The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
George K Radda - One of the best experts on this subject based on the ideXlab platform.
-
Skeletal Muscle Metabolism in Uremic Rats: A 31P-Magnetic Resonance Study
Nephron, 2008Co-Authors: Campbell H. Thompson, Graham J. Kemp, George K Radda, Y Green, J. G. G. LedinghamAbstract:The effect of uremia on Skeletal Muscle Metabolism of the rat was examined using 31P-magnetic resonance spectroscopy. Three weeks following either a 5/6 nephrectomy or a sham operation, Wistar rats were placed in a 7T magnet, and the sciatic nerve was stimulated for 10 min. Analysis of spectra allowed calculation of intracellular pH and the relative concentrations of phosphocreatine (PCr), inorganic phosphate (Pi) and ATP. [ADP] was calculated from the creatine kinase equilibrium. There was a significant reduction in the resting intracellular [Pi] despite an elevation in extracellular [Pi], probably due to a reduction in the activity of the membrane Na/Pi cotransporter on account of a reduced sodium gradient. Despite anemia and uremia, there were no significant metabolic abnormalities during exercise and recovery accompanying this substantial reduction in glomerular filtration rate implying that at this level of renal impairment, there is no mitochondrial dysfunction.
-
The effect of propionyl L-carnitine on Skeletal Muscle Metabolism in renal failure.
Clinical Nephrology, 1997Co-Authors: Campbell H. Thompson, A. B. Irish, Graham J. Kemp, D.j. Taylor, George K RaddaAbstract:The effect of propionyl L-carnitine on Skeletal Muscle Metabolism in chronic renal failure. Carnitine deficiency, resulting in defective oxidative ATP synthesis, has been implicated in the myopathy of chronic renal failure. Using 31 P magnetic resonance spectroscopy we examined calf Muscle Metabolism in 10 dialysed patients before and after 8 weeks of propionyl L-carnitine (PLC) 2 g p. o. daily. Resting phosphocreatine/ATP (4.41 ± 0.20 [SEM ] ) decreased to normal control levels on PLC (3.98 ± 0.14; controls 4.00 ± 0.06). In contrast, there was no effect of PLC on aerobic and anaerobic Metabolism of Muscle during or following 2-10 min exercise. The maximal calculated oxidative capacity (Q max ) remained below normal (28 ± 3 mM/min before and 24 ± 3 mM/min after PLC; controls 49 ± 3 mM/min). Q max correlated positively with hemoglobin concentration ([Hb]) after PLC (p 10 g/dl. [Hb] was rate limiting to oxidative Metabolism in recovery from exercise but only following treatment with PLC. Patients with anemia or those subjects who use relatively more non-oxidatively synthesized ATP during exercise, do not respond to PLC. Oxidative Metabolism did not normalize on PLC suggesting that anemia and carnitine deficiency are not the only causes of mitochondrial dysfunction in renal failure.
-
Skeletal Muscle Metabolism before and after gemfibrozil treatment in dialysed patients with chronic renal failure
Clinical Nephrology, 1996Co-Authors: Campbell H. Thompson, A. B. Irish, Graham J. Kemp, D.j. Taylor, George K RaddaAbstract:Patients with chronic renal failure appear at greater risk for Skeletal Muscle side effects from the fibric acid group of lipid lowering agents. In order to determine whether sub-clinical defects of Skeletal Muscle Metabolism can be detected in dyslipidaemic dialysis-dependent patients receiving fibrates, we studied nine patients before and after three months of gemfibrozil therapy (300-600 mg daily). Aerobic and anaerobic Metabolism of the right calf Muscle was examined at rest and during exercise using 31 P magnetic resonance spectroscopy. Near infra-red spectroscopy was used to assess Skeletal Muscle re-oxygenation following ischaemic exercise of the arm. Following gemfibrozil treatment, plasma triglycerides fell significantly 3.0 ± 0.5 mM (SEM) to 1.5 ± 0.2 mM. Gemfibrozil did not affect the established metabolic defects that exist in the Skeletal Muscle of the dialysed patient. Skeletal Muscle re-oxygenation was not significantly lower in renal failure and was not altered by gemfibrozil. Gemfibrozil (600 mg daily) significantly improved the lipid profile of chronic renal failure and was not associated with clinical or bioenergetic impairment of Skeletal Muscle Metabolism.
