Short-Duration Mechanical Ventilation Enhances Diaphragmatic Fatigue Resistance but Impairs Force Production

Abstract

s: Mechanical ventilation (MV) is a life-support measure for patients who cannot maintain adequate alveolar ventilation. Following prolonged MV, difficulty in weaning patients from the ventilator can occur, and it has been postulated that difficult weaning is linked to respiratory muscle dysfunction. We tested the hypothesis that 18 h of controlled MV will diminish diaphragmatic maximal tetanic specific tension (force per cross-sectional area of muscle) without impairing diaphragmatic fatigue resistance. To test this postulate, adult Sprague-Dawley rats were randomly classified into one of two experimental groups: (1) control group (n = 8), and (2) 18-h MV group (n = 6). MV-treated animals were anesthetized, tracheostomized, and received room air ventilation. Animals in the control group were acutely anesthetized but did not receive MV. Muscle strips from the mid-costal diaphragm were removed from both experimental groups, and contractile properties were studied in vitro to determine the effects of MV on diaphragmatic endurance and maximal force production. Diaphragmatic endurance was investigated by measuring tension development during repeated contractions throughout a 30-min fatigue protocol. MV resulted in a reduction (p < 0.05) in diaphragmatic maximal specific tension (control group, 26.8 +/- 0.2 Newtons/cm(2) vs MV group, 21.3 +/- 0.6 Newtons/cm(2)). Compared to the control group, diaphragms from MV-treated animals maintained higher (p < 0.05) percentages of the initial force production throughout the fatigue protocol. The observed improvement in fatigue resistance was associated with an increase in diaphragmatic oxidative and antioxidant capacity as evidenced by increases (p < 0.05) in both citrate synthase and superoxide dismutase activities. However, by comparison to the control group, diaphragms from MV-treated animals generated less (p < 0.05) absolute specific force throughout the fatigue protocol. These data indicate that 18 h of MV enhances diaphragmatic fatigue resistance but impairs diaphragmatic specific tension.