High-energy Phosphate Metabolism Research Articles

Cardiac 31P-MRS compared to echocardiographic findings in patients with hypertensive heart disease without overt systolic dysfunction—Preliminary results

Purpose To evaluate changes in high energy phosphate (HEP) metabolism in patients with hypertension and diastolic dysfunction but with normal LVEF > 55% assessed by echocardiography and tissue Doppler. Material and methods 20 patients (16 men and 4 women, mean age 57 ± 13 years) were studied with phosphorus magnetic resonance spectroscopy and echocardiography. MRS was performed at 1.5 T using an ECG-gated CSI sequence with nuclear Overhauser effect. According to echocardiographical findings 12 patients were found to have a diastolic dysfunction, whereas 8 patients were identified as normal, serving as control group in the following statistical analysis. All patients had normal systolic function (LVEF > 55%).Statistical analysis was made by using mean ± S.D. for description of the data, Spearman correlation and two-tailed Student's t-test for independent samples. Results No differences were found in weight, age, LVEF, endsystolic volume, end-diastolic volume, cardiac output and BNP levels between patients and control group. Myocardial mass at end-diastole correlated significantly with PCr/ATP ratio ( r = −0.66; p = 0.04) in patients and control group. Myocardial PCr/ATP ratio in patients was significantly decreased compared to controls (1.21 ± 0.22 vs. 1.54 ± 0.24; p = 0.006). Conclusions Cardiac 31P-MRS might offer a noninvasive means for detecting early states of heart failure in hypertensive patients.

Increased mitochondrial uncoupling proteins, respiratory uncoupling and decreased efficiency in the chronically infarcted rat heart

Heart failure patients have abnormal cardiac high energy phosphate metabolism, the explanation for which is unknown. Patients with heart failure also have elevated plasma free fatty acid (FFA) concentrations. Elevated FFA levels are associated with increased cardiac mitochondrial uncoupling proteins (UCPs), which, in turn, are associated with decreased mitochondrial respiratory coupling and low cardiac efficiency. Here, we determined whether increased mitochondrial UCP levels contribute to decreased energetics in the failing heart by measuring UCPs and respiration in mitochondria isolated from the viable myocardium of chronically infarcted rat hearts and measuring efficiency (hydraulic work/O 2 consumption) in the isolated, working rat heart. Ten weeks after infarction, cardiac levels of UCP3 were increased by 53% in infarcted, failing hearts that had ejection fractions less than 45%. Cardiac UCP3 levels correlated positively with non-fasting plasma FFAs ( r = 0.81; p < 0.01). Mitochondria from failing hearts were less coupled than those from control hearts, as demonstrated by the lower ADP/O ratio of 1.9 ± 0.1 compared with 2.5 ± 0.2 in controls ( p < 0.05). The decreased ADP/O ratio was reflected in an efficiency of 14 ± 2% in the failing hearts when perfused with 1 mM palmitate, compared with 20 ± 1% in controls ( p < 0.05). We conclude that failing hearts have increased UCP3 levels that are associated with high circulating FFA concentrations, mitochondrial uncoupling, and decreased cardiac efficiency. Thus, respiratory uncoupling may underlie the abnormal energetics and low efficiency in the failing heart, although whether this is maladaptive or adaptive would require direct investigation.

Phosphorus-31 Two-Dimensional Chemical Shift Imaging in the Myocardium of Patients with Late Onset of Friedreich Ataxia