-
Skeletal Muscle Metabolism in Heart Failure
Creatine and Creatine Phosphate, 1996Co-Authors: M Conway, Bheeshma Rajagopalan, George K RaddaAbstract:This chapter discusses the Skeletal Muscle Metabolism in heart failure. A greater understanding of the mechanism underlying fatigue and reduced exercise tolerance has been gleaned from Skeletal Muscle Metabolism studies in patients with heart failure using 31 P Magnetic Resonance Spectroscopy ( 31 P MRS). Further application of the technique in association with innovative physiological, biopsy, and molecular biological studies should further elucidate the mechanisms of symptoms for which the clinician, in the out-patients' department, often has little to offer. The discovery of changes in creatine phosphate (PCr) Metabolism raises the possibility that creatine and PCr therapy may have a role in the future management of these patients. Whether these agents will be adequate on their own, or whether administration in combination with “facilitator” agents will be required is still unclear. However, the observation of biochemical abnormalities in vivo which are central to, or at least a marker of, inefficient Muscle biochemistry Metabolism presents a promising avenue of investigation approach and commence the next millennium.
-
Rat Skeletal Muscle Metabolism in experimental heart failure: effects of physical training
Acta Physiologica Scandinavica, 1995Co-Authors: Franois Brunotte, Campbell H. Thompson, Stamatis Adamopoulos, John F. Unitt, Dc Lindsay, Andrew J S Coats, Loukas Kaklamanis, George K Radda, Bheeshma RajagopalanAbstract:Skeletal Muscle metabolic abnormalities exist in chronic heart failure. The influence of physical training on Muscle Metabolism after myocardial infarction was studied in a rat model. 31 P magnetic resonance spectroscopy and enzyme assays were performed in Wistar rats 12 weeks after coronary artery ligation. Infarcted rats were allocated randomly to either 6 weeks of training or non-training. Spectra were collected from the calf Muscles during sciatic nerve stimulation at 2 Hz. Fibre typing and enzymatic assays were performed on the Muscles of the contralateral non stimulated leg. Post-mortem rats were also divided into severe and moderate heart failure according to the lung weight per body weight. At 200 g twitch tension, phosphocreatine and pH were found to be significantly lower in the non-trained severe heart failure group compared with the other groups. Phosphocreatine recovery half-time was significantly longer in the non-trained group with severe heart failure and correlated with the citrate synthase activity in the Muscle. The training did not induce a change in the enzyme activities in the infarcted animals with moderate heart failure but did correct the lower citrate synthase activity in the non-trained severe heart failure animals. This normalization of Muscle Metabolism was achieved by training without any change in calf Muscle mass, making atrophy unlikely to be the sole cause of the metabolic changes in heart failure. Training in rats with severe heart failure can reverse the abnormalities of Skeletal Muscle Metabolism, implicating decreased physical activity in the aetiology of these changes.
Campbell H. Thompson - One of the best experts on this subject based on the ideXlab platform.
