Delayed Calf Muscle Phosphocreatine Recovery After Exercise Identifies Peripheral Arterial Disease

Isbell, David C.; Berr, Stuart S.; Toledano, Alicia Y.; Epstein, Frederick H.; Meyer, Craig H.; Rogers, W. Todd; Harthun, Nancy L.; Hagspiel, Klaus D.; Weltman, Arthur; Kramer, Christopher M.

doi:10.1016/j.jacc.2005.12.069

Cited by 69 publications

(87 citation statements)

References 39 publications

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“…A total of 37% depletion of PCr was observed with exercise with a recovery rate constant ( k PCr) of 20.6 ms −1 . These findings are consistent with reports from similar populations 16, 26. The average ABI was 1.16±0.08, with 82 participants (22%) having ABI of 0.90 to 1.10.…”

Section: Resultssupporting

confidence: 92%

Lower Mitochondrial Energy Production of the Thigh Muscles in Patients With Low‐Normal Ankle‐Brachial Index

AlGhatrif

Zane

Oberdier

et al. 2017

JAHA

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BackgroundLower muscle mitochondrial energy production may contribute to impaired walking endurance in patients with peripheral arterial disease. A borderline ankle‐brachial index (ABI) of 0.91 to 1.10 is associated with poorer walking endurance compared with higher ABI. We hypothesized that in the absence of peripheral arterial disease, lower ABI is associated with lower mitochondrial energy production.Methods and ResultsWe examined 363 men and women participating in the Baltimore Longitudinal Study of Aging with an ABI between 0.90 and 1.40. Muscle mitochondrial energy production was assessed by post‐exercise phosphocreatine recovery rate constant (kPCr) measured by phosphorus magnetic resonance spectroscopy of the left thigh. A lower post‐exercise phosphocreatine recovery rate constant reflects decreased mitochondria energy production.The mean age of the participants was 71±12 years. A total of 18.4% had diabetes mellitus and 4% were current and 40% were former smokers. Compared with participants with an ABI of 1.11 to 1.40, those with an ABI of 0.90 to 1.10 had significantly lower post‐exercise phosphocreatine recovery rate constant (19.3 versus 20.8 ms−1, P=0.015). This difference remained significant after adjusting for age, sex, race, smoking status, diabetes mellitus, body mass index, and cholesterol levels (P=0.028). Similarly, post‐exercise phosphocreatine recovery rate constant was linearly associated with ABI as a continuous variable, both in the ABI ranges of 0.90 to 1.40 (standardized coefficient=0.15, P=0.003) and 1.1 to 1.4 (standardized coefficient=0.12, P=0.0405).ConclusionsAn ABI of 0.90 to 1.10 is associated with lower mitochondrial energy production compared with an ABI of 1.11 to 1.40. These data demonstrate adverse associations of lower ABI values with impaired mitochondrial activity even within the range of a clinically accepted definition of a normal ABI. Further study is needed to determine whether interventions in persons with ABIs of 0.90 to 1.10 can prevent subsequent functional decline.

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Section: Resultssupporting

confidence: 92%

Lower Mitochondrial Energy Production of the Thigh Muscles in Patients With Low‐Normal Ankle‐Brachial Index

AlGhatrif

Zane

Oberdier

et al. 2017

JAHA

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“…Correlation of clinical efficacy with changes in tissue blood flow at peak exercise will help us to better understand our current treatment approach and will be critical in the development and validation of new therapeutic strategies for PAD patients. Because the skeletal muscle does not remain a passive bystander during the development of PAD, association of tissue perfusion with noninvasive measures of skeletal muscle metabolism and cellular energetics will also be important in understanding patient symptoms, performance measures, and clinical outcomes (40).…”

Section: Potential Applications and Future Directionsmentioning

confidence: 99%

Calf muscle perfusion at peak exercise in peripheral arterial disease: Measurement by first‐pass contrast‐enhanced magnetic resonance imaging

Isbell

Epstein

Zhong

et al. 2007

Magnetic Resonance Imaging

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Purpose:To develop a contrast-enhanced magnetic resonance (MR) technique to measure skeletal muscle perfusion in peripheral arterial disease (PAD). Materials and Methods:A total of 11 patients (age ϭ 61 Ϯ 11 years) with mild to moderate symptomatic PAD (anklebrachial index [ABI] ϭ 0.75 Ϯ 0.08) and 22 normals were studied using an MR-compatible ergometer. PAD and normal max (Nl max ; N ϭ 11) exercised to exhaustion. Nl low (N ϭ 11) exercised to the same workload achieved by PAD. At peak exercise, 0.1 mm/kg of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) was infused at 3-4 cm 3 / second followed by a saline flush at the same rate. A dualcontrast gradient echo (GRE) sequence enabled simultaneous acquisition of muscle perfusion and arterial input function (AIF). The perfusion index (PI) was defined as the slope of the time-intensity curve (TIC) in muscle divided by the arterial TIC slope. Results Conclusion:Peak-exercise measurement of lower limb perfusion with dual-contrast, first-pass MR distinguishes PAD from normals. This method may be useful in the study of novel therapies for PAD.

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“…Because the skeletal muscle does not remain a passive bystander during the development of PAD, association of tissue perfusion with noninvasive measures of skeletal muscle metabolism, and cellular energetics will also be important in understanding patient symptoms, performance measures, and clinical outcomes. 16 31 P MRS has a number of potential applications in the PAD population. The relationship between PCr recovery kinetics and clinical events involving the lower limbs deserves further exploration in a larger cohort of patients.…”

Section: First-pass Contrast-enhanced Calf Muscle Perfusion At Peak Ementioning

confidence: 99%

“…13 Our group has performed a series of studies to validate and assess the potential use of these measures in PAD. [14][15][16] …”

mentioning

confidence: 99%

Peripheral Arterial Disease Assessment

Kramer

2007

Topics in Magnetic Resonance Imaging

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Delayed Calf Muscle Phosphocreatine Recovery After Exercise Identifies Peripheral Arterial Disease

Cited by 69 publications

References 39 publications

Lower Mitochondrial Energy Production of the Thigh Muscles in Patients With Low‐Normal Ankle‐Brachial Index

Lower Mitochondrial Energy Production of the Thigh Muscles in Patients With Low‐Normal Ankle‐Brachial Index

Calf muscle perfusion at peak exercise in peripheral arterial disease: Measurement by first‐pass contrast‐enhanced magnetic resonance imaging

Peripheral Arterial Disease Assessment

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