phosphocreatine and Peripheral-Vascular-Diseases

Patients with peripheral arterial disease (PAD) suffer from impaired muscle function due to insufficient oxygen supply during exercise, mitochondrial damages, unfavourable muscle fibre type distribution and impaired exercise tolerance. These factors influence the symptoms as well as the quality of life in PAD patients and are closely connected to failures of high-energy phosphate metabolism. At onset of muscle exercise, the mitochondrial capacity cannot match the increased demand. The oxygen supply via blood flow must be increased. Meanwhile, anaerobic glycolysis and internal stores of oxygen like mixed venous blood and myoglobin as well as internal stores of high-energy phosphates like phosphocreatine (PCr) are adducted for the provision of additional adenosine-triphosphate (ATP), which is consumed by the ATPase at the myofibrils in order to fuel muscle contraction. Since the ATP production is insufficient, this phase (anaerobic phase) is characterized by a progressive decrease in PCr, which can be accurately measured by phosphorus 31 magnetic resonance spectroscopy (31p MRS). If the oxygen supply is improved, the mitochondrial capacity can match the increased metabolic demand. This phase is the aerobic phase, which is indicated by a steady-state of PCr hydrolysis. In PAD patients or experimental models of peripheral ischemia, the anaerobic phase is prolonged or does not pass into the aerobic phase resulting in exercise abortion. This review summarizes the results of 31p MRS studies investigating the high-energy phosphate metabolism during ischemic exercise in healthy humans and during ramp or incremental exercise in PAD patients.

Topics: Adenosine Triphosphate; Energy Metabolism; Exercise; Exercise Test; Humans; Magnetic Resonance Angiography; Magnetic Resonance Spectroscopy; Mitochondria, Muscle; Muscle Contraction; Muscle, Skeletal; Oxygen Consumption; Peripheral Vascular Diseases; Phosphocreatine; Phosphorus Isotopes; Time Factors

Patients with peripheral arterial disease (PAD) and aorto-iliac atherosclerotic lesions suffer from a broad range of complaints, such as pain at the hip, the thigh, and calf claudication. The purpose of this study was to investigate the high-energy metabolism in the calf muscle of patients with PAD with isolated aorto-iliac stenoses during incremental plantar flexion exercise.. Using a 1.5 T whole-body magnetic resonance (MR) scanner, 12 patients with PAD with uni- or bilateral aorto-iliac atherosclerotic lesions and 10 healthy male controls underwent serial phosphor-31 MR spectroscopy during incremental exercise at 2, 3, 4, and 5 W. The phosphocreatine (PCr) time constants were calculated for each increment and recovery using a monoexponential model. In the patient group, the run-off resistance was determined on MR angiograms. In both the patients and the controls, the ankle brachial pressure index was measured.. The diseased legs exhibited significantly increased PCr time constants during the second and the third workload increment at 3 and 4 W, but not during the first increment at 2 W and recovery compared with normal controls. Only 3 diseased legs succeeded the last increment at 5 W. We detected significant correlations between the ankle brachial pressure index scores and the PCr time constants when including both the diseased and the control legs. The diseased legs showed a significant correlation with the run-off resistance only during the first increment.. Our study shows that the impairment of muscle metabolism, expressed by prolonged PCr time constants, occurs with greater work intensities in patients with aorto-iliac disease compared with patients with multisegmental PAD, as recently published, whereas our patients collective exhibited normal PCr recovery time constants. Our findings may help to understand variability of clinical symptoms in aorto-iliac PAD.

Topics: Aged; Aorta; Blood Pressure Determination; Constriction, Pathologic; Exercise Test; Female; Humans; Hydrogen-Ion Concentration; Iliac Artery; Leg; Magnetic Resonance Angiography; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Peripheral Vascular Diseases; Phosphocreatine; Radiography

