Post-exercise Phosphocreatine Research Articles

Post-exercise intramuscular O2 supply is tightly coupled with a higher proximal-to-distal ATP synthesis rate in human tibialis anterior.

Key points The post‐exercise recovery of phosphocreatine, a measure of the oxidative capacity of muscles, as assessed by 31P MR spectroscopy, shows a striking increase from distal to proximal along the human tibialis anterior muscle.To investigate why this muscle exhibits a greater oxidative capacity proximally, we tested whether the spatial variation in phosphocreatine recovery rate is related to oxygen supply, muscle fibre type or type of exercise.We revealed that oxygen supply also increases from distal to proximal along the tibialis anterior, and that it strongly correlated with phosphocreatine recovery. Carnosine level, a surrogate measure for muscle fibre type was not different between proximal and distal, and type of exercise did not affect the gradient in phosphocreatine recovery rate.Taken together, the findings of this study suggest that the post‐exercise spatial gradients in oxygen supply and phosphocreatine recovery are driven by a higher intrinsic mitochondrial oxidative capacity proximally. Phosphorus magnetic resonance spectroscopy (31P MRS) of human tibialis anterior (TA) revealed a strong proximo‐distal gradient in the post‐exercise phosphocreatine (PCr) recovery rate constant (k PCr), a measure of muscle oxidative capacity. The aim of this study was to investigate whether this k PCr gradient is related to O2 supply, resting phosphorylation potential, muscle fibre type, or type of exercise. Fifteen male volunteers performed continuous isometric ankle dorsiflexion at 30% maximum force until exhaustion. At multiple locations along the TA, we measured the oxidative PCr resynthesis rate (V PCr = k PCr × PCr depletion) by 31P MRS, the oxyhaemoglobin recovery rate constant (k O2Hb) by near infrared spectroscopy, and muscle perfusion with MR intravoxel incoherent motion imaging. The k O2Hb, k PCr, V PCr and muscle perfusion depended on measurement location (P < 0.001, P < 0.001, P = 0.032 and P = 0.003, respectively), all being greater proximally. The k O2Hb and muscle perfusion correlated with k PCr (r = 0.956 and r = 0.852, respectively) and V PCr (r = 0.932 and r = 0.985, respectively), the latter reflecting metabolic O2 consumption. Resting phosphorylation potential (PCr/inorganic phosphate) was also higher proximally (P < 0.001). The surrogate for fibre type, carnosine content measured by 1H MRS, did not differ between distal and proximal TA (P = 0.884). Performing intermittent exercise to avoid exercise ischaemia, still led to larger k PCr proximally than distally (P = 0.013). In conclusion, the spatial k PCr gradient is strongly associated with the spatial variation in O2 supply. It cannot be explained by exercise‐induced ischaemia nor by fibre type. Our findings suggest it is driven by a higher proximal intrinsic mitochondrial oxidative capacity, apparently to support contractile performance of the TA.

Effect of allopurinol on phosphocreatine recovery and muscle function in older people with impaired physical function: a randomised controlled trial.

BackgroundAllopurinol has vascular antioxidant effects and participates in purinergic signalling within muscle. We tested whether allopurinol could improve skeletal muscle energetics and physical function in older people with impaired physical performance.MethodsWe conducted a randomised, double blind, parallel group, placebo-controlled trial, comparing 20 weeks of allopurinol 600 mg once daily versus placebo. We recruited community-dwelling participants aged 65 and over with baseline 6-min walk distance of <400 m and no contraindications to magnetic resonance imaging scanning. Outcomes were measured at baseline and 20 weeks. The primary outcome was post-exercise phosphocreatine (PCr) recovery rate measured using 31P magnetic resonance spectroscopy of the calf. Secondary outcomes included 6-min walk distance, short physical performance battery (SPPB), lean body mass measured by bioimpedance, endothelial function and quality of life.ResultsIn total, 124 participants were randomised, mean age 80 (SD 6) years. A total of 59 (48%) were female, baseline 6-min walk distance was 293 m (SD 80 m) and baseline SPPB was 8.5 (SD 2.0). Allopurinol did not significantly improve PCr recovery rate (treatment effect 0.10 units [95% CI, −0.07 to 0.27], P = 0.25). No significant changes were seen in endothelial function, quality of life, lean body mass or SPPB. Allopurinol improved 6-min walk distance (treatment effect 25 m [95% 4–46, P = 0.02]). This was more pronounced in those with high baseline oxidative stress and urate.ConclusionAllopurinol improved 6-min walk distance but not PCr recovery rate in older people with impaired physical function. Antioxidant strategies to improve muscle function for older people may need to be targeted at subgroups with high baseline oxidative stress.