Friedreich ataxia (FRDA) is characterized by GAA expansions in the intron 1 of the frataxin gene correlating with disease onset and progression as well as cardiac affection. Accordingly, FRDA patients with early disease onset show a clear impairment of mitochondrial function in the myocardium. The purpose of this study was to investigate cardiac function and high-energy phosphate metabolism in FRDA patients with late disease onset. Using a 1.5 T magnetic resonance scanner, cardiac phosphorus-31 two-dimensional chemical shift imaging was performed in ten patients (seven male, three female) with a late onset of FRDA and in 35 healthy, male controls. Ejection faction (EF) and interventricular septum thickness (IST) were determined by echocardiography. The differences in left ventricular phosphocreatine (PCr) to beta-adenosine triphosphate (beta-ATP) ratios between both groups were not significant. FRDA patients had increased ISTs (10.8+/-1.6 vs. 9.7+/-0.9 mm; p=0.048), which correlated significantly with the left ventricular PCr to beta-ATP ratios (r= -0.644; p=0.04), and decreased EFs (52.24+/-7.72% vs. 64.09+/-4.25%; p=0.001) compared to normal controls. In contrast to FRDA patients with early disease onset, our patients collective exhibited a normal, probably compensated cardiac mitochondrial function, whereby IST and EF were mildly altered.

Acute effect of antidiabetic 1,4‐dihydropyridine compound cerebrocrast on cardiac function and glucose metabolism in the isolated, perfused normal rat heart

Diabetes mellitus (DM) is an important cardiovascular risk factor and is associated with abnormalities in endothelial and vascular smooth muscle cell function, evoked by chronic hyperglycemia and hyperlipidemia. Chronic insulin deficiency or resistance is marked by decreases in the intensity of glucose transport, glucose phosphorylation, and glucose oxidation, plus decreases in ATP levels in cardiac myocytes. It is important to search for new agents that promote glucose consumption in the heart and partially inhibit extensive fatty acid beta-oxidation observed in diabetic, ischemia. When the oxygen supply for myocardium is decreased, the heart accumulates potentially toxic intermediates of fatty acid beta-oxidation, that is, long-chain acylcarnitine and long-chain acyl-CoA metabolites. Exogenous glucose and heart glycogen become an important compensatory source of energy. Therefore we studied the effect of the antidiabetic 1,4-dihydropyridine compound cerebrocrast at concentrations from 10(-10) M to 10(-7) M on isolated rat hearts using the method of Langendorff, on physiological parameters and energy metabolism. Cerebrocrast at concentrations from 10(-10) M to 10(-7) M has a negative inotropic effect on the rat heart. It inhibits L-type Ca(2+)channels thereby diminishing the cellular Ca(2+) supply, reducing contractile activity, and oxygen consumption, that normally favors enhanced glucose uptake, metabolism, and production of high-energy phosphates (ATP content) in myocardium. Cerebrocrast decreases heart rate and left ventricular (LV) systolic pressure; at concentrations of 10(-10) M and 10(-9) M it evokes short-term vasodilatation of coronary arteries. Increase of ATP content in the myocytes induced by cerebrocrast has a ubiquitous role. It can preserve the integrity of the cell plasma membranes, maintain normal cellular function, and inhibit release of lactate dehydrogenase (LDH) from cells that is associated with diabetes and heart ischemia. Administration of cerebrocrast together with insulin shows that both compounds only slightly enhance glucose uptake in myocardium, but significantly normalize the rate of contraction and relaxation ( +/- dp/dt). The effect of insulin on coronary flow is more pronounced by administration of insulin together with cerebrocrast at a concentration of 10(-7) M. Cerebrocrast may promote a shift of glucose consumption from aerobic to anerobic conditions (through the negative inotropic properties), and may be very significant in prevention of cardiac ischemic episodes.

Creatine monohydrate in resistant depression: a preliminary study

Creatine plays a pivotal role in brain energy homeostasis, and altered cerebral energy metabolism may be involved in the pathophysiology of depression. Oral creatine supplementation may modify brain high-energy phosphate metabolism in depressed subjects. Eight unipolar and two bipolar patients with treatment-resistant depression were treated for four weeks with 3-5 g/day of creatine monohydrate in an open add-on design. Outcome measures were the Hamilton Depression Rating Scale, Hamilton Anxiety Scale, and Clinical Global Impression scores, recorded at baseline and at weeks 1, 2, 3 and 4. One patient improved considerably after one week and withdrew. Both bipolar patients developed hypomania/mania. For the remaining seven patients, all scale scores significantly improved. Adverse reactions were mild and transitory. This small, preliminary, open study of creatine monohydrate suggests a beneficial effect of creatine augmentation in unipolar depression, but possible precipitation of a manic switch in bipolar depression.

