phosphocreatine and Intermittent-Claudication

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

The aim of the present study was to investigate the possibility of phosphorus magnetic resonance spectroscopy (MR spectroscopy) in the diagnosis of metabolic lesions of skeletal musculature in patients with intermittent claudication syndrome, chronic cardiac failure, and varicose diseases of the lower limbs. Studies included 50 males: 20 patients with intermittent claudication, 10 patients with chronic cardiac failure, and 10 patients with varicose veins. The control group consisted of 10 healthy volunteers. The following measures were determined: the phosphocreatinine index, the intracellular pH in the gastrocnemius muscle, and the half-recovery time for the phosphocreatinine index. The phosphocreatinine index and the pH at rest did not differ between study groups. Isotonic exercise produced no change in the phosphocreatinine index in the control group; patients with intermittent claudication showed a 26.1% decrease, patients with chronic cardiac failure showed an 8% decrease, and patients with varicose veins showed a 25.6% decrease. The only group showing a significant decrease in pH during exercise was the group of patients with intermittent claudication. This group also showed an inverse correlation between the pressure index and the extent of the decrease in the phosphocreatinine index. Thus, MR spectroscopy provides a non-invasive diagnostic method for lesions of energy metabolism in skeletal musculature in patients with deranged peripheral hemodynamics.

Topics: Adult; Aged; Arteriosclerosis Obliterans; Biomarkers; Energy Metabolism; Heart Failure; Humans; Intermittent Claudication; Leg; Magnetic Resonance Imaging; Male; Middle Aged; Muscle, Skeletal; Phosphocreatine; Phosphorus; Reference Values; Varicose Veins

Decreased oxygen supply is generally accepted as the primary cause of muscle dysfunction in patients with peripheral arterial occlusive disease (PAOD) and intermittent claudication, although reported morphologic changes in the mitochondria of claudicating muscle suggest that impaired energy utilization may also play a role. With the measurement of the phosphate-rich compounds of muscle energy metabolism (adenosinetriphosphate [ATP], adenosinediphosphate [ADP], and phosphocreatine [PCr]) and pH, phosphorus P 31 magnetic resonance spectroscopy ((31)P MRS) provides a unique, noninvasive method to investigate this hypothesis further.. Calf muscle bioenergetics were studied in 12 men with moderate claudication (ankle-brachial index >/=0.5 and .5, Pearson moment correlation).. Phosphorus 31 MRS provides the first direct evidence of defective energy metabolism in the mitochondria of claudicating calf muscle. This defect appears to be independent of both arterial flow and the severity of occlusive disease in patients with mild to moderate claudication. Coupled with documented ultrastructural and DNA abnormalities in the mitochondria of claudicating skeletal muscle, these data provide evidence for a secondary cause of muscle dysfunction in intermittent claudication.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Case-Control Studies; Energy Metabolism; Exercise Test; Humans; Intermittent Claudication; Magnetic Resonance Spectroscopy; Male; Mitochondria, Muscle; Muscle, Skeletal; Phosphocreatine

Energy status and metabolism in skeletal muscle of nine patients with peripheral arterial disease and suffering from intermittent claudication were evaluated using 31phosphorus magnetic resonance spectroscopy (MRS) before and after treatment for 3 months with propionyl-L-carnitine (PLC; 2 g/day p.o.). Maximum walking distance (MWD) was assessed on a standard treadmill (4 km/h, zero incline). For the group as a whole 31P MRS results did not change significantly with PLC. Although MWD increased by a mean of 36%, this change did not reach significance. However, when these variables were assessed with respect to the change in MWD, there were significant differences between those who increased MWD by > 30% (responders, R; n = 5) and those who did not (nonresponders, NR; n = 4). Compared with pretreatment values, during exercise the decrease in muscle pH in R relative to the decrease in phosphocreatine was less after PLC (p = 0.04). After exercise there was a significant inverse correlation between the changes in recovery half-time (t1/2) for phosphocreatine and in MWD (r = -0.91, p = 0.01). With PLC, Vmax increased in R (p = 0.04), but not in NR. For the patient group as a whole, the changes in Vmax and MWD correlated positively (r = 0.90, p = 0.01). This study helps to identify the changes in muscle metabolism that correlate with changes in exercise performance, and may accompany treatment with PLC.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adult; Aged; Aged, 80 and over; Carnitine; Energy Metabolism; Female; Humans; Intermittent Claudication; Leg; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Phosphocreatine; Phosphorus; Walking