-
Skeletal Muscle Metabolism in Uremic Rats: A 31P-Magnetic Resonance Study
Nephron, 2008Co-Authors: Campbell H. Thompson, Graham J. Kemp, George K Radda, Y Green, J. G. G. LedinghamAbstract:The effect of uremia on Skeletal Muscle Metabolism of the rat was examined using 31P-magnetic resonance spectroscopy. Three weeks following either a 5/6 nephrectomy or a sham operation, Wistar rats were placed in a 7T magnet, and the sciatic nerve was stimulated for 10 min. Analysis of spectra allowed calculation of intracellular pH and the relative concentrations of phosphocreatine (PCr), inorganic phosphate (Pi) and ATP. [ADP] was calculated from the creatine kinase equilibrium. There was a significant reduction in the resting intracellular [Pi] despite an elevation in extracellular [Pi], probably due to a reduction in the activity of the membrane Na/Pi cotransporter on account of a reduced sodium gradient. Despite anemia and uremia, there were no significant metabolic abnormalities during exercise and recovery accompanying this substantial reduction in glomerular filtration rate implying that at this level of renal impairment, there is no mitochondrial dysfunction.
-
The effect of propionyl L-carnitine on Skeletal Muscle Metabolism in renal failure.
Clinical Nephrology, 1997Co-Authors: Campbell H. Thompson, A. B. Irish, Graham J. Kemp, D.j. Taylor, George K RaddaAbstract:The effect of propionyl L-carnitine on Skeletal Muscle Metabolism in chronic renal failure. Carnitine deficiency, resulting in defective oxidative ATP synthesis, has been implicated in the myopathy of chronic renal failure. Using 31 P magnetic resonance spectroscopy we examined calf Muscle Metabolism in 10 dialysed patients before and after 8 weeks of propionyl L-carnitine (PLC) 2 g p. o. daily. Resting phosphocreatine/ATP (4.41 ± 0.20 [SEM ] ) decreased to normal control levels on PLC (3.98 ± 0.14; controls 4.00 ± 0.06). In contrast, there was no effect of PLC on aerobic and anaerobic Metabolism of Muscle during or following 2-10 min exercise. The maximal calculated oxidative capacity (Q max ) remained below normal (28 ± 3 mM/min before and 24 ± 3 mM/min after PLC; controls 49 ± 3 mM/min). Q max correlated positively with hemoglobin concentration ([Hb]) after PLC (p 10 g/dl. [Hb] was rate limiting to oxidative Metabolism in recovery from exercise but only following treatment with PLC. Patients with anemia or those subjects who use relatively more non-oxidatively synthesized ATP during exercise, do not respond to PLC. Oxidative Metabolism did not normalize on PLC suggesting that anemia and carnitine deficiency are not the only causes of mitochondrial dysfunction in renal failure.
-
Skeletal Muscle Metabolism before and after gemfibrozil treatment in dialysed patients with chronic renal failure
Clinical Nephrology, 1996Co-Authors: Campbell H. Thompson, A. B. Irish, Graham J. Kemp, D.j. Taylor, George K RaddaAbstract:Patients with chronic renal failure appear at greater risk for Skeletal Muscle side effects from the fibric acid group of lipid lowering agents. In order to determine whether sub-clinical defects of Skeletal Muscle Metabolism can be detected in dyslipidaemic dialysis-dependent patients receiving fibrates, we studied nine patients before and after three months of gemfibrozil therapy (300-600 mg daily). Aerobic and anaerobic Metabolism of the right calf Muscle was examined at rest and during exercise using 31 P magnetic resonance spectroscopy. Near infra-red spectroscopy was used to assess Skeletal Muscle re-oxygenation following ischaemic exercise of the arm. Following gemfibrozil treatment, plasma triglycerides fell significantly 3.0 ± 0.5 mM (SEM) to 1.5 ± 0.2 mM. Gemfibrozil did not affect the established metabolic defects that exist in the Skeletal Muscle of the dialysed patient. Skeletal Muscle re-oxygenation was not significantly lower in renal failure and was not altered by gemfibrozil. Gemfibrozil (600 mg daily) significantly improved the lipid profile of chronic renal failure and was not associated with clinical or bioenergetic impairment of Skeletal Muscle Metabolism.
