Increased levels of apoptosis in gastrocnemius skeletal muscle in patients with peripheral arterial disease

Mitchell, Ryan M.; Duscha, Brian D.; Robbins, Jennifer L.; Redfern, Shelley I.; Chung, Jayer; Bensimhon, Daniel; Kraus, William E.; Hiatt, William R.; Regensteiner, Judith G.; Annex, Brian H.

doi:10.1177/1358863x07084858

Cited by 61 publications

(51 citation statements)

References 19 publications

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“…[122][123][124][125] These structural changes may be mediated, in part, by higher levels of inflammatory mediators in PAD. 126 On the basis of biopsy specimens from the gastrocnemius muscles of patients with PAD, ≈4% of gastrocnemius cells are apoptotic, and caspase-3 levels are twice as high as in patients without PAD.…”

Section: Skeletal Muscle Structural Abnormalitiesmentioning

confidence: 99%

“…126 On the basis of biopsy specimens from the gastrocnemius muscles of patients with PAD, ≈4% of gastrocnemius cells are apoptotic, and caspase-3 levels are twice as high as in patients without PAD. 125 Selective fiber type switching from type I (aerobic) to type II (glycolytic) fibers may impair skeletal muscle performance and has been associated with decreased exercise tolerance. 123 Decreased expression of myosin heavy-chain isoform II in patients with PAD may also result in altered muscle contraction kinetics and decreased cellular efficiency.…”

Section: Skeletal Muscle Structural Abnormalitiesmentioning

confidence: 99%

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Pathogenesis of the Limb Manifestations and Exercise Limitations in Peripheral Artery Disease

Hiatt¹,

Armstrong²,

Larson³

et al. 2015

Circulation Research

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133

118

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P eripheral artery disease (PAD) is initiated by atherogenic mechanisms common to all major vascular territories but encompasses several distinctly important clinical sequelae.1 The global burden of PAD is large and rising, with substantial morbidity and mortality found in high-, middle-, and low-income countries. 2 The atherosclerotic occlusive disease underlying PAD is associated with an exercise limitation in the majority of patients, whereas the classic symptoms of intermittent claudication, ischemic rest pain, and ischemic ulceration are less common manifestations. 3 Patients with PAD are also at increased risk of myocardial infarction, ischemic stroke, heart failure, renovascular hypertension, and vascular death reflecting the systemic atherosclerotic burden. [4][5][6] The epidemiology of Peripheral Artery Disease Compendium© 2015 American Heart Association, Inc. The diagnosis of PAD can be ascertained by simple hemodynamic measurements, in particular, the ankle-brachial index (ABI), a test performed by measuring the systolic blood pressure in each arm and the dorsalis pedis and posterior tibial arteries of each ankle. The highest of the dorsalis pedis or posterior tibial artery pressures is the numerator of the ABI specific to each leg, whereas the highest arm pressure on either side is the denominator. A ratio of <0.90 in either leg is considered hemodynamic evidence of PAD. 16 When imaged, PAD can be characterized as one or more arterial stenoses or occlusions involving the distal aorta, iliac, femoral, popliteal, or tibial arteries. 17The underlying mechanisms responsible for the functional limitations in PAD are hemodynamic in origin, which affects the supply of oxygen and substrates to metabolically active tissue: skeletal muscle in the case of intermittent claudication and skin and subcutaneous tissues in the case of critical leg ischemia. However, additional pathophysiologic mechanisms contribute to the limb manifestations, where a reduction in blood flow alone does not fully account for the exercise limitation. Recent research into the pathophysiology of this exercise limitation has identified several important sequelae resultant from the chronic hemodynamic deficit. These changes affecting the vasculature and skeletal muscle distal to the primary hemodynamic lesions likely contribute to the mechanisms of exercise limitation in PAD. These advances are reviewed here with an additional focus on identifying possible future therapeutic strategies. Symptomatic Manifestations and Exercise Limitations in PADIn the coronary circulation, plaque rupture leading to acute ischemic events is a common clinical presentation; in PAD, progressive atherosclerosis leading to chronic stenosis and occlusion, often in series, in the arteries supplying the lower extremities dominates the symptomatic manifestations.6 Limb SymptomsPatients with PAD may present with a range of limb symptoms. Most patients are either asymptomatic or have atypical limb symptoms during exercise, whereas only a third have typical symptoms of c...

