In recent years, an increasing number of studies have demonstrated that a myopathy is present, contributes, and, to a certain extent, determines the pathogenesis of peripheral arterial occlusive disease (PAD). These works provide evidence that a state of repetitive cycles of exercise-induced ischemia followed by reperfusion at rest operates in PAD patients and mediates a large number of structural and metabolic changes in the muscle, resulting in reduced strength and function. The key players in this process appear to be defective mitochondria that, through multilevel failure in their roles as energy, oxygen radical species, and apoptosis regulators, produce and sustain a progressive decline in muscle performance. In this 2-part review, we highlight the currently available evidence that characterizes the nature and mechanisms responsible for this myopathy. In part 1, the authors review the functional and histomorphological characteristics of the myopathy and focus on the biochemistry and bioenergetics of its mitochondriopathy. In part 2, they then review accumulating evidence that oxidative stress related to ischemia reperfusion is probably the major operating mechanism of PAD myopathy. Important new findings of a possible neuropathy and a shift in muscle fiber type are also reviewed. Learning more about these mechanisms will enhance our understanding of the degree to which they are preventable and treatable.

In recent years, an increasing number of studies have demonstrated that a myopathy is present, contributes, and, to a certain extent, determines the pathogenesis of peripheral arterial occlusive disease. These works provide evidence that a state of repetitive cycles of exercise-induced ischemia followed by reperfusion at rest operates in patients with peripheral arterial occlusive disease and mediates a large number of structural and metabolic changes in the muscle, resulting in reduced strength and function. The key players in this process appear to be defective mitochondria that, through multilevel failure in their roles as energy, oxygen radical species, and apoptosis regulators, produce and sustain a progressive decline in muscle performance. In this 2-part review, the currently available evidence that characterizes the nature and mechanisms responsible for this myopathy is highlighted. In part 1, the functional and histomorphological characteristics of the myopathy were reviewed, and the main focus was on the biochemistry and bioenergetics of its mitochondriopathy. In part 2, accumulating evidence that oxidative stress related to ischemia reperfusion is probably the major operating mechanism of peripheral arterial occlusive disease myopathy is reviewed. Important new findings of a possible neuropathy and a shift in muscle fiber type are also reviewed. Learning more about these mechanisms will enhance our understanding of the degree to which they are preventable and treatable.

This study examined the role of heating on oxidative stress and muscle mass in immobilized limbs. Rats were divided into three groups ( n = 9/group): a control group (Con), an immobilized group (Im), and an immobilized and heated group (ImH). Rats were immobilized in the plantarflexed position for 8 days. The core temperature of the ImH group was elevated to 41–41.5°C on alternating days and maintained for 30 min before cooling. On day 8, both heat shock protein 25 (HSP25) and HSP72 were markedly elevated in the ImH compared with the Im group, whereas results in the Im group were not different from Con. Most notably, the ImH group had significantly larger solei compared with the Im group, which were less than those shown in the Con group. Furthermore, immobilization alone caused a significant increase in oxidative damage, and the addition of heating to immobilization significantly reduced oxidative damage. In an effort to further identify the cause of this protective effect, antioxidant enzyme activities were assessed. CuZnSOD was sharply elevated in Im compared ( P < 0.025) with that in the Con and reduced in the ImH group compared with that in the Im group ( P < 0.025). Catalase was elevated 8% ( P < 0.025) in the Im group compared with the Con group and was similar to the ImH group. Glutathione peroxidase, glutathione reductase, and MnSOD did not differ between groups. These data indicate that heating provides protection against oxidative stress and preserves muscle mass during disuse atrophy. These data also suggest that antioxidant protection is not conferred via antioxidant enzymes, and HSPs may play an important role.

Heat stress is associated with death and other maladaptions including muscle dysfunction and impaired growth across species. Despite this common observation, the molecular effects leading to these pathologic changes remain unclear. The purpose of this study was to determine the extent to which heat stress disrupted redox balance and initiated an inflammatory response in oxidative and glycolytic skeletal muscle. Female pigs (5–6/group) were subjected to thermoneutral (20 °C) or heat stress (35 °C) conditions for 1 or 3 days and the semitendinosus removed and dissected into red (STR) and white (STW) portions. After 1 day of heat stress, relative abundance of proteins modified by malondialdehyde, a measure of oxidative damage, was increased 2.5-fold (P < 0.05) compared with thermoneutral in the STR but not the STW, before returning to thermoneutral conditions following 3 days of heat stress. This corresponded with increased catalase and superoxide dismutase-1 gene expression (P < 0.05) and superoxide dismuta...