Differential energetic response of brain vs. skeletal muscle upon glycemic variations in healthy humans

The brain regulates all metabolic processes within the organism, and therefore, its energy supply is preserved even during fasting. However, the underlying mechanism is unknown. Here, it is shown, using (31)P-magnetic resonance spectroscopy that during short periods of hypoglycemia and hyperglycemia, the brain can rapidly increase its high-energy phosphate content, whereas there is no change in skeletal muscle. We investigated the key metabolites of high-energy phosphate metabolism as rapidly available energy stores by (31)P MRS in brain and skeletal muscle of 17 healthy men. Measurements were performed at baseline and during dextrose or insulin-induced hyperglycemia and hypoglycemia. During hyperglycemia, phosphocreatine (PCr) concentrations increased significantly in the brain (P = 0.013), while there was a similar trend in the hypopglycemic condition (P = 0.055). Skeletal muscle content remained constant in both conditions (P > 0.1). ANOVA analyses comparing changes from baseline to the respective glycemic plateau in brain (up to +15%) vs. muscle (up to -4%) revealed clear divergent effects in both conditions (P < 0.05). These effects were reflected by PCr/Pi ratio (P < 0.05). Total ATP concentrations revealed the observed divergency only during hyperglycemia (P = 0.018). These data suggest that the brain, in contrast to peripheral organs, can activate some specific mechanisms to modulate its energy status during variations in glucose supply. A disturbance of these mechanisms may have far-reaching implications for metabolic dysregulation associated with obesity or diabetes mellitus.

A Conserved Role for Phosphatidylinositol 3-Kinase but Not Akt Signaling in Mitochondrial Adaptations that Accompany Physiological Cardiac Hypertrophy

Physiological cardiac hypertrophy is associated with mitochondrial adaptations that are characterized by activation of PGC-1alpha and increased fatty acid oxidative (FAO) capacity. It is widely accepted that phosphatidylinositol 3-kinase (PI3K) signaling to Akt1 is required for physiological cardiac growth. However, the signaling pathways that coordinate physiological hypertrophy and metabolic remodeling are incompletely understood. We show here that activation of PI3K is sufficient to increase myocardial FAO capacity and that inhibition of PI3K signaling prevents mitochondrial adaptations in response to physiological hypertrophic stimuli despite increased expression of PGC-1alpha. We also show that activation of the downstream kinase Akt is not required for the mitochondrial adaptations that are secondary to PI3K activation. Thus, in physiological cardiac growth, PI3K is an integrator of cellular growth and metabolic remodeling. Although PI3K signaling to Akt1 is required for cellular growth, Akt-independent pathways mediate the accompanying mitochondrial adaptations.

Effect of the sporting discipline on the right and left ventricular morphology and function of elite male track runners: A magnetic resonance imaging and phosphorus 31 spectroscopy study

Professional, long-term physical training is often associated with morphological and metabolic changes in the heart. This study was undertaken to assess the left ventricular (LV) and right ventricular (RV) morphology and function and the LV high-energy phosphates of athletes trained to a sustained power or aerobic exercise. Magnetic resonance imaging (MRI) of the LV and RV and phosphorous 31 magnetic resonance spectroscopy of the LV were performed by means of a 1.5-T clinical scanner in 23 elite track sprinters (sustained power or anaerobic power sprint training, 100-400 m) or marathon runners (sustained aerobic endurance training) and in 10 sedentary, young, lean men. Athletes had LV hypertrophy and unaffected chamber size, systolic and diastolic functions, and high-energy phosphates metabolism. Also, the RV of the athletes was hypertrophied in comparison with that of the nonathletic controls, and the systolic and diastolic functions were unaffected; the chamber volume was higher in the sprinters (end-diastolic volume 190 +/- 15 mL) in comparison with that of the marathon runners (174 +/- 19 mL, P < .05) and controls (168 +/- 19 mL, P < .01) even if this difference, when adjusted for body surface area, was maintained only when compared with that of controls (P < .02). Left ventricular and RV hypertrophy in athletes is associated with normal systolic and diastolic functions and resting cardiac energy metabolism, supporting its benign nature. A more pronounced RV dilatation was found in the anaerobic power athletes and further investigation is warranted to establish the clinical significance of this training effect.

