Mark A. Wineinger

Effect of voluntary wheel-running exercise on muscles of the mdx mouse

The purpose of this study is to determine whether dystrophin-deficient mdx mice are more susceptible to muscle injury and functional impairment than normal C57 mice when allowed to exercise voluntarily on mouse wheels. The mdx mice were significantly impaired when compared to controls as shown by functional, contractile and morphometric responses. The distance young mdx mice ran was 67-78% of young C57 mice, while adult mdx mice ran 31-48% of adult controls. After exercise the slow, oxidative soleus of young and adult mdx mice exhibited hypertrophy with no changes in strength or fatiguability, while the young C57 mice increased strength and the adults became less fatiguable. In the adult mdx mice the fast EDL, which is primarily glycolytic, exhibits slight hypertrophy with a loss of strength, while the young exhibit no changes. These results indicate that the mdx mouse adapts differently than the C57 mouse to even moderate exercise.

Effects of aging and voluntary exercise on the function of dystrophic muscle from mdx mice

To understand how exercise affects the contractile function of dystrophic muscle, we examined the effect of long-term voluntary exercise on mdx mice and related these effects to our findings in sedentary aging mice. Although the mdx mouse is the genetic homolog for Duchenne muscular dystrophy, it does not demonstrate the same progression in limb muscle dysfunction as Duchenne muscular dystrophy as it ages. We postulated that the sedentary lifestyle of this animal plays an important role in its minimal phenotypic expression. To examine the effect of exercise, eight C57BL/10 (C57) and eight mdx mice were allowed to run ad libitum for one year. Forty sedentary mdx mice and 40 sedentary C57 from one month to 18 months of age were used as controls. Contractile characteristics of the extensor digitorum longus and soleus muscles and morphometric characteristics of the mice were examined. The mdx mice ran approximately 45% fewer kilometers per day than C57 mice. Long-term voluntary running had beneficial training effects on both the old mdx mice and their C57 controls. The exercise ameliorated the age-associated loss in tension production that was observed in the soleus of sedentary mdx and sedentary C57 mice. There was a 9% reduction in the fatigability of the extensor digitorum longus muscle of the old mdx mice after the exercise. Despite these improvements, the old mdx mice exhibited significant functional deficits compared with their C57 controls. Our hypothesis, that long-term voluntary exercise would have a beneficial training effect on control mice and a deleterious effect on mdx mice as they aged, was not supported by this study. This study shows that dystrophin-less muscles from sedentary mice display significant signs of muscle damage, yet can respond beneficially to low-level voluntary running in a manner similar to that of the C57 control.

The effect of age and temperature on MDX muscle fatigue

We have studied the in vitro contractile and fatigue characteristics of extensor digitorum longus (EDL) muscles from 8‐ and 62‐week‐old dystrophin‐deficient (mdx) and control mice at 20°C and 35°C. There were no differences in fatigability at 20°C, but at 35°C the dystrophin‐deficient muscles demonstrated increased fatigability compared to controls, with the older mice exhibiting the greatest fatigue. These results suggest a temperature‐related mechanism of myofibrillar fatigue in dystrophin‐deficient EDL muscles.

Sensory axonopathy in mild to moderate peripheral arterial disease

The effect of mild to moderate arterial occlusive disease on peripheral nervous system conduction was prospectively investigated in 18 subjects and 18 control subjects, aged 40 to 85 years. Experimental and control subjects underwent a thorough history and physical followed by vascular and electrophysiologic studies. The primary outcome measure was the sensory nerve action potential. Although 33% of the subjects with peripheral arterial disease had experienced paresthesias, the clinical evaluation of sensation was relatively unaffected. Sensory conduction studies revealed 30% absent sural responses and 56% absent superficial peroneal nerve responses in subjects with peripheral arterial disease compared with 3 and 14% absent responses in control subjects, respectively (P = 0.044; 0.025). There were no differences in distal latency or sensory amplitude, although the superficial peroneal amplitude did approach significance (P = 0.06). No significant differences were found in motor distal latency, amplitude, or conduction velocity. Age, leg length, temperature, disease severity, presence of paresthesias, cholesterol levels, and past alcohol or tobacco ingestion did not account for the difference in sensory responses. These results support the presence of a mild sensory axonopathy in subjects with peripheral arterial disease. Electromyographers should be cognizant of absent distal responses from peripheral arterial disease so as not to ascribe the findings to an alternative pathology and should not attribute abnormal motor conduction results to the presence of this degree of peripheral arterial disease.

A reperfusion interval reduces the contractile deficit in skeletal muscle following tourniquet ischemia

Bloodless surgical procedures on the extremities are achieved by application of a pneumatic tourniquet. The ischemia produced has deleterious effects on nerve and muscle function. It has been suggested that temporary interruption of ischemia by a reperfusion interval can prevent muscle and nerve injury. We investigated the muscle and nerve response to 3 hours of tourniquet ischemia, with and without a reperfusion interval after the first 2 hours of application, in a rodent model. Morphometric, contractile, and histologic parameters were measured. Tourniquet ischemia, with and without a reperfusion interval, results in muscle injury and a transient depression of muscle function. Introduction of a reperfusion interval reduces the severity of injury and increases the early rate of recovery. However, the later stages of recovery appear to be unaffected by reperfusion.