Proteomic signatures of in vivo muscle oxidative capacity in healthy adults.

Adequate support of energy for biological activities and during fluctuation of energetic demand is crucial for healthy aging; however, mechanisms for energy decline as well as compensatory mechanisms that counteract such decline remain unclear. We conducted a discovery proteomic study of skeletal muscle in 57 healthy adults (22 women and 35 men; aged 23–87 years) to identify proteins overrepresented and underrepresented with better muscle oxidative capacity, a robust measure of in vivo mitochondrial function, independent of age, sex, and physical activity. Muscle oxidative capacity was assessed by 31P magnetic resonance spectroscopy postexercise phosphocreatine (PCr) recovery time (τPCr) in the vastus lateralis muscle, with smaller τPCr values reflecting better oxidative capacity. Of the 4,300 proteins quantified by LC‐MS in muscle biopsies, 253 were significantly overrepresented with better muscle oxidative capacity. Enrichment analysis revealed three major protein clusters: (a) proteins involved in key energetic mitochondrial functions especially complex I of the electron transport chain, tricarboxylic acid (TCA) cycle, fatty acid oxidation, and mitochondrial ABC transporters; (b) spliceosome proteins that regulate mRNA alternative splicing machinery, and (c) proteins involved in translation within mitochondria. Our findings suggest that alternative splicing and mechanisms that modulate mitochondrial protein synthesis are central features of the molecular mechanisms aimed at maintaining mitochondrial function in the face of impairment. Whether these mechanisms are compensatory attempt to counteract the effect of aging on mitochondrial function should be further tested in longitudinal studies.

Aerobic-Strength Exercise Improves Metabolism and Clinical State in Parkinson's Disease Patients.

www.ClinicalTrials.gov, identifier NCT02253732.

Ectopic lipid storage in non-alcoholic fatty liver disease is not mediated by impaired mitochondrial oxidative capacity in skeletal muscle.

Non-alcoholic fatty liver disease (NAFLD), characterized by lipid deposition within the liver [intrahepatocellular lipid (IHCL)], is associated with insulin resistance and the metabolic syndrome (MS). It has been suggested that impaired skeletal muscle mitochondrial function may contribute to ectopic lipid deposition, and the associated MS, by altering post-prandial energy storage. To test this hypothesis, we performed a cross-sectional study of 17 patients with NAFLD [mean±S.D.; age, 45±11years; body mass index (BMI), 31.6±3.4kg/m2] and 18 age- and BMI-matched healthy controls (age, 44±11years; BMI, 30.5±5.2kg/m2). We determined body composition by MRI, IHCL and intramyocellular (soleus and tibialis anterior) lipids (IMCLs) by proton magnetic resonance spectroscopy (1H-MRS) and skeletal muscle mitochondrial function by dynamic phosphorus magnetic resonance spectroscopy (31P-MRS) of quadriceps muscle. Although matched for BMI and total adiposity, after statistical adjustment for gender, patients with NAFLD (defined by IHCL ≥ 5.5%) had higher IHCLs (25±16% compared with 2±2%; P<0.0005) and a higher prevalence of the MS (76% compared with 28%) compared with healthy controls. Despite this, the visceral fat/subcutaneous fat ratio, IMCLs and muscle mitochondrial function were similar between the NAFLD and control groups, with no significant difference in the rate constants of post-exercise phosphocreatine (PCr) recovery (1.55±0.4 compared with 1.51±0.4 min-1), a measure of muscle mitochondrial function. In conclusion, impaired muscle mitochondrial function does not seem to underlie ectopic lipid deposition, or the accompanying features of the MS, in patients with NAFLD.

