THE CUMULATIVE EFFECTS OF AGING AND DIAPHRAGM UNLOADING ON IN VITRO DIAPHRAGMATIC FUNCTION

Evidence indicates that aged locomotor muscle suffers exaggerated atrophy during periods of unloading. It is also established that aging is associated with a reduction in maximal specific tension (Po) in both locomotor muscles and the diaphragm. Further, we have demonstrated that unloading the diaphragm, via mechanical ventilation (MV), results in significant diaphragmatic atrophy and contractile dysfunction in young adult animals. It is currently unkown if unlloading the diaphragm results in greater contractile dysfunction in old animals compared to young adults. PURPOSE: We tested the hypothesis that compared to young adult animals, aging would exacerbate MV-induced diaphragmatic contractile dysfunction. METHODS: Fisher Brown Norway Cross rats (4 mo. (young) and 30 mo. (old)) were assigned to either the control group (CON) or the mechanical ventilation group (MV). MV rats were anesthetized, tracheostomized, and ventilated with 21% O2 for 12 hours. MV animals were fed enterally with a gastric catheter and arterial blood pressure, pH, and blood gas homeostasis were maintained throughout the experimental period. Animals in the CON group were acutely anesthetized but were not exposed to MV. Muscle strips from the mid-costal diaphragm were removed from each experimental animal and contractile properties were studied in vitro to determine the effects of MV on diaphragmatic Po. RESULTS: Compared to young CON, aging (old CON) was associated with a 20% decrease in Po (26.4 N/cm2 vs. 20.7 N/cm2). MV induced similar relative losses (−25%) in diaphragmatic Po in both young and old MV animals (19.7 N/cm2 vs. 15.5 N/cm2). Further, compared to young CON, the combined effects of aging and MV resulted in a 40% decrement in diaphragmatic Po. CONCLUSIONS: Unloading the diaphragm by MV results in a significant decrease in diaphragmatic Po in both young and old animals. However, these data do not support the hypothesis that aging exacerbates the relative MV-induced impairment in diaphragmatic Po. Nonetheless, the additive effects of aging and MV may place constraints on the diaphragmatic force reserve during periods of increased loads and could lead to respiratory failure. National Institutes of Health (R01 HL62361) awarded to S.K. Powers