Thirty-seven men with angiography or ultrasound confirmed peripheral arterial occlusive disease were divided into two groups. Group 1 included 24 patients treated with one daily infusion of 10 g of phosphocreatine in 200 ml of solvent for 10 days. Group 2 included 13 patients who were given 0.9% NaCl in the same scheme. Groups were comparable in: duration of intermittent claudication, maximal walking distance, Ketle index, cholesterol, triglycerides, frequency of ischemic heart disease, hypertension, diabetes, smoking. Patients were examined 4 times: before starting, on second day, after treatment period, and 1 month after. Treadmill-test; ADP-, PAF-, 5-HT-induced platelet aggregation; D-dimer; PAI-1 activity; blood viscosity at high and low shear rate; hematocrit were performed. After treatment maximal walking distance significantly increased in patients of Group 1. Mechanisms of this effects include positive influence of phosphocreatine on platelet aggregation, blood rheology, coagulation and fibrinolytic systems.

Topics: Blood Flow Velocity; Fibrinolysis; Humans; Injections, Intravenous; Intermittent Claudication; Male; Middle Aged; Phosphocreatine; Platelet Aggregation; Walking

We have used 31phosphorus magnetic resonance spectroscopy (31P-MRS) to study foot muscle metabolism in patients with peripheral vascular disease. Sixteen patients with calf claudication, 32 patients with rest pain and 13 control subjects had spectra collected from the foot muscle, Extensor digitorum brevis, ankle pressures measured and, in most cases, transcutaneous O2 and CO2 recordings made over the foot. The intracellular pH and the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) obtained from the MR spectra were significantly higher (p less than 0.005 and p less than 0.02, respectively) in the muscle of patients with rest pain and were particularly high in those with gangrene or ulceration. Ankle pressures and transcutaneous O2 and CO2 measurements failed to distinguish those patients with advanced peripheral ischaemia. These results suggest that MRS measurements of metabolic changes in foot muscle are useful in the detection and quantitation of significant distal ischaemia.

Topics: Aged; Blood Gas Monitoring, Transcutaneous; Female; Foot; Humans; Intermittent Claudication; Ischemia; Magnetic Resonance Spectroscopy; Male; Muscles; Phosphates; Phosphocreatine

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

The treadmill exercise test is the most important examination of the functional ability of patients with intermittent claudication or leg pain during exercise, but it does not provide any metabolic information in the calf muscle. The purpose of this study was to investigate the high-energy metabolism in the calf muscle during incremental progressive plantar flexion exercise of a selected peripheral arterial disease (PAD) patient group.. Using a 1.5-T whole-body magnetic resonance scanner, 17 male patients with PAD who had 1 symptomatic and 1 asymptomatic leg and 9 healthy male controls underwent serial phosphor 31 (31P) magnetic resonance spectroscopy during incremental exercise at 2, 3, 4, and 5 W. Furthermore, magnetic resonance angiography was performed, and the ankle-brachial pressure index was determined in the patient group. The runoff resistance (ROR) was separately assessed in each patient's leg.. The symptomatic legs exhibited significantly increased phosphocreatine (PCr) time constants during the first three workload increments (2-4 W) and the recovery phase compared with the asymptomatic legs and the normal controls. Only two symptomatic legs reached the last increment at 5 W. Compared with the normal controls, the asymptomatic legs showed significantly increased PCr time constants only at 5 W. In the patient group, we detected significant correlations between the PCr time constants and the ROR, as well as the ankle-brachial pressure index. Moreover, the symptomatic legs presented significantly lower PCr levels and pH values at the end of exercise compared with the asymptomatic and control legs.. Our study shows that muscle function in PAD patients can be objectively quantified with the help of 31P magnetic resonance spectroscopy and correlates significantly with hemodynamic parameters such as ROR and ankle-brachial pressure index. Consequently, 31P magnetic resonance spectroscopy seems to be a useful method to monitor the muscle function of PAD patients for evaluation of established therapies or new therapeutic strategies during research trials.