Insulin Resistance and Impaired Mitochondrial Function in Obese Adolescent Girls

Mitochondrial dysfunction plays a role in the development of muscle insulin resistance (IR) and the accumulation of intramyocellular lipid (IMCL) in skeletal muscle that can, in turn, interfere with insulin signaling. The purpose of this study was to assess mitochondrial function (MF) and IMCL in obese adolescent girls with and without IR to determine whether: (1) Girls with IR have impaired MF, and (2) impaired MF in girls with IR is related to higher IMCL. We examined 22 obese girls aged 13-21 years old for IR [defined as a homeostasis model assessment of insulin resistance (HOMA-IR) value >4. Phosphorus magnetic resonance spectroscopy (31P-MRS) and proton magnetic resonance spectroscopy (1H-MRS), respectively, were used to determine MF and IMCL of the soleus muscle along with magnetic resonance imaging (MRI) measures of visceral, subcutaneous, and total adipose tissue (VAT, SAT, and TAT) in girls with HOMA-IR >4 (insulin-resistant group) versus HOMA-IR ≤ 4 (insulin-sensitive group). Serum lipids and waist-to-hip ratio (W/H) were also measured. Girls with IR (n=8) did not differ from the insulin-sensitive group (n=14) for age, bone age, weight, VAT, SAT, TAT, or IMCL. However, the insulin-resistant group had higher W/H. Additionally the insulin-resistance group had a lower log rate of postexercise phosphocreatine (PCr) recovery (ViPCr) and a higher log PCr recovery constant (tau), indicative of impaired MF. Obese girls with increased IR have impaired mitochondrial function. This association is not mediated by alterations in IMCL or adipose tissue. Further studies are necessary to determine whether there is a causal relation between impaired mitochondrial function and IR in obesity and mediators of such a relationship.

AB1170 Clinical whole-body exercise testing in a magnetic resonance scanner: A feasibility study in children with chronic inflammatory myopathy

BackgroundExercise is increasingly utilized as a non-pharmacological intervention in the clinical management of patients with chronic inflammatory conditions. Availability of more objective microscopic outcome measures that provide functional information at...

Postexercise phosphocreatine recovery, an index of mitochondrial oxidative phosphorylation, is reduced in diabetic patients with lower extremity complications

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.

Altering the rest interval during high‐intensity interval training does not affect muscle or performance adaptations

It has been hypothesized that exercise-induced changes in metabolites and ions are crucial in the adaptation of contracting muscle. We tested this hypothesis by comparing adaptations to two different interval-training protocols (differing only in the rest duration between intervals), which provoked different perturbations in muscle metabolites and acid-base status. Prior to and immediately after training, 12 women performed the following tests: (1) a graded exercise test to determine peak oxygen uptake (V(O2)); (2) a high-intensity exercise bout (followed 60 s later by a repeated-sprint-ability test; and (3) a repeat of the high-intensity exercise bout alone with muscle biopsies pre-exercise, immediately postexercise and after 60 s of recovery. Subjects performed 5 weeks (3 days per week) of training, with either a short (1 min; HIT-1) or a long rest period (3 min; HIT-3) between intervals; training intensity and volume were matched. Muscle [H(+)] (155 ± 15 versus 125 ± 8 nmol l(-1); P < 0.05) and muscle lactate content (84.2 ± 7.9 versus 46.9 ± 3.1 mmol (g wet weight)(-1)) were both higher after HIT-1, while muscle phosphocreatine (PCr) content (52.8 ± 8.3 versus 63.4 ± 9.8 mmol (g wet weight)(-1)) was lower. There were no significant differences between the two groups regarding the increases in , repeated-sprint performance or muscle Na(+),K(+)-ATPase content. Following training, both groups had a significant decrease in postexercise muscle [H(+)] and lactate content, but not postexercise ATP or PCr. Postexercise PCr resynthesis increased following both training methods. In conclusion, intense interval training results in marked improvements in muscle Na(+),K(+)-ATPase content, PCr resynthesis and . However, manipulation of the rest period during intense interval training did not affect these changes.