Short-Term Caloric Restriction Induces Accumulation of Myocardial Triglycerides and Decreases Left Ventricular Diastolic Function in Healthy Subjects

Diabetes and obesity are associated with increased plasma nonesterified fatty acid (NEFA) levels, myocardial triglyceride accumulation, and myocardial dysfunction. Because a very low-calorie diet (VLCD) also increases plasma NEFA levels, we studied the effect of a VLCD on myocardial triglyceride content and cardiac function in healthy subjects. Fourteen healthy nonobese men underwent (1)H-magnetic resonance spectroscopy (MRS) to determine myocardial and hepatic triglyceride content, (31)P-MRS to assess myocardial high-energy phosphate (HEP) metabolism (phosphocreatine/ATP), and magnetic resonance imaging of myocardial function at baseline and after a 3-day VLCD. After the dietary intervention, plasma NEFA levels increased compared with those at baseline (from 0.5 +/- 0.1 to 1.1 +/- 0.1 mmol/l, P < 0.05). Concomitantly, myocardial triglyceride content increased by approximately 55% compared with that at baseline (from 0.38 +/- 0.05 to 0.59 +/- 0.06%, P < 0.05), whereas liver triglyceride content decreased by approximately 32% (from 2.2 +/- 0.5 to 1.5 +/- 0.4%, P < 0.05). The VLCD did not change myocardial phosphocreatine-to-ATP ratio (2.33 +/- 0.15 vs. 2.33 +/- 0.08, P > 0.05) or systolic function. Interestingly, deceleration of the early diastolic flow across the mitral valve decreased after the VLCD (from 3.37 +/- 0.20 to 2.91 +/- 0.16 ml/s(2) x 10(-3), P < 0.05). This decrease in diastolic function was significantly correlated with the increase in myocardial triglyceride content. Short-term VLCD induces accumulation of myocardial triglycerides. In addition, VLCD decreases left ventricular diastolic function, without alterations in myocardial HEP metabolism. This study documents diet-dependent physiological variations in myocardial triglyceride content and diastolic function in healthy subjects.

Impact of Exercise Capacity on Myocardial High-Energy Phosphate Metabolism

31-Phosphorous magnetic resonance spectroscopy (31P MRS) is a unique tool to investigate IN VIVO high-energy phosphates (HEP) in the human heart. We hypothesized that physical capacity may be associated with myocardial HEP status. Healthy, male volunteers (n = 105, mean age 51 +/- 7 years) underwent bicycle ergometry with a stepwise increasing workload to determine maximal working capacity (MWC). Heart rate (HR) and blood pressure (BP) were measured continuously during exercise and 4 minutes of recovery. Further 31-Phosphorous 2-dimensional chemical shift imaging (31P 2D CSI) MRS was performed to assess myocardial HEP metabolism by determining phosphocreatinine to beta-ATP ratios (PCr/b-ATP) using a 1.5 tesla scanner. Volunteers with MWC > 230 Watt had significantly higher PCr/b-ATP ratios than those with MWC < 200 Watt (1.93 +/- 0.36 vs. 1.59 +/- 0.35; p < 0.001). Additionally, those with a recovery systolic (S)BP < 195 mmHg had significantly higher ratios than those with a recovery SBP > 195 mmHg (1.74 +/- 0.3 vs. 1.51 +/- 0.2; p < 0.05). We observed a linear correlation between the PCr/b-ATP ratio and MWC (r = 0.411; p < 0.001) and recovery SBP (r = - 0.290; p < 0.01). After statistical correction for age, these correlations remained significant. In this study, we observed a correlation of parameters of physical fitness determined by bicycle exercise testing and cardiac PCr/b-ATP ratios.