Topics: Aged; Arterial Occlusive Diseases; Energy Metabolism; Exercise; Exercise Test; Female; Hemodynamics; Humans; Hydrogen-Ion Concentration; Intermittent Claudication; Leg; Magnetic Resonance Angiography; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Phosphocreatine; Reference Values; Statistics as Topic; Vascular Resistance

In order to assess the acute metabolic effects of an intra-arterial infusion of nucleotide-nucleoside-mixture (NNM), 31P-mr-spectroscopy at the site of m. gastrocnemius and metabolite determinations from blood of the femoral artery and vein were carried out in 10 patients with PAOD stage II during ergometric calf exercise to the claudication pain limit. The spectroscopic measurements revealed a greater exercise-induced fall of PCr and a higher increase of Pi in calf muscles during supply of NNM compared with control ergometry. Post-exercise recovery of PCr was distinctly delayed during infusion of NNM. The anaerobic production of energy, however, was sufficient to maintain the ATP concentration to the same extent as under control ergometry. On the other hand, intramuscular lactate acidosis developed to a lower degree with NNM infusion than without NNM. A reduced muscular release of lactate, pyruvate, ammonia and alanine followed from the evaluation of the arteriovenous balance of these metabolites in the femoral vessels indicating a favourable global metabolic effect of NNM infusion in the extremity. The apparent contradiction in the spectroscopic and analytic-biochemical findings can be explained by local blood shunts induced by maximum vasodilation. Noninvasive mr-spectroscopy allows to detect directly and continuously the metabolic impact of ischemia in the calf muscles afflicted by arterial occlusion, whereas the metabolite concentrations in femoral blood are altered by afflux from non-ischemic areas. The known clinical benefit of frequently repeated intra-arterial infusions of NNM is thought to be due to an expansion of collateral circulation and to a favourable influence on endothelial functions.

Topics: Adenosine Triphosphate; Arterial Occlusive Diseases; Energy Metabolism; Exercise Test; Humans; Infusion Pumps; Intermittent Claudication; Ischemia; Leg; Magnetic Resonance Spectroscopy; Male; Muscles; Nucleosides; Nucleotides; Phosphates; Phosphocreatine

Using 31P nuclear magnetic resonance spectroscopy of the calf muscle, the authors studied patients with peripheral arterial occlusive disease. They studied PCr depletion and intracellular pH during aerobic exercise in patients and controls. The phosphocreatine (PCr) index ([PCr]/([PCr] + [Pi])) at rest was correlated with blood flow measured by plethysmography. During aerobic exercise a greater decrease in pH was obtained in patients (p < 0.03). They also studied the work necessary to reach a PCr index = 0.5 during ischemic exercise. This workload was lower in patients than in controls: 32.99 +/- 3.04 J vs 58.89 +/- 8.55 J, p < 0.05. After vasodilator therapy the workload was improved in patients: 32.99 +/- 3.04 J vs 38.85 +/- 3.54 J, p < 0.05. These results suggest that therapy resulted in improved tissue perfusion in patients.