The Feasibility of Measuring Phosphocreatine Recovery Kinetics in Muscle Using a Single-shot 31P RARE MRI Sequence

Heterogeneity of skeletal muscle structure, composition, and perfusion results in spatial differences in oxidative function between muscles and muscle regions. The simultaneous measurement of the postexercise phosphocreatine (PCr) recovery rate across all muscles of a human limb cross-section may provide new insights into normal physiology and disease states. The objective of this work was to assess the feasibility of acquiring PCr rapid acquisition with relaxation enhancement (RARE) images with sufficient temporal and spatial resolution to accurately measure PCr recovery kinetics in a cross-section of a human limb. One normal subject performed a finger exercise until fatigued. At cessation of exercise surface coil localized pulse-and-acquire phosphorus-31 MR spectra ((31)P- magnetic resonance spectroscopy [MRS]) of the forearm were acquired at 6 S intervals for 4 minutes. The exercise protocol was repeated 7 days later and axial PCr RARE images of the forearm were acquired following exercise with 5.6 cm(3) voxels at 6-second intervals for 4 minutes. The PCr recovery time constants for the PCr RARE and (31)P-MRS measurements were 91.0 and 91.1 seconds, respectively, based on a monoexponential fit. A Pearson correlation test showed that the PCr recovery data that resulted from the RARE PCr imaging were highly correlated with the data resulting from the (31)P-MRS (r = 0.91, P < .0001). Data from selected regions of RARE PCr images acquired at 6-second intervals compare well to those acquired using surface coil (31)P MR spectroscopy and can provide an accurate assessment of PCr recovery kinetics.

Skeletal muscle metabolic recovery following submaximal exercise in chronic heart failure is limited more by O2 delivery than O2 utilization

CHF (chronic heart failure) is associated with a prolonged recovery of skeletal muscle energy stores following submaximal exercise, limiting the ability to perform repetitive daily activities.However, the pathophysiological background of this impairment is not well established. The aim of the present study was to investigate whether muscle metabolic recovery following submaximal exercise in patients with CHF is limited by O2 delivery or O2 utilization. A total of 13 stable CHF patients (New York Heart Association classes II-III) and eight healthy subjects, matched for age and BMI (body mass index), were included. All subjects performed repetitive submaximal dynamic single leg extensions in the supine position. Post-exercise PCr (phosphocreatine) resynthesis was assessed by 31P-MRS (magnetic resonance spectroscopy). NIRS (near-IR spectroscopy) was applied simultaneously, using the rate of decrease in HHb (deoxygenated haemoglobin) as an index of post-exercise muscle re-oxygenation. As expected, PCr recovery was slower in CHF patients than in control subjects (time constant, 47+/-10 compared with 35+/-12 s respectively; P=0.04). HHb recovery kinetics were also prolonged in CHF patients (mean response time, 74+/-41 compared with 44+/-17 s respectively; P=0.04). In the patient group, HHb recovery kinetics were slower than PCr recovery kinetics (P=0.02), whereas no difference existed in the control group(P=0.32). In conclusion, prolonged metabolic recovery in CHF patients is associated with an even slower muscle tissue re-oxygenation, indicating a lower O(2) delivery relative to metabolic demands. Therefore we postulate that the impaired ability to perform repetitive daily activities in these patients depends more on a reduced muscle blood flow than on limitations in O(2) utilization.