Altered Kidney Graft High-Energy Phosphate Metabolism in Kidney-Transplanted End-Stage Renal Disease Type 1 Diabetic Patients

Diabetes, hypertension, dyslipidemia, obesity, nephrotoxicity of certain immunosuppressive drugs, and the persistence of a chronic alloimmune response may significantly affect graft survival in end-stage renal disease (ESRD) type 1 diabetic patients who have undergone kidney transplant. The aim of this study was to ascertain the impact of kidney alone (KD) or combined kidney-pancreas (KP) transplantation on renal energy metabolism. We assessed high-energy phosphates (HEPs) metabolism by using, in a cross-sectional fashion, 31P-magnetic resonance spectroscopy in the graft of ESRD type 1 diabetic transplanted patients who received KD (n = 20) or KP (n = 20) transplant long before the appearance of overt chronic allograft nephropathy (CAN). Ten nondiabetic microalbuminuric kidney transplanted patients and 10 nondiabetic kidney transplanted patients with overt CAN were chosen as controls subjects. Simultaneous KP transplantation patients showed a higher beta-ATP/inorganic phosphorus (Pi) ratio (marker of the graft energy status) versus the other groups, and a positive correlation between beta-ATP/Pi phosphorus ratio and A1C was found. In the analysis limited to the subgroup of normoalbuminuric patients, the difference in beta-ATP/Pi was still detectable in KP patients compared with KD transplantation. KP transplantation was associated with better HEPs than in KD transplantation, suggesting that restoration of beta-cell function positively affects kidney graft metabolism.

Magnetic resonance tomography and spectroscopy investigations of the human heart

The use of cardiac magnetic resonance (CMR) has emerged in the last decades. Technical innovations provide fast and high-quality imaging sequences and CMR is often proposed as a gold-standard for the in vivo evaluation of cardiac function, morphologic details and infarct size. Also the 31-phosphorous magnetic resonance spectroscopy (MRS) is a unique tool to investigate the human myocardial high-energy phosphate (HEP) metabolism in vivo. PCr/b-ATP ratio examined by MRS is mainly used as an index for cardiac energy metabolism. We have described decreased PCr/b-ATP ratios in patients with diabetes mellitus, hypercholesterolemia and hemochromatosis. The use of CMR to study the effects of ischemia time on the evolution of myocardial infarct characteristics after an acute myocardial infarction (AMI) treated with a primary angioplasty (p-PTCA) is a promising new application of this technique. Results of this study will further help to clarify the impact of ischemia time on myocardial regional functional recovery after p-PTCA.

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.

Abstract 4191: Abnormal Cardiac Energetics are Associated with Diastolic Dysfunction in Uncomplicated Obesity

Background: Abnormal cardiac high energy phosphate metabolism may lead to contractile dysfunction in heart failure. As the incidence of heart failure is increased in obesity, we have determined whether cardiac energy metabolism is abnormal in healthy, obese subjects. Methods and Results: Cardiac phosphocreatine (PCr) to ATP ratios and function were measured using magnetic resonance spectroscopy and imaging, respectively, in 20 asymptomatic obese adults and 19 age- and sex-matched controls. Fasting plasma leptin, glucose, insulin, C-reactive protein, lipid and free fatty acid (FFA) concentrations were also measured. With a mean body mass index (BMI) of 31 kg/m2, the obese subjects had 16% lower cardiac PCr/ATP ratios and 54% higher fasting plasma FFA concentrations than the control subjects, who had a mean BMI of 24 kg/m2. Multivariate stepwise linear regression analysis demonstrated that plasma FFA concentrations (β −0.5, P = 0.001) and BMI (β −0.3, P = 0.03) were significant independent predictors of the cardiac PCr/ATP ratio (model adjusted R2 = 0.46). The peak filling rate, a measure of diastolic dysfunction, correlated with the cardiac PCr/ATP ratio (r = 0.42, P = 0.013). Conclusions: Uncomplicated obesity is associated with decreased cardiac PCr/ATP ratios, diastolic dysfunction and increased plasma FFA concentrations, raising the possibility that abnormal cardiac high energy phosphate metabolism may contribute to the increased incidence of heart failure in obesity.

