Phosphocreatine Time Constant Research Articles

Insulin Resistance, Hyperinsulinemia, and Mitochondria Dysfunction in Nonobese Girls With Polycystic Ovarian Syndrome.

Objective:Obese girls with polycystic ovarian syndrome (PCOS) have decreased insulin sensitivity (IS), muscle mitochondrial dysfunction and increased liver fat, which may contribute to their increased risk for type 2 diabetes. Less is known regarding normal-weight girls with PCOS.Methods:Normal-weight girls with PCOS [n =18, age 15.9 ± 1.8 years, body mass index (BMI) percentile 68 ± 18] and normal-weight controls (NWC; n = 20; age 15.0 ± 2.1 years, BMI percentile 60 ± 21) were studied. Tissue-specific IS was assessed with a four-phase hyperinsulinemic-euglycemic clamp with isotope tracers and a 2-hour oral glucose tolerance test (OGTT). Hepatic fat was determined using magnetic resonance imaging. Postexercise muscle mitochondrial function was assessed with 31P MR spectroscopy.Results:Both groups had similar demographics, anthropomorphics, physical attributes, habitual physical activity levels and fasting laboratory values, except for increased total testosterone and DHEAS in PCOS. Clamp-assessed peripheral IS was lower in PCOS (10.4 ± 2.4 mg/kg/min vs 12.7 ± 2.1; P = 0.024). The 120-minute OGTT insulin and glucose concentrations were higher in PCOS (114 IU/mL ± 26 vs 41 ± 25, P = <0.001 and 119 ± 22 mg/dL vs 85 ± 23, P = 0.01, respectively). Muscle mitochondrial ADP and phosphocreatine time constants were slower in PCOS. Despite a higher percentage liver fat in PCOS, hepatic IS was similar between groups, as was adipose IS.Conclusions:Normal-weight girls with PCOS have decreased peripheral IS and muscle mitochondrial dysfunction, abnormal glucose disposal, relative postprandial hyperinsulinemia, and increased hepatic fat compared to NWC. Despite a normal BMI, multiple aspects of metabolism appear altered in normal-weight girls with PCOS.

Phosphocreatine Kinetics in the Calf Muscle of Patients with Bilateral Symptomatic Peripheral Arterial Disease during Exhaustive Incremental Exercise

To investigate the relationship between the atherosclerotic lesion load determined on magnetic resonance angiography (MRA) and phosphocreatine (PCr) kinetics during incremental, exhaustive calf exercise in patients with bilateral, symptomatic peripheral arterial disease (PAD). Using a 1.5 Tesla MR scanner, 26 patients with bilateral symptomatic PAD and 24 healthy male controls underwent serial phosphorus-31 MR spectroscopy (31P MRS) during incremental exercise at 2, 3, 4, and 5 Watts. For each increment and recovery, PCr time constants, amplitudes of PCr changes and pH values were calculated from the MR spectra. In patients, the run-off resistance (ROR) was determined on MRA. The patients exhibited significantly (p <or= 0.002) increased PCr time constants at the first (36.7, 13.8-360.3 vs. 22.9, 9.2-60.7 s), at the second (68.1, 4.2-757.2 vs. 18.3, 5.2-57.6 s), at the third (65.3, 14.7-277.7 vs. 29.0, 4.48-97.2 s), the fourth increment (64.1, 34.2-548.8 vs. 34.6, 4.9-106.2 s), and during recovery (53.2, 11.1-353.2 vs. 41.4, 15.1-122.4 s) compared to the normal controls. The PCr on-kinetics during the increments correlated significantly with the pH levels (r= -0.39 to -0.66, p <or= 0.005) at the end of the corresponding increments, but not with the RORs. The correlation between PCr on-kinetics and end-increment pH values might indicate remodelling processes within the muscle that probably affect mitochondrial performance, diffusion of oxygen, and muscle fiber distribution. These parameters could be improved by exercise training.

High-energy phosphate metabolism in the calf muscle of healthy humans during incremental calf exercise with and without moderate cuff stenosis

It is known that the relevance of a peripheral stenosis for muscle function increases with exercise. Our intention was to investigate the impact of a moderate cuff stenosis (CS) at 120 mmHg of the superficial femoral artery on high-energy phosphate (HEP) metabolism during isotonic, incremental calf exercise. Serial phosphorus 31 magnetic resonance spectroscopy (31P MRS) and velocity-encoded phase-contrast MR imaging (VEPC MRI) were carried out in each leg of ten healthy male volunteers. Each leg underwent four increments of calf exercise (2, 3, 4 and 5 W) followed by recovery during separate exercise sessions with and without a CS at 120 mmHg. The serial 31P MRS measurements had a time resolution of 10 s. VEPC MRI was performed at the end of each increment during separate sessions. During all increments, we detected significant differences (P < 0.05) in the phosphocreatine (PCr) time constants and the amount of PCr hydrolysis between the sessions without and with CS. Regarding the time courses of the PCr, inorganic phosphate (Pi) and pH level, we observed significant differences (P < 0.002) during exercise and recovery. During both conditions, the end-increment PCr levels as well as blood flow correlated significantly with the mechanical power. The PCr time constants during exercise significantly correlated with the intramuscular pH, but not with blood flow or mechanical power. However, the PCr recovery time constants correlated significantly with blood flow and end-exercise pH. Our study shows that reduction of blood flow due to a peripheral stenosis results in a prolongation of PCr time constants, decreased PCr and pH level as well as increased Pi level during exercise. We believe that 31P MRS during incremental exercise might provide additional information for assessing the relevance of a peripheral stenosis and its impact on muscle function.

High-Energy Phosphate Metabolism During Calf Ergometry in Patients With Isolated Aorto-Iliac Artery Stenoses

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.

High-energy phosphate metabolism during incremental calf exercise in patients with unilaterally symptomatic peripheral arterial disease measured by phosphor 31 magnetic resonance spectroscopy

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.

Simultaneous in vivo measurements of HbO2 saturation and PCr kinetics after exercise in normal humans

Simultaneous measurements of phosphocreatine (PCr) and oxyhemoglobin (HbO2) saturation were made during recovery from exercise in calf muscles of five male subjects. PCr was measured using magnetic resonance spectroscopy in a 2.0-T 78-cm-bore magnet with a 9-cm-diam surface coil. Relative HbO2 saturation was measured as the difference in absorption of 750- and 850-nm light with use of near-infrared spectroscopy. The light source and detectors were 3 cm apart. Exercise consisted of isokinetic plantar flexion in a supine position. Two 5-min submaximal protocols were performed with PCr depletion to 60% of resting values and with pH values of > 7.0. Then two 1-min protocols of rapid plantar flexion were performed to deplete PCr values to 5-20% of resting values with pH values of < 6.8. Areas of PCr peaks (every 8 s) and HbO2 saturation (every 1 s) were fit to a monoexponential function, and a time constant was calculated. The PCr time constant was larger after maximal exercise (68.3 +/- 10.5 s) than after submaximal exercise (36.0 +/- 6.5 s), which is consistent with the effects of low pH on PCr recovery. HbO2 resaturation approximated submaximal PCr recovery and was not different between maximal (29.4 +/- 5.5 s) and submaximal (27.6 +/- 6.0 s) exercise. We conclude that magnetic resonance spectroscopy measurements of PCr recovery and near-infrared spectroscopy measurements of recovery of HbO2 saturation provide similar information as long as muscle pH remains near 7.0.