Reply to Kemp

to the editor: In his letter ([8][1]), Dr. Kemp refers to a model of ATP synthesis control in which the mechanisms during the rest-to-work transient (on-transient) and the work-to-rest transient (off-transient) are the same. Accordingly, only one mathematical representation is used for both

Early or advanced stage type 2 diabetes is not accompanied by in vivo skeletal muscle mitochondrial dysfunction

Several lines of evidence support a potential role of skeletal muscle mitochondrial dysfunction in the pathogenesis of insulin resistance and/or type 2 diabetes. However, it remains to be established whether mitochondrial dysfunction represents either cause or consequence of the disease. We examined in vivo skeletal muscle mitochondrial function in early and advanced stages of type 2 diabetes, with the aim to gain insight in the proposed role of mitochondrial dysfunction in the aetiology of insulin resistance and/or type 2 diabetes. Ten long-standing, insulin-treated type 2 diabetes patients, 11 subjects with impaired fasting glucose, impaired glucose tolerance and/or recently diagnosed type 2 diabetes, and 12 healthy, normoglycaemic controls, matched for age and body composition and with low habitual physical activity levels were studied. In vivo mitochondrial function of the vastus lateralis muscle was evaluated from post-exercise phosphocreatine (PCr) recovery kinetics using (31)P magnetic resonance spectroscopy (MRS). Intramyocellular lipid (IMCL) content was assessed in the same muscle using single-voxel (1)H MRS. IMCL content tended to be higher in the type 2 diabetes patients when compared with normoglycaemic controls (P=0.06). The(31)P MRS parameters for mitochondrial function, i.e. PCr and ADP recovery time constants and maximum aerobic capacity, did not differ between groups. The finding that in vivo skeletal muscle oxidative capacity does not differ between long-standing, insulin-treated type 2 diabetes patients, subjects with early stage type 2 diabetes and sedentary, normoglycaemic controls suggests that mitochondrial dysfunction does not necessarily represent either cause or consequence of insulin resistance and/or type 2 diabetes.

Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo‐controlled, double‐blind 31P‐MRS crossover study

The purpose of our randomized, double-blind, placebo-controlled crossover study in 15 patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) because of single large-scale mitochondrial (mt) DNA deletions was to determine whether oral creatine (Cr) monohydrate can improve skeletal muscle energy metabolism in vivo. Each treatment phase with Cr in a dosage of 150 mg/kg body weight/day or placebo lasted 6 weeks. The effect of Cr was estimated by phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS), clinical and laboratory tests. (31)P-MRS analysis prior to treatment showed clear evidence of severe mitochondrial dysfunction. However, there were no relevant changes in (31)P-MRS parameters under Cr. In particular, phosphocreatine (PCr)/ATP at rest did not increase, and there was no facilitation of post-exercise PCr recovery. Clinical scores and laboratory tests did not alter significantly under Cr, which was tolerated without major side-effects in all patients. Cr supplementation did not improve skeletal muscle oxidative phosphorylation in our series of patients. However, one explanation for our negative findings may be the short study duration or the limited number of patients included.

Abnormal mitochondrial function and muscle wasting, but normal contractile efficiency, in haemodialysed patients studied non-invasively in vivo.

Muscle dysfunction, which contributes to morbidity in patients on haemodialysis, has several manifestations and a number of possible causes. We applied the non-invasive techniques of (31)P-magnetic resonance spectroscopy ((31)P-MRS), magnetic resonance imaging (MRI) and near-infrared spectroscopy (NIRS) to calf muscle of dialysed patients to define the abnormalities in muscle cross-sectional area (CSA), contractile efficiency, mitochondrial function and vascular O(2) supply. We performed (31)P-MRS/NIRS/MRI studies on the lateral gastrocnemius during isometric plantarflexion and recovery in 23 male patients on haemodialysis (age 24-71 years; haemoglobin 9.9-14.2 g/dl; bicarbonate 17-30 mmol/l; urea reduction ratio 53-77%; parathyroid hormone 1-95 U/l) and 15 male controls (age 29-71 years). To understand the relationships between calf CSA and body mass we also performed MRI only in a further six male patients and 18 male controls. In patients, exercise duration was 30+/-11% lower than in controls. Muscle CSA was lower by 26+/-5%, but contractile efficiency (force/CSA/ATP turnover) was normal. Slowing of post-exercise phosphocreatine (PCr) recovery implied a 22+/-5% defect in effective 'mitochondrial capacity'. That PCr recovery was slow relative to NIRS recovery suggests that this is largely an intrinsic mitochondrial problem (not the result of impaired O(2) supply), one which, furthermore, correlated with CSA. Urea reduction ratio showed a negative correlation with body mass and CSA, but none with PCr rate constant. The relationships to urea reduction ratio reflect the effect of muscle mass on dialysis efficiency, rather than direct effects on muscle CSA or metabolism. The relationship between PCr recovery and calf CSA suggests a role for the mitochondrial defect, whatever its cause, in the development of muscle wasting, although a common cause (e.g. physical inactivity) for both abnormalities cannot be ruled out.

Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo

Phosphocreatine (PCr) resynthesis rate following intense anoxic contraction can be used as a sensitive index of in vivo mitochondrial function. We examined the effect of a diet-induced increase in uncoupling protein 3 (UCP3) expression on postexercise PCr resynthesis in skeletal muscle. Nine healthy male volunteers undertook 20 one-legged maximal voluntary contractions with limb blood flow occluded to deplete muscle PCr stores. Exercise was performed following 7 days consumption of low-fat (LF) or high-fat (HF) diets. Immediately following exercise, blood flow was reinstated, and muscle was sampled after 20, 60, and 120 seconds of recovery. Mitochondrial coupling was assessed by determining the rate of PCr resynthesis during recovery. The HF diet increased UCP3 protein content by approximately 44% compared with the LF diet. However, this HF diet–induced increase in UCP3 expression was not associated with any changes in the rate of muscle PCr resynthesis during conditions of maximal flux through oxidative phosphorylation. Muscle acetylcarnitine, free-creatine, and lactate concentrations during recovery were unaffected by the HF diet. Taken together, our findings demonstrate that increasing muscle UCP3 expression does not diminish the rate of PCr resynthesis, allowing us to conclude that the primary role of UCP3 in humans is not uncoupling.

Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo.

Phosphocreatine (PCr) resynthesis rate following intense anoxic contraction can be used as a sensitive index of in vivo mitochondrial function. We examined the effect of a diet-induced increase in uncoupling protein 3 (UCP3) expression on postexercise PCr resynthesis in skeletal muscle. Nine healthy male volunteers undertook 20 one-legged maximal voluntary contractions with limb blood flow occluded to deplete muscle PCr stores. Exercise was performed following 7 days consumption of low-fat (LF) or high-fat (HF) diets. Immediately following exercise, blood flow was reinstated, and muscle was sampled after 20, 60, and 120 seconds of recovery. Mitochondrial coupling was assessed by determining the rate of PCr resynthesis during recovery. The HF diet increased UCP3 protein content by approximately 44% compared with the LF diet. However, this HF diet-induced increase in UCP3 expression was not associated with any changes in the rate of muscle PCr resynthesis during conditions of maximal flux through oxidative phosphorylation. Muscle acetylcarnitine, free-creatine, and lactate concentrations during recovery were unaffected by the HF diet. Taken together, our findings demonstrate that increasing muscle UCP3 expression does not diminish the rate of PCr resynthesis, allowing us to conclude that the primary role of UCP3 in humans is not uncoupling.

