Chest
Volume 123, Issue 1, January 2003, Pages 195-201
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Laboratory and Animal Investigations
Short-Duration Mechanical Ventilation Enhances Diaphragmatic Fatigue Resistance but Impairs Force Production

https://doi.org/10.1378/chest.123.1.195Get rights and content

Study objectives

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.

Design

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.

Results

MV resulted in a reduction (p < 0.05) in diaphragmatic maximal specific tension (control group, 26.8 ± 0.2 Newtons/cm2 vs MV group, 21.3 ± 0.6 Newtons/cm2). 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.

Conclusions

These data indicate that 18 h of MV enhances diaphragmatic fatigue resistance but impairs diaphragmatic specific tension.

Section snippets

Experimental Animals and Research Design

These experiments were approved by the University of Florida animal use committee, and followed the guidelines for animal experiments established by the National Institutes of Health. Healthy, female, young adult (4-month-old) Sprague-Dawley rats were individually housed, fed rat chow and water ad libitum, and were maintained on a 12-h light/dark cycle for 3 weeks prior to initiation of these experiments. Animals were randomly assigned to one of two experimental groups: control animals (n = 8)

Systemic and Biological Response to MV

No animals were eliminated due to infection. However, one animal from the MV group was eliminated from our analysis because the postmortem examination revealed evidence of lung barotrauma. Of the animals included in our analysis, initial and final body weights did not differ (p > 0.05) between control animals and MV-treated animals. Importantly, 18 h of MV did not result in a significant change (p > 0.05) in animal body weight (data not shown). These results indicate that our schedule of

Overview of Principle Findings

Although previous experiments have reported that relatively short-duration MV results in diaphragmatic force deficits, the present experiments provide important new information regarding the influence of controlled MV on diaphragmatic endurance. Our results support the hypothesis that 18 h of MV results in a significant reduction (approximately 20%) in diaphragmatic specific Po. Furthermore, these data support the notion that 18 h of MV does not accelerate the rate of diaphragmatic fatigue

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    This work was supported by grants from the American Lung Association-Florida and the National Institutes of Health (R01 HL62361) awarded to Dr. Powers.

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