-
Rat Skeletal Muscle Metabolism in experimental heart failure: effects of physical training
Acta Physiologica Scandinavica, 1995Co-Authors: Franois Brunotte, Campbell H. Thompson, Stamatis Adamopoulos, John F. Unitt, Dc Lindsay, Andrew J S Coats, Loukas Kaklamanis, George K Radda, Bheeshma RajagopalanAbstract:Skeletal Muscle metabolic abnormalities exist in chronic heart failure. The influence of physical training on Muscle Metabolism after myocardial infarction was studied in a rat model. 31 P magnetic resonance spectroscopy and enzyme assays were performed in Wistar rats 12 weeks after coronary artery ligation. Infarcted rats were allocated randomly to either 6 weeks of training or non-training. Spectra were collected from the calf Muscles during sciatic nerve stimulation at 2 Hz. Fibre typing and enzymatic assays were performed on the Muscles of the contralateral non stimulated leg. Post-mortem rats were also divided into severe and moderate heart failure according to the lung weight per body weight. At 200 g twitch tension, phosphocreatine and pH were found to be significantly lower in the non-trained severe heart failure group compared with the other groups. Phosphocreatine recovery half-time was significantly longer in the non-trained group with severe heart failure and correlated with the citrate synthase activity in the Muscle. The training did not induce a change in the enzyme activities in the infarcted animals with moderate heart failure but did correct the lower citrate synthase activity in the non-trained severe heart failure animals. This normalization of Muscle Metabolism was achieved by training without any change in calf Muscle mass, making atrophy unlikely to be the sole cause of the metabolic changes in heart failure. Training in rats with severe heart failure can reverse the abnormalities of Skeletal Muscle Metabolism, implicating decreased physical activity in the aetiology of these changes.
-
physical training improves Skeletal Muscle Metabolism in patients with chronic heart failure
Journal of the American College of Cardiology, 1993Co-Authors: Campbell H. Thompson, Franois Brunotte, Stamatis Adamopoulos, Leonard F Arnolda, T E Meyer, Andrew J S Coats, Jeff F Dunn, John R StrattonAbstract:Objectives. This study investigated the effects of physical training on Skeletal Muscle Metabolism in patients with chronic heart failure. Background. Skeletal Muscle metabolic abnormalities in patients with chronic heart failure have been associated with exercise intolerance. Muscle deconditioning is a possible mechanism for the intrinsic Skeletal Muscle metabolic changes seen in chronic heart failure. Methods. We used phosphorus-31 nuclear magnetic resonance spectroscopy to study Muscle Metabolism during exercise in 12 patients with stable ischemic chronic heart failure undergoing 8 weeks of home-based bicycle exercise training in a randomized crossover controlled trial. Changes in Muscle pH and concentrations of phosphocreatine and adenosine diphosphate (ADP) were measured in phosphorus-31 spectra of calf Muscle obtained at rest, throughout incremental work load plantar flexion until exhaustion and during recovery from exercise. Results were compared with those in 15 age-matched control subjects who performed a single study only. Results. Before training, phosphocreatine depletion, Muscle acidification and the increase in ADP during the 1st 4 min of plantar flexion exercise were all increased (p < 0.04) compared with values in control subjects. Training produced an increase (p < 0.002) in incremental plantar flexion exercise tolerance. After training, phosphocreatine depletion and the increase in ADP during exercise were reduced significantly (p < 0.003) at all matched submaximal work loads and at peak exercise, although there was no significant change in the response of Muscle pH to exercise. After training, changes in ADP were not significantly different from those in control subjects, although phosphocreatine depletion was still greater (p < 0.05) in trained patients than in control subjects. The phosphocreatine recovery half-time was significantly (p < 0.05) shorter after training, althrough there was no significant change in the half-time of adenosine diphosphate recovery. In untrained subjects, the initial rate of phosphocreatine resynthesis after exercise (a measure of the rate of oxidative adenosine triphosphate [ATP]synthesis) and the inferred maximal rate of mitochondrial ATP synthesis were reduced compared with rates in control subjects (p < 0.003) and both were significantly increased (p < 0.05) by training, so that they were not significantly different from values in control subjects. Conclusions. The reduction in phosphocreatine depletion and in the increase in ADP during exercise, and the enhanced rate of phosphocreatine resynthesis in recovery (which is independent of Muscle mass) indicate that a substantial correction of the impaired oxidative capacity of Skeletal Muscle in chronic heart failure can be achieved by exercise training.