Topics: Arterial Occlusive Diseases; Exercise; Humans; Hydrogen-Ion Concentration; Intermittent Claudication; Ischemia; Leg; Magnetic Resonance Spectroscopy; Middle Aged; Oxidative Phosphorylation; Phosphocreatine; Phosphorus Radioisotopes; Vasodilator Agents

Topics: Adenosine Triphosphate; Arterial Occlusive Diseases; Diabetic Angiopathies; Energy Metabolism; Humans; Intermittent Claudication; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscles; Phosphates; Phosphocreatine; Prospective Studies

Phosphorus NMR spectrometry allows non-invasive exploration in vivo of certain aspects of muscle energy metabolism. A study was conducted in 10 healthy volunteers and 12 patients with lower limb affections (stage II claudication) to define a precise methodology and to discuss perspectives offered by this new method, in the light of preliminary findings. Changes with time of amplitude of peaks of phosphocreatine (Pcr), inorganic phosphorus (Pi) and ATP, and of intracellular pH, showed that recovery of 80% of resting value of the ratio Pcr/Pi + Pcr after quantified exercise is a very discriminatory parameter correlated with severity of arteriographic findings in patients with claudication.

Topics: Energy Metabolism; Humans; Intermittent Claudication; Leg; Magnetic Resonance Spectroscopy; Muscles; Phosphates; Phosphocreatine

31P in-vivo spectroscopy was performed by a 1.5-tesla whole-body MR system. The 31P spectrum for the calf muscle in a patient with arteriosclerosis obliterans having intermittent claudication was obtained every two minutes. When the spectrum after the workload was compared with that at rest, an increase in inorganic phosphate (Pi) and a decrease in phosphocreatine (PCr) were observed, resulting in a strong decrease in the PCr/Pi ratio. This method can measure the ischemic and recovery stages of energy metabolism in skeletal muscle noninvasively and continuously in addition to magnetic resonance imaging.

Topics: Aged; Angiography; Arteriosclerosis Obliterans; Energy Metabolism; Humans; Intermittent Claudication; Leg; Magnetic Resonance Spectroscopy; Male; Muscles; Phosphates; Phosphocreatine; Phosphorus Radioisotopes; Radionuclide Imaging

Eleven men with claudication and ten control subjects had calf muscle metabolism studied at rest and during exercise and the subsequent recovery period by 31P nuclear magnetic resonance (n.m.r.) spectroscopy. The muscle of patients with severe claudication had a significantly greater depletion of phosphocreatine and fall in pH during exercise and a slower recovery of phosphocreatine and pH after exercise. The muscle of patients with both mild and severe disease had slower rates of ADP recovery after exercise than that of control subjects. Surgical correction of the associated arterial stenosis abolished claudication and led to correction of the metabolic abnormalities in two patients. Claudication pain was not related to intracellular pH or concentration of phosphorus-containing metabolites. Energy production via oxidative metabolism is impaired but glycolysis may be increased in the calf muscle of patients with intermittent claudication.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adult; Aged; Humans; Hydrogen-Ion Concentration; Intermittent Claudication; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscles; Phosphocreatine

In addition to the determination of the presenting symptom of patients with peripheral vascular occlusive disease, evaluation of these patients may include the noninvasive measurements of ankle/arm pressure ratio, limb blood flow, and treadmill testing to evaluate the severity of the reduction in blood flow. We have included metabolic studies to assess the effect of this reduced blood flow in patients with stable intermittent claudication (n = 20), and with end-stage ischemia (night and rest pain) (n = 11), and in a control group without vascular disease (n = 8). No correlations were found between the resting limb blood flow, ankle/arm pressure ratios, maximum walking distance, and stated walking distance for the patients with stable claudication. Although the oxygen consumption was reduced only in the patients with end-stage ischemia, the percent oxygen extraction was increased to the same level in the patients with stable claudication and those with end-stage ischemia. Intramuscular stores of high-energy phosphates and glycogen were maintained in all groups with the lactate/pyruvate ratio increased only in the patients with end-stage ischemia. The complex interrelationships between the rate and distribution of blood flow with exercise and enzyme adaptation in patients with vascular disease make current resting hemodynamic and metabolic evaluations a poor reflection of the severity of the clinical condition within each patient group. Therefore laboratory testing may offer no advantage over clinical presentation in the overall evaluation of these patients.

