Impact of prolonged mechanical ventilation on diaphragmatic protein synthesis

Abstract

Mechanical ventilation (MV) is a life‐saving intervention in patients suffering from respiratory failure. Unfortunately, prolonged MV promotes the rapid development of diaphragmatic atrophy due to increased proteolysis and decreased protein synthesis. These experiments investigated the influence of two different modes of MV on rat diaphragm protein synthesis. Specifically, we examined the mixed protein synthesis rate of diaphragm muscle proteins during controlled MV (CMV) which causes complete diaphragmatic inactivity and pressure support MV (PSV) which permits partial activity of the diaphragm. Our results reveal that compared to spontaneously breathing animals, diaphragm protein synthesis rates are not depressed during the first 6‐hours of PSV but are significantly decreased in animals exposed to CMV. However, the rates of diaphragm protein synthesis are depressed at similar levels in both CMV and PSV animals during 6–12 hours of MV. We conclude that while PSV can initially delay the MV‐induced decreases in diaphragm protein synthesis, this protective effect is rapidly lost after the first 6 hours of MV. NIH RO1 HL087839 (SKP)