Stamatis Adamopoulos - One of the best experts on this subject based on the ideXlab platform.
-
Rat Skeletal Muscle Metabolism in experimental heart failure: effects of physical training
Acta Physiologica Scandinavica, 1995Co-Authors: Franois Brunotte, Campbell H. Thompson, Stamatis Adamopoulos, John F. Unitt, Dc Lindsay, Andrew J S Coats, Loukas Kaklamanis, George K Radda, Bheeshma RajagopalanAbstract:Skeletal Muscle metabolic abnormalities exist in chronic heart failure. The influence of physical training on Muscle Metabolism after myocardial infarction was studied in a rat model. 31 P magnetic resonance spectroscopy and enzyme assays were performed in Wistar rats 12 weeks after coronary artery ligation. Infarcted rats were allocated randomly to either 6 weeks of training or non-training. Spectra were collected from the calf Muscles during sciatic nerve stimulation at 2 Hz. Fibre typing and enzymatic assays were performed on the Muscles of the contralateral non stimulated leg. Post-mortem rats were also divided into severe and moderate heart failure according to the lung weight per body weight. At 200 g twitch tension, phosphocreatine and pH were found to be significantly lower in the non-trained severe heart failure group compared with the other groups. Phosphocreatine recovery half-time was significantly longer in the non-trained group with severe heart failure and correlated with the citrate synthase activity in the Muscle. The training did not induce a change in the enzyme activities in the infarcted animals with moderate heart failure but did correct the lower citrate synthase activity in the non-trained severe heart failure animals. This normalization of Muscle Metabolism was achieved by training without any change in calf Muscle mass, making atrophy unlikely to be the sole cause of the metabolic changes in heart failure. Training in rats with severe heart failure can reverse the abnormalities of Skeletal Muscle Metabolism, implicating decreased physical activity in the aetiology of these changes.
-
physical training improves Skeletal Muscle Metabolism in patients with chronic heart failure
Journal of the American College of Cardiology, 1993Co-Authors: Campbell H. Thompson, Franois Brunotte, Stamatis Adamopoulos, Leonard F Arnolda, T E Meyer, Andrew J S Coats, Jeff F Dunn, John R StrattonAbstract:Objectives. This study investigated the effects of physical training on Skeletal Muscle Metabolism in patients with chronic heart failure. Background. Skeletal Muscle metabolic abnormalities in patients with chronic heart failure have been associated with exercise intolerance. Muscle deconditioning is a possible mechanism for the intrinsic Skeletal Muscle metabolic changes seen in chronic heart failure. Methods. We used phosphorus-31 nuclear magnetic resonance spectroscopy to study Muscle Metabolism during exercise in 12 patients with stable ischemic chronic heart failure undergoing 8 weeks of home-based bicycle exercise training in a randomized crossover controlled trial. Changes in Muscle pH and concentrations of phosphocreatine and adenosine diphosphate (ADP) were measured in phosphorus-31 spectra of calf Muscle obtained at rest, throughout incremental work load plantar flexion until exhaustion and during recovery from exercise. Results were compared with those in 15 age-matched control subjects who performed a single study only. Results. Before training, phosphocreatine depletion, Muscle acidification and the increase in ADP during the 1st 4 min of plantar flexion exercise were all increased (p < 0.04) compared with values in control subjects. Training produced an increase (p < 0.002) in incremental plantar flexion exercise tolerance. After training, phosphocreatine depletion and the increase in ADP during exercise were reduced significantly (p < 0.003) at all matched submaximal work loads and at peak exercise, although there was no significant change in the response of Muscle pH to exercise. After training, changes in ADP were not significantly different from those in control subjects, although phosphocreatine depletion was still greater (p < 0.05) in trained patients than in control subjects. The phosphocreatine recovery half-time was significantly (p < 0.05) shorter after training, althrough there was no significant change in the half-time of adenosine diphosphate recovery. In untrained subjects, the initial rate of phosphocreatine resynthesis after exercise (a measure of the rate of oxidative adenosine triphosphate [ATP]synthesis) and the inferred maximal rate of mitochondrial ATP synthesis were reduced compared with rates in control subjects (p < 0.003) and both were significantly increased (p < 0.05) by training, so that they were not significantly different from values in control subjects. Conclusions. The reduction in phosphocreatine depletion and in the increase in ADP during exercise, and the enhanced rate of phosphocreatine resynthesis in recovery (which is independent of Muscle mass) indicate that a substantial correction of the impaired oxidative capacity of Skeletal Muscle in chronic heart failure can be achieved by exercise training.