The Time Course of Haemodynamic, Autonomic and Skeletal Muscle Metabolic Abnormalities Following First Extensive Myocardial Infarction in Man

We investigated the time course of genesis of skeletal muscle dysfunction and sympatho-vagal imbalance after myocardial infarction.We studied 22 normal controls, 22 patients with >6 months stable chronic heart failure and 10 patients after a first massive myocardial infarction at 1–3 weeks (the “eary” period), 6–8 weeks (“mid”) and 6–9 months (“late”) following their infarct. Four patients developed overt heart failure. Forearm muscle metabolism was stuided using31P magnetic resonance spectroscopy (MRS). Sympatho-vagal balance was assessed by heart rate variability and radiolabelled norepinephrine kinetics.Increased norepinephrine spillover (0.55±0.02 v 0.27±0.04 mg/min/m2P<0.01) and decreased heart rate variability were confined to those post-myocardial infarction patients who subsequently developed heart failure. Resting cardiac output was normal in all the post-myocardial infarction patients, although the response of cardiac output to supine bicycle exercise at the “mid” study point was less in the group who subsequently developed heart failure (9±1 v 41±8%P<0.005). In the MRS studies, there were no detectable differences between those who did or did not develop heart failure. The initial rate of ATP turnover, calculated from initial-exercise changes in pH and phosphocreatine (PCr), was increased in established chronic heart failure, but in the post-myocardial infarction patients a numerically similar increase reached statistical significance only in the early group (19±3 v 11±1 m m/minP <0.005). The apparent maximum rate of oxidative ATP synthesis, calculated from post-exercise PCr recovery kinetics, was lower than control in the late post-myocardial infarction and established chronic heart failure groups 34±5 v 55±4 m m/min P<0.03 and 38±3 v 55±4 m m/minP <0.003, respectively).Skeletal muscle metabolism and autonomic function become abnormal after an extensive myocardial infarction. While skeletal muscle abnormalities are relatively slow to develop and unrelated to the degree of failure, excessive neurohormonal activation and impaired cardiac output response to exercise seem from an early stage to characterize patients who subsequently develop chronic heart failure.

Quantitative analysis of skeletal muscle bioenergetics and proton efflux in migraine and cluster headache

Phosphorus MR spectroscopy ( 31P-MRS) was used to quantify skeletal muscle bioenergetics and proton efflux in 63 patients with migraine (23 with migraine without aura, MwoA, 22 with migraine with aura, MwA, and 18 with prolonged aura or smoke, CM) and in 14 patients with cluster headache (CH), all in an attack-free period. At rest mitochondrial function was abnormal only in CM, as shown by a low phosphocreatine (PCr) concentration. At the end of a mixed glycolytic/aerobic exercised all three migraine groups showed a significantly smaller decrease of cytosolic pH compared to controls with a similar end-exercise PCr breakdown, while end-exercise pH was normal in cluster headache patients. The normal rate of proton efflux in all headache groups suggests that the reduced end-exercise acidification was due to a reduction of glycolytic flux in migraine patients. The maximum rate of mitochondrial ATP production ( Q max), calculated from the rate of post-exercise PCr recovery and the end-exercise [ADP], was low in cluster headache patients as well as in migraine patients except MwoA. In migraine the degree of the mitochondrial impairement, that apparently is associated with a reduced glycolytic flux, is related to the severity of the clinical phenotype. © 1997 Eseevier Science B.V. All rights reserved.

Reduced oxidative muscle metabolism in chronic fatigue syndrome

The purpose of this study was to determine if chronic fatigue syndrome (CSF) is characterized by abnormalities in oxidative muscle metabolism. Patients with CFS according to Centers for Disease Control (CDC) criteria (n = 22) were compared to normal sedentary subjects (n = 15). CFS patients were also tested before and 2 days after a maximal treadmill test. Muscle oxidative capacity was measured as the maximal rate of postexercise phosphocreatine (PCr) resynthesis using the ADP model (Vmax) in the calf muscles using 31P magnetic resonance spectroscopy. Vmax was significantly reduced in CFS patients (39.6 +/- 2.8 mmol/L/min, mean +/- SE) compared to controls (53.8 +/- 2.8 mmol/L/min). Two days postexercise there was no change in resting inorganic phosphate (Pi)/PCr or Vmax in the CFS patients (n = 14). In conclusion, oxidative metabolism is reduced in CFS patients compared to sedentary controls. In addition, a single bout of strenuous exercise did not cause a further reduction in oxidative metabolism, or alter resting Pi/PCr ratios.