We aimed to investigate the pathophysiology of peripheral arterial disease (PAD) by examining magnetic resonance imaging (MRI) and spectroscopic (MRS) correlates of functional capacity.. Despite the high prevalence, morbidity, and cost of PAD, its pathophysiology is incompletely understood.. Eighty-five patients (age 68 +/- 10 years) with mild-to-moderate PAD (ankle-brachial index 0.69 +/- 0.14) had their most symptomatic leg studied by MRI/MRS. Percent wall volume in the superficial femoral artery was measured with black blood MRI. First-pass contrast-enhanced MRI calf muscle perfusion and (31)P MRS phosphocreatine recovery time constant (PCr) were measured at peak exercise in calf muscle. All patients underwent magnetic resonance angiography (MRA), treadmill testing with maximal oxygen consumption measurement, and a 6-min walk test.. Mean MRA index of number and severity of stenoses was 0.84 +/- 0.68 (normal 0), % wall volume 74 +/- 11% (normal 46 +/- 7%), tissue perfusion 0.039 +/- 0.015 s(-1) (normal 0.065 +/- 0.013 s(-1)), and PCr 87 +/- 54 s (normal 34 +/- 16 s). MRA index, % wall volume, and ankle-brachial index correlated with most functional measures. PCr was the best correlate of treadmill exercise time, whereas calf muscle perfusion was the best correlate of 6-min walk distance. No correlation was noted between PCr and tissue perfusion.. Functional limitations in PAD are multifactorial. As measured by MRI and spectroscopy, atherosclerotic plaque burden, stenosis severity, tissue perfusion, and energetics all play a role. However, cellular metabolism is uncoupled from tissue perfusion. These findings suggest a potential role for therapies that regress plaque, increase tissue perfusion, and/or improve cellular metabolism. (Comprehensive Magnetic Resonance of Peripheral Arterial Disease; NCT00587678).

Topics: Adult; Aged; Exercise Test; Female; Humans; Intermittent Claudication; Leg; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Peripheral Vascular Diseases; Phosphocreatine; Regional Blood Flow

In this study we intend to characterize phosphocreatine (PCr) recovery kinetics with phosphorus-31 ((31)P) magnetic resonance spectroscopy in symptomatic peripheral arterial disease (PAD) patients compared with control subjects and determine the diagnostic value and reproducibility of this parameter.. Due to the inconsistent relationship between flow and function in PAD, novel techniques focused on the end-organ are needed to assess disease severity and measure therapeutic response.. Fourteen normal subjects (5 men, age 45 +/- 14 years) and 20 patients with mild-to-moderate symptomatic PAD (12 men, age 67 +/- 10 years, mean ankle brachial index 0.62 +/- 0.13) were studied. Subjects exercised one leg to exhaustion while supine in a 1.5-T magnetic resonance scanner using a custom-built plantar flexion device. Surface coil-localized, free induction decay acquisition localized to the mid-calf was used. Each 31P spectrum consisted of 25 signal averages at a repetition time of 550 ms. The PCr recovery time constant was calculated by monoexponential fit of PCr versus time, beginning at exercise completion.. Median exercise time was 195.0 s in normal subjects and 162.5 s in PAD patients (p = 0.06). Despite shorter exercise times in patients, the median recovery time constant of PCr was 34.7 s in normal subjects and 91.0 s in PAD patients. Area under the receiver-operating characteristic curve was 0.925 +/- 0.045. Test-retest reliability was excellent.. The PCr recovery time constant is prolonged in patients with symptomatic PAD compared with normal subjects. The method is reproducible and may be useful in the identification of disease. Further study of this parameter's ability to track response to therapy as well as its prognostic capability is warranted.

Topics: Adult; Arteries; Case-Control Studies; Exercise; Female; Humans; Kinetics; Leg; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Peripheral Vascular Diseases; Phosphocreatine; Reproducibility of Results

Methods for measuring mitochondrial activity from 31P magnetic resonance spectroscopy data collected during and after exercise were compared in controls, weight lifters, and peripheral vascular occlusive disease (PVOD) patients. There were trends toward increasing mitochondrial activity during exercise in order from PVOD patients, moderately active controls, highly active controls, to weight lifters. Results from PVOD patients show divergence of some measures due to 1) the non-exponential nature of phosphocreatine recovery, and 2) potential breakdown of [ADP] control of the mitochondria due to lack of oxygen (for Qmax calculation). These results demonstrate the utility of obtaining and directly analyzing high time resolution data rather than assuming monoexponential behavior of metabolite recovery.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Case-Control Studies; Energy Metabolism; Humans; Isometric Contraction; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Mitochondria, Muscle; Muscle, Skeletal; Peripheral Vascular Diseases; Phosphocreatine; Weight Lifting