Cristi L. Galindo - One of the best experts on this subject based on the ideXlab platform.
-
GRMD cardiac and Skeletal Muscle Metabolism gene profiles are distinct
BMC Medical Genomics, 2017Co-Authors: Larry W. Markham, Candice L. Brinkmeyer-langford, Jonathan H. Soslow, Manisha Gupte, Douglas B. Sawyer, Joe N. Kornegay, Cristi L. GalindoAbstract:Background Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, which codes for the dystrophin protein. While progress has been made in defining the molecular basis and pathogenesis of DMD, major gaps remain in understanding mechanisms that contribute to the marked delay in cardiac compared to Skeletal Muscle dysfunction. Methods To address this question, we analyzed cardiac and Skeletal Muscle tissue microarrays from golden retriever muscular dystrophy (GRMD) dogs, a genetically and clinically homologous model for DMD. A total of 15 dogs, 3 each GRMD and controls at 6 and 12 months plus 3 older (47–93 months) GRMD dogs, were assessed. Results GRMD dogs exhibited tissue- and age-specific transcriptional profiles and enriched functions in Skeletal but not cardiac Muscle, consistent with a “metabolic crisis” seen with DMD microarray studies. Most notably, dozens of energy production-associated molecules, including all of the TCA cycle enzymes and multiple electron transport components, were down regulated. Glycolytic and glycolysis shunt pathway-associated enzymes, such as those of the anabolic pentose phosphate pathway, were also altered, in keeping with gene expression in other forms of Muscle atrophy. On the other hand, GRMD cardiac Muscle genes were enriched in nucleotide Metabolism and pathways that are critical for neuromuscular junction maintenance, synaptic function and conduction. Conclusions These findings suggest differential metabolic dysfunction may contribute to distinct pathological phenotypes in Skeletal and cardiac Muscle.
James R Sowers - One of the best experts on this subject based on the ideXlab platform.
-
the metabolic syndrome role of Skeletal Muscle Metabolism
Annals of Medicine, 2006Co-Authors: Craig S Stump, Erik J Henriksen, James R SowersAbstract:Skeletal Muscle constitutes the largest insulin‐sensitive tissue in the body and is the primary site for insulin‐stimulated glucose utilization. Skeletal Muscle resistance to insulin is fundamental to the metabolic dysregulation associated with obesity and physical inactivity, and contributes to the development of the metabolic syndrome (MS). The inability to efficiently take up and store fuel, and to transition from fat to glucose as the primary source of fuel during times of caloric abundance (high insulin) or scarcity (low insulin) has been termed metabolic inflexibility which contributes to a whole body metabolic dysregulation and cardiovascular risk. Potential mechanisms contributing to reduced insulin signaling and action in Skeletal Muscle includes adipose tissue expansion and increased inflammatory adipokines, increased renin‐angiotensin‐aldosterone system (RAAS) activity, decreases in Muscle mitochondrial oxidative capacity, increased intramuscular lipid accumulation, and increased reactive oxyge...