Limb Stress-Rest Perfusion Imaging With Contrast Ultrasound for the Assessment of Peripheral Arterial Disease Severity

Lindner, Jonathan R.; Womack, Lisa; Barrett, Eugene J.; Weltman, Judy Y.; Price, W. Islwyn; Harthun, Nancy L.; Kaul, Sanjiv; Patrie, James T.

doi:10.1016/j.jcmg.2008.04.001

Cited by 103 publications

(111 citation statements)

References 28 publications

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“…We hypothesize that the changes in capillary structure (BM thickening, collapsed lumen, swollen EC) contribute to impaired microvascular muscle perfusion in PAD (33). This is likely to impede the diffusion of oxygen and nutrients into skeletal muscle fibers of the IC patients, thereby compromising their energy supply and contractile capacity.…”

Section: Discussionmentioning

confidence: 99%

Capillary ultrastructure and mitochondrial volume density in skeletal muscle in relation to reduced exercise capacity of patients with intermittent claudication

Baum

Torchetti

Malik

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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(PAD). Impaired limb blood flow is a major casual factor of lower exercise tolerance in PAD but cannot entirely explain it. We hypothesized that IC is associated with structural changes of the capillary-mitochondria interface that could contribute to the reduction of exercise tolerance in IC patients. Capillary and mitochondrial morphometry were performed after light and transmission electron microscopy using vastus lateralis muscle biopsies of 14 IC patients and 10 age-matched controls, and peak power output (PPO) was determined for all participants using an incremental single-leg kneeextension protocol. Capillary density was lower (411 Ϯ 90 mm Ϫ2 vs. 506 Ϯ 95 mm Ϫ2 ; P Յ 0.05) in the biopsies of the IC patients than in those of the controls. The basement membrane (BM) around capillaries was thicker (543 Ϯ 82 nm vs. 423 Ϯ 97 nm; P Յ 0.01) and the volume density of mitochondria was lower (3.51 Ϯ 0.56% vs. 4.60 Ϯ 0.74%; P Յ 0.01) in the IC patients than the controls. In the IC patients, a higher proportion of capillaries appeared with collapsed slit-like lumen and/or swollen endothelium. PPO was lower (18.5 Ϯ 9.9 W vs. 33.5 Ϯ 9.4 W; P Յ 0.01) in the IC patients than the controls. We suggest that several structural alterations in skeletal muscle, either collectively or separately, contribute to the reduction of exercise tolerance in IC patients. capillary; morphometry; peripheral arterial disease; skeletal muscle; transmission electron microscopy PERIPHERAL ARTERIAL DISEASE (PAD) is an atherosclerotic disease characterized by stenosis or occlusion of the conduit arteries of the lower limbs (20,36). Risk factors associated with PAD include advancing age, cigarette smoking, diabetes mellitus, arterial hypertension, and disturbances in lipid metabolism (12). While many PAD patients are asymptomatic, the arterial narrowing leads to ischemia and hypoxia of the supplied tissues and in severe cases, this manifests as critical limb ischemia (CLI), usually requiring surgical interventions. Intermittent claudication (IC), which is typically described as a cramp-like muscle pain during exercise, is the most commonly reported symptom of PAD and is usually the first noted symptom of the disease.Patients with IC have limited muscular strength and endurance capacities (35), reduced cardiorespiratory fitness (V O 2 peak ), and demonstrate reduced oxygen uptake kinetics at the onset of exercise (6). They also exhibit a significantly reduced tolerance for physical activities such as walking and cycling (2, 13). This reduction in exercise tolerance leads to functional impairments that are similar to those observed in patients with heart failure (31) and contributes to their impaired mobility, reduced quality of life, and elevated risk for the development of cardiovascular complications (17).Impaired limb blood flow is commonly assumed to be the main casual factor of the reduction in exercise tolerance in PAD but cannot entirely explain it. For example, restoration of blood flow capacity with percutaneous endovascular revascularizat...

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Section: Discussionmentioning

confidence: 99%

Capillary ultrastructure and mitochondrial volume density in skeletal muscle in relation to reduced exercise capacity of patients with intermittent claudication

Baum

Torchetti

Malik

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In this context, laser Doppler flowmetry can be used to assess the local microcirculation, 8 and contrast-enhanced ultrasound has been introduced recently for the determination of tissue perfusion in patients with PAD. 23,24 Moreover, functional assessment with magnetic resonance imaging has been described in single individuals but not yet evaluated in a clinical trial. 8,25 Apart from the invasive measurement of antegrade flow velocity in a single patient in the early days of angiogenesis research (certainly without balloon occlusion), 26 no attempts have been made to directly quantify the collateral circulation of the lower limb.…”

Section: Discussionmentioning

confidence: 99%

Direct Quantitative Assessment of the Peripheral Artery Collateral Circulation in Patients Undergoing Angiography