Topics: Adenosine Triphosphate; Adult; Aged; Blood Pressure; Glycogen; Humans; Intermittent Claudication; Ischemia; Lactates; Lactic Acid; Leg; Middle Aged; Muscles; Oxygen Consumption; Phosphocreatine; Pyruvates; Pyruvic Acid; Regional Blood Flow

Nine patients with chronic iliac vein obstruction and venous claudication were investigated. Intramuscular pressure was measured in the anterior tibial and the deep posterior compartments in both legs at rest and during exercise. The pressures were significantly higher in the leg with iliac vein obstruction (39 +/- 10 mm Hg) than in the contralateral leg (26 +/- 12 mm Hg) at rest as well as during exercise (60 +/- 16 mm Hg and 41 +/- 15 mm Hg, respectively) in the deep posterior compartment. Similar changes were observed in the anterior tibial compartment. Muscle water content was higher (P less than 0.01) in the obstructed leg and contributes to the explanation for the high intramuscular pressure in this leg. Muscle blood flow, adenosine triphosphate, phosphocreatine, and lactate were determined in the gastrocnemius muscles at rest and at exercise. Muscle blood flow, measured with the 133xenon clearance technique, was lower in the obstructed leg (17.5 ml/min, 100 gm) than in the control leg (28.1 ml/min, 100 gm) during exercise. Lactate increased more (P less than 0.05) in the obstructed leg. It is suggested that pain in venous claudication is caused by the high intramuscular pressure, and therefore fasciotomy may be useful in the treatment of this disorder.

Topics: Adenosine Triphosphate; Adolescent; Adult; Aged; Blood Pressure; Chronic Disease; Female; Humans; Iliac Vein; Intermittent Claudication; Lactates; Lactic Acid; Leg; Male; Middle Aged; Muscles; Phosphocreatine; Venous Insufficiency; Venous Pressure

Incomplete ischaemia was caused by clamping the aorta during reconstructive vascular surgery. After restoration of the blood flow extensive metabolic and morphological changes in the muscle tissue were observed. The adenylate (ATP + ADP + AMP) and the creatine (PCr + Cr) pools declined 30-40% and the energy charge of the adenine nucleotides dropped significantly. The metabolic pool changes were closely related to the changes in the lactate/pyruvate ratios. Morphological signs of membrane disturbances, such as fibre oedema and swelling of mitochondria, were seen in many muscle fibres 30 min after declamping. 5 days postoperatively, a number of mitochondrial abnormalities were observed and fibre regeneration was seen in places. The relative number of Type 2 fibres and the width of the capillary lumen were both related to the decrease of the metabolic parameters. Thus, the metabolic state and the fine structure of the incompletely ischaemic muscle were closely related to each other. The amount of Type 2 fibres seemed to be of special importance for the patho-physiological events in intermittently ischaemic muscle fibres.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Adult; Aged; Constriction; Female; Humans; Intermittent Claudication; Ischemia; Lactates; Lactic Acid; Leg; Male; Middle Aged; Mitochondria, Muscle; Muscles; Phosphocreatine; Pyruvates; Pyruvic Acid

A study was carried out in 13 patients with stabilized occlusive arterial disease to assess the effect of treatment with creatine phosphate (800 mg/day for 12 days) on walking distance to onset of disabling pain and on haemodynamic parameters (Winsor Index and calf arterial blood flow after ischaemia). Before treatment, patients had daily exercise for 12 days on a treadmill to plateau walking distance increase due to exercise. The results showed a further significant increase in walking distance after treatment, and a significant increase in peak reactive hyperaemia in all but 2 patients. The possible mechanisms of the effects of creatine phosphate are discussed.

Topics: Adult; Aged; Hemodynamics; Humans; Intermittent Claudication; Leg; Male; Middle Aged; Phosphocreatine; Physical Exertion; Regional Blood Flow

Topics: Adenosine Triphosphate; Adult; Exercise Test; Glycogen; Humans; Intermittent Claudication; Lactates; Leg; Male; Middle Aged; Muscles; Oxygen Consumption; Phosphocreatine; Physical Exertion; Regional Blood Flow