phosphocreatine and Peripheral-Arterial-Disease

We hypothesized that percutaneous intervention in the affected lower extremity artery would improve calf muscle perfusion and cellular metabolism in patients with claudication and peripheral artery disease (PAD) as measured by magnetic resonance imaging (MRI) and spectroscopy (MRS). Ten patients with symptomatic PAD (mean ± SD: age 57 ± 9 years; ankle-brachial index (ABI) 0.62 ± 0.17; seven males) were studied 2 months before and 10 months after lower extremity percutaneous intervention. Calf muscle phosphocreatine recovery time constant (PCr) in the revascularized leg was measured by (31)P MRS immediately after symptom-limited exercise on a 1.5-T scanner. Calf muscle perfusion was measured using first-pass gadolinium-enhanced MRI at peak exercise. A 6-minute walk and treadmill test were performed. The PCr recovery time constant improved significantly following intervention (91 ± 33 s to 52 ± 34 s, p < 0.003). Rest ABI also improved (0.62 ± 0.17 to 0.93 ± 0.25, p < 0.003). There was no difference in MRI-measured tissue perfusion or exercise parameters, although the study was underpowered for these endpoints. In conclusion, in this pilot study, successful large vessel percutaneous intervention in patients with symptomatic claudication, results in improved ABI and calf muscle phosphocreatine recovery kinetics.

Topics: Adult; Aged; Aged, 80 and over; Ankle Brachial Index; Exercise; Exercise Test; Female; Humans; Intermittent Claudication; Leg; Magnetic Resonance Angiography; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Peripheral Arterial Disease; Phosphocreatine; Pilot Projects; Regional Blood Flow; Vascular Surgical Procedures

We hypothesized that low-density lipoprotein (LDL) reduction regardless of mechanism would improve calf muscle perfusion, energetics, or walking performance in peripheral arterial disease (PAD) as measured by magnetic resonance imaging and magnetic resonance spectroscopy.. Statins improve cardiovascular outcome in PAD, and some studies suggest improved walking performance.. Sixty-eight patients with mild to moderate symptomatic PAD (age 65 ± 11 years; ankle-brachial index [ABI] 0.69 ± 0.14) were studied at baseline and annually for 2 years after beginning simvastatin 40 mg (n = 20) or simvastatin 40 mg/ezetimibe 10 mg (n = 18) if statin naïve, or ezetimibe 10 mg (n = 30) if taking a statin. Phosphocreatine recovery time was measured by (31)P magnetic resonance spectroscopy immediately after symptom-limited calf exercise on a 1.5-T scanner. Calf perfusion was measured using first-pass contrast-enhanced magnetic resonance imaging with 0.1 mM/kg gadolinium at peak exercise. Gadolinium-enhanced magnetic resonance angiography was graded. A 6-min walk and a standardized graded Skinner-Gardner exercise treadmill test with peak Vo(2) were performed. A repeated-measures model compared changes over time.. LDL reduction from baseline to year 2 was greater in the simvastatin 40 mg/ezetimibe 10 mg group (116 ± 42 mg/dl to 56 ± 21 mg/dl) than in the simvastatin 40 mg group (129 ± 40 mg/dl to 90 ± 30 mg/dl, p < 0.01). LDL also decreased in the ezetimibe 10 mg group (102 ± 28 mg/dl to 79 ± 27 mg/dl, p < 0.01). Despite this, there was no difference in perfusion, metabolism, or exercise parameters between groups or over time. Resting ABI did improve over time in the ezetimibe 10 mg group and the entire study group of patients.. Despite effective LDL reduction in PAD, neither tissue perfusion, metabolism, nor exercise parameters improved, although rest ABI did. Thus, LDL lowering does not improve calf muscle physiology or functional capacity in PAD. (Comprehensive Magnetic Resonance of Peripheral Arterial Disease; NCT00587678).

Topics: Aged; Anticholesteremic Agents; Azetidines; Cholesterol, LDL; Energy Metabolism; Exercise Test; Exercise Tolerance; Ezetimibe; Female; Humans; Leg; Magnetic Resonance Angiography; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Peripheral Arterial Disease; Phosphocreatine; Simvastatin

Peripheral artery disease (PAD) results in exercise-induced ischemia in leg muscles.. Patients with PAD and age-matched normal subjects were imaged at 3T with a transmit-receive coil around the calf. Four CEST mages were acquired over 24-second intervals. The subjects then performed plantar flexion exercise on a magnetic resonance imaging-compatible ergometer until calf exhaustion. Twenty-five CEST images were obtained at end exercise. Regions of interest were drawn around individual muscle groups, and (CEST. Thirty-five patients with PAD (31 male, age 66±8 years) and 29 controls (11 male, age 63±8 years) were imaged with CEST. The CEST. CEST is a magnetic resonance imaging method that can distinguish energetics in patients with PAD from age-matched normal subjects on a per muscle group basis. CEST agrees reasonably well with the gold standard

Topics: Aged; Humans; Leg; Magnetic Resonance Imaging; Male; Middle Aged; Muscle, Skeletal; Peripheral Arterial Disease; Phosphocreatine

To identify differences in postexercise phosphocreatine (PCr) recovery, an index of mitochondrial function, in diabetic patients with and without lower extremity complications.. We enrolled healthy control subjects and three groups of patients with type 2 diabetes mellitus: without complications, with peripheral neuropathy, and with both peripheral neuropathy and peripheral arterial disease. We used magnetic resonance spectroscopic measurements to perform continuous measurements of phosphorous metabolites (PCr and inorganic phosphate [Pi]) during a 3-minute graded exercise at the level of the posterior calf muscles (gastrocnemius and soleus muscles). Micro- and macrovascular reactivity measurements also were performed.. The resting Pi/PCr ratio and PCr at baseline and the maximum reached during exercise were similar in all groups. The postexercise time required for recovery of Pi/PCr ratio and PCr levels to resting levels, an assessment of mitochondrial oxidative phosphorylation, was significantly higher in diabetic patients with neuropathy and those with both neuropathy and peripheral arterial disease (P < .01 for both measurements). These two groups also had higher levels of tumor necrosis factor-α (P < .01) and granulocyte colony-stimulating factor (P < .05). Multiple regression analysis showed that only granulocyte colony-stimulating factor, osteoprotegerin, and tumor necrosis factor-α were significant contributing factors in the variation of the Pi/PCr ratio recovery time. No associations were observed between micro- and macrovascular reactivity measurements and Pi/PCr ratio or PCr recovery time.. Mitochondrial oxidative phosphorylation is impaired only in type 2 diabetes mellitus patients with neuropathy whether or not peripheral arterial disease is present and is associated with the increased proinflammatory state observed in these groups.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Exercise; Female; Granulocyte Colony-Stimulating Factor; Humans; Inflammation Mediators; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mitochondria; Muscle Contraction; Muscle, Skeletal; Osteoprotegerin; Oxidative Phosphorylation; Peripheral Arterial Disease; Phosphocreatine; Time Factors; Tumor Necrosis Factor-alpha

Topics: Female; Humans; Leg; Male; Muscle, Skeletal; Peripheral Arterial Disease; Phosphocreatine; Vascular Surgical Procedures