et al. 2013

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Background-Despite the fact that numerous studies have pursued the strategy of improving collateral function in patients with peripheral artery disease, there is currently no method available to quantify collateral arterial function of the lower limb. Methods and Results-Pressure-derived collateral flow index (CFIp, calculated as (occlusive pressure−central venous pressure)/(aortic pressure−central venous pressure); pressure values in mm Hg) of the left superficial femoral artery was obtained in patients undergoing elective coronary angiography using a combined pressure/Doppler wire (n=30). Distal occlusive pressure and toe oxygen saturation (Sao 2 ) were measured for 5 minutes under resting conditions, followed by an exercise protocol (repetitive plantar-flexion movements in supine position; n=28). In all patients, balloon occlusion of the superficial femoral artery over 5 minutes was painless under resting conditions. CFIp increased during the first 3 minutes from 0.451±0.168 to 0.551±0.172 (P=0.0003), whereas Sao 2 decreased from 98±2% to 93±7% (P=0.004). Maximal changes of Sao 2 were inversely related to maximal CFIp (r 2 =0.33, P=0.003). During exercise, CFIp declined within 1 minute from 0.560±0.178 to 0.393±0.168 (P<0.0001) and reached its minimum after 2 minutes of exercise (0.347±0.176), whereas Sao 2 declined to a minimum of 86±6% (P=0.002). Twenty-five patients (89%) experienced pain or cramps/tired muscles, whereas 3 (11%) remained symptom-free for an occlusion time of 10 minutes. CFIp values were positively related to the pain-free time span (r 2 =0.50, P=0.002). Conclusions-Quantitatively assessed collateral arterial function at rest determined in the nonstenotic superficial femoral artery is sufficient to prevent ischemic symptoms during a total occlusion of 5 minutes. During exercise, there is a decline in CFIp that indicates a supply-demand mismatch via collaterals or, alternatively, a steal phenomenon. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01742455.(Circulation. 2013;128:737-744.)

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“…72 Similarly, imaging studies using MRI or contrast-enhanced ultrasound have demonstrated lower microvascular flow in the calf musculature in PAD patients. 73, 74 Exercise blood flow measured by contrast ultrasound was related to claudication time in a treadmill test. 74 Also, reduced skeletal muscle blood flow as measured by MR during exercise was associated with impaired 6-minute walking time.…”

Section: Systemic and Local Inflammationmentioning

confidence: 99%

“…73, 74 Exercise blood flow measured by contrast ultrasound was related to claudication time in a treadmill test. 74 Also, reduced skeletal muscle blood flow as measured by MR during exercise was associated with impaired 6-minute walking time. 43 Taken together, evidence from clinical investigations supports the concept that microcirculatory dysfunction affects limb function in patients with PAD, and that enhanced calf blood flow may be a therapeutic avenue.…”

Section: Systemic and Local Inflammationmentioning

confidence: 99%

Pathophysiology of Intermittent Claudication in Peripheral Artery Disease

Hamburg

Creager

2017

Circ J

157

124

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estimates a more than 30% increase in deaths and disability attributable to PAD between 2005 and 2015, which is largely determined by population aging. 3,12 PAD prevalence escalates with advancing age, affecting 1 in 10 adults older than 70 years. In addition to age, smoking and diabetes are the strongest risk factors for PAD across the world. A comprehensive global evaluation of PAD found that its prevalence and risk factors are similar in high-income countries to low-and middle-income countries. 2,13 Lower socioeconomic status is a newly recognized risk factor for PAD. 14 Importantly, there has been a greater increase in PAD prevalence in low-and middle-income countries, rising by 28.7% from 2000 to 2010 as compared with 13.1% in high-income countries. 2, 15 The changing burden of PAD is also greater in women as compared with men.The health implications of PAD derive from both its limb and cardiovascular manifestations. Consistent with the systemic nature of atherosclerosis, polyvascular disease is common in patients with PAD. 16 In the REACH registry, 61% of PAD patients had concomitant coronary artery disease (CAD) and/or cerebrovascular disease. 16 Thus, the presence of PAD portends a high risk for subsequent cardiovascular events. A meta-analysis of over 48,000 participants in population-based cohort studies demonstrated that a low ankle-brachial index (ABI) predicted a 2-fold risk of death, cardiovascular death, and major coronary events at all ranges of the Framingham Risk Score. 4 Further, the elevated risk of cardiovascular events is present in both symptomatic and asymptomatic patients. 17 Patients with atherosclerotic disease in more than 1 vascular territory have particularly poor outcomes. 6 In the over 5,000 Japanese T here is growing recognition of the effect of peripheral artery disease (PAD) on cardiovascular health. 1 Recent studies indicate that, globally, over 200 million adults have PAD, 2,3 which is an expression of systemic atherosclerosis and well-established as heightening the risk for cardiovascular events. 4-6 The limb manifestations of PAD induce considerable suffering. Patients with PAD experience intermittent claudication, characterized as exertional leg pain that limits walking ability, and often times, disability. 7-9 Current medical therapies to reduce the burden of lower extremity symptoms in patients with PAD are limited. Revascularization by endovascular intervention or surgical reconstruction is used to treat lifestyle-limiting claudication if patients do not respond adequately to medical therapy including exercise training. Indeed, lower extremity revascularization with endovascular approaches has undergone a dramatic increase in use. 10 Though endovascular therapy improves blood flow and function, there are significant associated risks, and durability may be limited, especially in infrainguinal disease. Abundant evidence demonstrates the benefits of exercise therapy in claudication, yet the mechanisms underlying the beneficial effects remain incompletely defined. 11 Thus, ...

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Limb Stress-Rest Perfusion Imaging With Contrast Ultrasound for the Assessment of Peripheral Arterial Disease Severity

Cited by 103 publications

References 28 publications

Capillary ultrastructure and mitochondrial volume density in skeletal muscle in relation to reduced exercise capacity of patients with intermittent claudication

Capillary ultrastructure and mitochondrial volume density in skeletal muscle in relation to reduced exercise capacity of patients with intermittent claudication

Direct Quantitative Assessment of the Peripheral Artery Collateral Circulation in Patients Undergoing Angiography

Pathophysiology of Intermittent Claudication in Peripheral Artery Disease

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