Altered high-energy phosphate metabolism predicts contractile dysfunction and subsequent ventricular remodeling in pressure-overload hypertrophy mice.

To study the role of early energetic abnormalities in the subsequent development of heart failure, we performed serial in vivo combined magnetic resonance imaging (MRI) and (31)P magnetic resonance spectroscopy (MRS) studies in mice that underwent pressure-overload following transverse aorta constriction (TAC). After 3 wk of TAC, a significant increase in left ventricular (LV) mass (74 +/- 4 vs. 140 +/- 26 mg, control vs. TAC, respectively; P < 0.000005), size [end-diastolic volume (EDV): 48 +/- 3 vs. 61 +/- 8 microl; P < 0.005], and contractile dysfunction [ejection fraction (EF): 62 +/- 4 vs. 38 +/- 10%; P < 0.000005] was observed, as well as depressed cardiac energetics (PCr/ATP: 2.0 +/- 0.1 vs. 1.3 +/- 0.4, P < 0.0005) measured by combined MRI/MRS. After an additional 3 wk, LV mass (140 +/- 26 vs. 167 +/- 36 mg; P < 0.01) and cavity size (EDV: 61 +/- 8 vs. 76 +/- 8 microl; P < 0.001) increased further, but there was no additional decline in PCr/ATP or EF. Cardiac PCr/ATP correlated inversely with end-systolic volume and directly with EF at 6 wk but not at 3 wk, suggesting a role of sustained energetic abnormalities in evolving chamber dysfunction and remodeling. Indeed, reduced cardiac PCr/ATP observed at 3 wk strongly correlated with changes in EDV that developed over the ensuing 3 wk. These data suggest that abnormal energetics due to pressure overload predict subsequent LV remodeling and dysfunction.

Abnormal Cardiac High-Energy Phosphate Metabolism in a Patient With Type 2 Diabetes Mellitus

Abnormal Cardiac High-Energy Phosphate Metabolism in a Patient With Type 2 Diabetes Mellitus

PPARα is involved in triiodothyronine-induced cardiac hypertrophy and high-energy phosphate metabolism: A 31P MRS study of the PPARα-null mouse

Triiodothyronine (T3) acts via nuclear receptors to cause cardiac hypertrophy and alter cardiac energy metabolism. Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor that plays an important role in cardiac fatty acid metabolism. Both the T3 receptor and PPARα form heterodimers with the retinoid × receptor (RXR), the heterodimers bind to T3 and peroxisome proliferator response elements, respectively, to stimulate the transcription of T3-responsive genes or genes involved in fatty acid metabolism.

Open Study of Creatine Monohydrate in Treatment-Resistant Posttraumatic Stress Disorder

Article AbstractBecause this piece does not have an abstract, we have provided for your benefit the first 3 sentences of the full text.Sir: Creatine-containing compounds play an important role in brain energy homeostasis and may have a beneficial effect on brain functioning.1-3 Accumulated evidence suggests the possible involvement of altered cerebral energy metabolism in the pathophysiology of posttraumatic stress disorder (PTSD).4 Oral creatine supplementation may increase brain creatine level and modify brain high-energy phosphate metabolism in hypoactive brain areas in subjects with treatment-resistant PTSD.†‹

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.