphragm MyHC shifted to fast isoform in the combined PEEP and CMV group. In both CMV, and combined PEEP and CMV, IGF-1 mRNAs were suppressed, while Caspase-3, MAFbx and MuRF1 mRNA expression was elevated compared to control.ConclusionsTwo days of diaphragm muscle fiber shortening with PEEP did not exacerbate CMV-induced diaphragm muscle dysfunction.