Limb Perfusion During Exercise Assessed by Contrast Ultrasound Varies According to Symptom Severity in Patients with Peripheral Artery Disease

Davidson, Brian P.; Hodovan, James; Mason, O’Neil; Moccetti, Federico; Gupta, Avi; Muller, Matthew; Belcik, J. Todd; Annex, Brian H.; Lindner, Jonathan R.

doi:10.1016/j.echo.2019.05.001

Cited by 10 publications

(5 citation statements)

References 32 publications

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“…Similar observations have been reported in patients with PAD. For example, basal/resting microvascular blood volume and flow, measured in the gastrocnemius muscle using contrast-enhance ultrasound, were not different between control subjects without PAD and patients with mild-to-moderate PAD, however differences between these groups were revealed by treadmill or calf muscle exercise (109)(110)(111). Similar observations have been reported using magnetic resonance imaging to assess calf muscle perfusion at rest and in response to exercise (112,113).…”

Section: Exercise Training Interventions Including Home-based Exercisesupporting

confidence: 55%

A 6-minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models

Palzkill,

Tan,

Tice

et al. 2024

Preprint

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Objective: The translation of promising therapies from pre-clinical models of hindlimb ischemia (HLI) to patients with peripheral artery disease (PAD) has been inadequate. While this failure is multifactorial, primary outcome measures in preclinical HLI models and clinical trials involving patients with PAD are not aligned well. For example, laser Doppler perfusion recovery measured under resting conditions is the most used outcome in HLI studies, whereas clinical trials involving patients with PAD primarily assess walking performance. Here, we develop a 6-min limb function test for preclinical models that assesses muscular performance and hemodynamics congruently. Approach and Results: We developed an in situ 6-min limb function test that involves repeated isotonic (shortening) contractions performed against a submaximal load. Continuous measurement of muscle blood flow was performed using laser Doppler flowmetry. Quantification of muscle power, work, and perfusion are obtained across the test. We performed HLI on several mouse strains: C57BL6J, BALBc/J, and MCK-PGC1a (muscle-specific overexpression of PGC1a). Additional experiments were performed using an exercise intervention (voluntary wheel running) following HLI. The 6-min limb function test was successful at detecting differences in limb function of C57BL6/J and BALBc/J mice subjected to HLI with effect sizes superior to laser Doppler. C57BL6/J mice randomized to exercise therapy following HLI had smaller decline in muscle power, greater hyperemia, and performed more work compared to non-exercise controls with HLI. Mice with muscle-specific overexpression of PGC1a had no differences in perfusion recovery in resting conditions, but exhibited greater capillary density, increased muscle mass and absolute force levels, and performed more work across the 6-min limb function test compared to their wildtype littermates. Conclusion: These results demonstrate the efficacy of the 6-min limb function test to detect differences in the response to HLI where traditional perfusion recovery, capillary density, and muscle strength measures were unable to detect therapeutic differences.

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Section: Exercise Training Interventions Including Home-based Exercisesupporting

confidence: 55%

A 6-minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models

Palzkill,

Tan,

Tice

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…Different groups of researchers have demonstrated the detection of impaired muscle microcirculation and flow reserve by CEUS in PAOD patients compared to healthy individuals. [ 18 - 20 ] A more recent study further established a correlation between symptom severity and the ankle-brachial index (ABI) with CEUS parameters in PAOD patients,[ 21 ] indicating that impaired muscle microcirculation is correlated to the severity of ABI reduction. When comparing limbs with normal ABI in PAOD patients to the healthy population, the muscle microcirculation detected by CEUS was still significantly reduced.…”

Section: R Esults and Discussionsmentioning

confidence: 99%

Update of contrast-enhanced ultrasound in musculoskeletal medicine: Clinical perspectives – A review

et al. 2023

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Contrast-enhanced ultrasound (CEUS) uses an intravascular contrast agent to enhance blood flow signals and assess microcirculation in different parts of the human body. Over the past decade, CEUS has become more widely applied in musculoskeletal (MSK) medicine, and the current review aims to systematically summarize current research on the application of CEUS in the MSK field, focusing on 67 articles published between January 2001 and June 2021 in online databases including PubMed, Scopus, and Embase. CEUS has been widely used for the clinical assessment of muscle microcirculation, tendinopathy, fracture nonunions, sports-related injuries, arthritis, peripheral nerves, and tumors, and can serve as an objective and quantitative evaluation tool for prognosis and outcome prediction. Optimal CEUS parameters and diagnostic cut off values for each disease category remain to be confirmed.

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“…Contrast-enhanced ultrasound and MRI ASL technique demonstrated that hyperemic calf blood flow tended to correlate with the ABI level when the ABI in patients is less than 0.9. 35,36 Our study took a different approach, and evaluated lower leg perfusion in individuals without outflow obstruction (near normal TBI), yet had evidence of tibial artery calcification (ABI ⩾ 1.3). In this unique patient population, we deduced that tibial artery calcification was the main culprit for ABI ⩾ 1.3 since BMI was relatively normal in this cohort, and by itself could not account for the abnormally elevated ABI.…”

Section: Discussionmentioning

confidence: 99%

Pilot study of contrast-free MRI reveals significantly impaired calf skeletal muscle perfusion in diabetes with incompressible peripheral arteries

Zheng

Zayed

et al. 2021

Vasc Med

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Patients with diabetes mellitus (DM) are more likely to have densely calcified lesions in the below-the-knee tibial arteries. However, the relationship between peripheral arterial calcification and local skeletal muscle perfusion has not been explored. Thirty subjects were prospectively recruited into three groups in this pilot study: (1) Non-DM: 10 people without DM; (2) DM, ABI < 1.3: 10 people with DM and normal ankle–brachial index (ABI) (0.9–1.3); and (3) DM, ABI ⩾ 1.3: 10 people with DM and ABI ⩾ 1.3. All subjects underwent calf perfusion measurements at rest and during an isometric plantarflexion contraction exercise within the magnetic resonance imaging (MRI) system. The noncontrast MRI techniques were applied to quantitatively assess skeletal muscle blood flow (SMBF) and oxygen extraction fraction (SMOEF) in medial gastrocnemius and soleus muscles. Both SMBF and SMOEF reserves were calculated as the ratio of the exercise value to the resting value. Exercise SMBF and SMOEF values in the medial gastrocnemius muscle were lower in the two DM groups than in the non-DM group ( p < 0.05). The SMBF reserve in medial gastrocnemius was significantly lower in the DM, ABI ⩾ 1.3 group compared to the DM, ABI < 1.3 group ( p < 0.05). This study demonstrates that people with DM and calcified arteries had lower perfusion in gastrocnemius muscle compared to those without DM and those with DM and a normal ABI.

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Limb Perfusion During Exercise Assessed by Contrast Ultrasound Varies According to Symptom Severity in Patients with Peripheral Artery Disease

Cited by 10 publications

References 32 publications

A 6-minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models

A 6-minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models

Update of contrast-enhanced ultrasound in musculoskeletal medicine: Clinical perspectives – A review

Pilot study of contrast-free MRI reveals significantly impaired calf skeletal muscle perfusion in diabetes with incompressible peripheral arteries

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