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Section: Skeletal Muscle Structural Abnormalitiesmentioning

confidence: 99%

Section: Skeletal Muscle Structural Abnormalitiesmentioning

confidence: 99%

Pathogenesis of the Limb Manifestations and Exercise Limitations in Peripheral Artery Disease

Hiatt¹,

Armstrong²,

Larson³

et al. 2015

Circulation Research

Self Cite

133

118

View full text Add to dashboard Cite

show abstract

“…12,17,18 Another important factor in patients with PVI is the presence of pain in areas distal to damage caused by ischemia provoked by the pathology itself 19 and, as a result, these patients tend to have lower physical activity levels and impaired walking capacity, all of which results in a general process of loss of fitness, inactivity and worsened quality-of-life. 20 Arterial damage may be exacerbated by the abnormal hemodynamic response, chronic venous insufficiency or heart failure; it was notable that patients with PVI achieved shorter distances in the 6MWT than patients with HF alone.…”

Section: Discussionmentioning

confidence: 99%

Peripheral vascular insufficiency impairs functional capacity in patients with heart failure

et al. 2014

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INTRODUCTION: Heart failure (HF) is a complex syndrome in which effort limitation is associated with deterioration of peripheral musculature. Improving survival rates among these patients have led to the appearance of cases in which other pathologies are associated with HF, such as peripheral vascular insufficiency (PVI). The combination of these two pathologies is common, with significant repercussions for affected patients. OBJECTIVE: To compare functional limitations and quality of life between patients with HF in isolation or HF + PVI. METHOD: Twelve patients with HF+PVI were paired to 12 patients with HF in isolation. All had ejection fraction <40%. The following were conducted: 6 minute walk test (6MWT), chair test (CT), step test (ST), one repetition maximum test (1RM) and quality of life questionnaire. RESULTS: The results for the 6MWT (311±27 vs. 447±29), ST (49±3 vs. 81±10) and CT (17±1 vs. 21±1) were lower in the HF+PVI group than in the HF group (p<0.05). The HF+PVI group exhibited a reduction in the number of steps taken from the first to the second minute of the ST, in relation to the HF group. The HF group exhibited better HR recovery than the HF+PVI group (50±4 vs. 26±3; p<0.05). No differences were found in results for the Borg scale, the peripheral muscle strength test (1RM) or the questionnaires (p>0.05). CONCLUSIONS: The study participants who had mixed disease exhibited a greater degree of functional impairment than the group with HF, without reporting worsened quality of life.

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“…23 In PAD patients' calf muscles, increased muscle cell apoptosis and decreased capillary density are noted at the cellular and tissue levels, and muscle energetics are associated with mitochondrial dysfunction. 34, 35 Bauer et al reported that mitochondrial dysfunction may affect the muscle oxygen utilization rate and accelerate endothelial cell damage. 36, 37 We consider that our SW therapy may contribute, at least in part, to an improvement in mitochondrial dysfunction and muscle oxygen utilization.…”

Section: Study Limitationsmentioning

confidence: 99%

Extracorporeal Shock Wave Therapy Improves the Walking Ability of Patients With Peripheral Artery Disease and Intermittent Claudication

Serizawa

Ito

Kawamura

et al. 2012

Circ J

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Increased levels of apoptosis in gastrocnemius skeletal muscle in patients with peripheral arterial disease

Cited by 61 publications

References 19 publications

Pathogenesis of the Limb Manifestations and Exercise Limitations in Peripheral Artery Disease

Pathogenesis of the Limb Manifestations and Exercise Limitations in Peripheral Artery Disease

Peripheral vascular insufficiency impairs functional capacity in patients with heart failure

Extracorporeal Shock Wave Therapy Improves the Walking Ability of Patients With Peripheral Artery Disease and Intermittent Claudication

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