Abstract
Duchenne muscular dystrophy (DMD) is a uniformly fatal condition of striated muscle wasting resulting in premature death from respiratory and/or cardiac failure. Symptomatic therapy has prolonged survival by limiting deaths resulting from respiratory insufficiency, but there is currently no effective therapy for most patients with DMD. This grim prognosis has led patients and their families to seek unproven therapeutic approaches. One such approach is the use of hyperbaric therapies, which 14% of DMD patients self-report using. The primary goal of this study was to determine if intermittent hyperbaric exposure altered the muscle function of the mdx mouse, a genetic model of DMD. To do this, mdx mice were exposed to three daily 90-minute 1.3 atmosphere hyperbaric exposures for 4 weeks. Skeletal muscle, respiratory, and cardiac function were assessed in treated and untreated wild type and dystrophic mice. The results of these studies find that hyperbaric and hyperoxic approaches resulted in increased cardiac fibrosis in dystrophic mice and no beneficial effects on the functional parameters measured. These data suggest that these oxygen-based therapies are unlikely to provide therapeutic benefit to DMD patients.
Highlights
Duchenne muscular dystrophy (DMD) is a devastating disease characterized by muscle wasting, respiratory insufficiency, and cardiomyopathy[1,2,3]
Mice were subjected to three 90-minute periods of hyperoxia/hyperbaric conditions each day (Fig. 1). These periods occurred at set times during the day throughout the protocol. This protocol represents a high degree of hyperbaric exposure and is similar to protocols recommended to DMD patients
The primary motivating factor for these studies was to determine if hyperbaric therapy would have an effect on the pathophysiology of Duchenne muscular dystrophy (DMD) as manifested in the mdx mouse
Summary
Duchenne muscular dystrophy (DMD) is a devastating disease characterized by muscle wasting, respiratory insufficiency, and cardiomyopathy[1,2,3] This disease is uniformly fatal and there are currently no therapies that are effective for all DMD patients. Hyperbaric oxygen therapy consists of placing patients into environments with elevations in barometric pressure, sometimes with additional supplemental oxygen. This increases the concentrations of oxygen available to the body. It is hypothesized that any beneficial effects of hyperbaric exposure will be the result of increased oxygen delivery To control for this possibility, we have included an experimental group in which only the levels of ambient oxygen are changed. The study reported here assessed the effect of 4 weeks of hyperbaric or hyperoxic therapy on the skeletal muscle, respiratory muscle, and cardiac function in the mdx mouse
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