phosphocreatine and Anemia

Adult male Sprague-Dawley rats were randomly assigned to two groups: control and anaemic. Anaemia was induced by periodical blood withdrawal. Extensor digitorum longus and soleus muscles were excised under pentobarbital sodium total anaesthesia and processed for transmission electron microscopy, histochemical and biochemical analyses. Mitochondrial volume was determined by transmission electron microscopy in three different regions of each muscle fibre: pericapillary, sarcolemmal and sarcoplasmatic. Muscle samples sections were also stained with histochemical methods (SDH and m-ATPase) to reveal the oxidative capacity and shortening velocity of each muscle fibre. Determinations of fibre and capillary densities and fibre type composition were made from micrographs of different fixed fields selected in the equatorial region of each rat muscle. Determination of metabolites (ATP, inorganic phosphate, creatine, creatine phosphate and lactate) was done using established enzymatic methods and spectrophotometric detection. Significant differences in mitochondrial volumes were found between pericapillary, sarcolemmal and sarcoplasmic regions when data from animal groups were tested independently. Moreover, it was verified that anaemic rats had significantly lower values than control animals in all the sampled regions of both muscles. These changes were associated with a significantly higher proportion of fast fibres in anaemic rat soleus muscles (slow oxidative group = 63.8%; fast glycolytic group = 8.2%; fast oxidative glycolytic group = 27.4%) than in the controls (slow oxidative group = 79.0%; fast glycolytic group = 3.9%; fast oxidative glycolytic group = 17.1%). No significant changes were detected in the extensor digitorum longus muscle. A significant increase was found in metabolite concentration in both the extensor digitorum longus and soleus muscles of the anaemic animals as compared to the control group. In conclusion, hypoxaemic hypoxia causes a reduction in mitochondrial volumes of pericapillary, sarcolemmal, and sarcoplasmic regions. However, a common proportional pattern of the zonal distribution of mitochondria was maintained within the fibres. A significant increment was found in the concentration of some metabolites and in the proportion of fast fibres in the more oxidative soleus muscle in contrast to the predominantly anaerobic extensor digitorum longus.

Topics: Adenosine Triphosphate; Anemia; Animals; Capillaries; Creatine; Histocytochemistry; Hypoxia; Lactic Acid; Male; Microscopy, Electron, Transmission; Mitochondria, Muscle; Muscle Contraction; Muscle Fibers, Fast-Twitch; Muscle Fibers, Slow-Twitch; Muscle, Skeletal; Phosphates; Phosphocreatine; Random Allocation; Rats; Rats, Sprague-Dawley

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 31P 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 (Qmax) remained below normal (28 +/- 3 mM/min before and 24 +/- 3 mM/min after PLC; controls 49 +/- 3 mM/min). Qmax correlated positively with hemoglobin concentration ([Hb]) after PLC (p < 0.03). Oxidative capacity assessed by phosphocreatine recovery T significantly improved with PLC administration (0.93 +/- 0.1 to 0.74 +/- 0.08 min) in those patients (n = 6) with [Hb] > 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.

Topics: Adenosine Triphosphate; Anemia; Carnitine; Exercise; Female; Hemoglobins; Humans; Kidney Failure, Chronic; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mitochondria, Muscle; Muscle, Skeletal; Oxygen Consumption; Peritoneal Dialysis, Continuous Ambulatory; Phosphocreatine; Renal Dialysis

Fatigue and lethargy, common symptoms in uraemia, have been attributed to many factors. To assess possible bioenergetic contributions to this, we examined the forearm muscle of five patients in end-stage renal failure using 31P-magnetic resonance spectroscopy. There was a small increase in the ratio of intracellular inorganic phosphate to ATP in resting muscle, suggesting an increased cytosolic phosphate concentration. During exercise, increased phosphocreatine breakdown was accompanied by rapid intracellular acidification and an increase in calculated lactic acid accumulation in the muscle of the uraemic subjects, suggesting glycolysis dominating over oxidative phosphorylation as a source of ATP. After exercise, the half-time of phosphocreatine (PCr) recovery was longer in the uraemic subjects, suggesting diminished mitochondrial function. The initial rate of PCr resynthesis was not significantly decreased, but when account was taken of the high cytosolic ADP concentration (which drives mitochondrial oxidative ATP synthesis) the calculated maximum oxidative capacity was significantly reduced in the uraemic subjects. Thus there was evidence of mitochondrial dysfunction in uraemia due either to limitation of oxygen supply, reduced mitochondrial content, or an intrinsic mitochondrial defect. This resulted in increased phosphocreatine depletion and increased glycolytic ATP production during exercise and there was partial compensation of the mitochondrial abnormality by increased ADP concentration. In three of these patients studied after elevation of haemoglobin with erythropoeitin (from 8 to 12 g/dl), initial phosphocreatine breakdown and lactic acid accumulation during exercise were normalized, while exercise duration and calculated maximum oxidative capacity remained significantly abnormal. This suggests that anaemia contributes to these metabolic abnormalities but does not fully explain them.

Topics: Adenosine Triphosphate; Aged; Anemia; Chronic Disease; Energy Metabolism; Exercise; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Lactates; Lactic Acid; Male; Middle Aged; Muscles; Phosphocreatine; Uremia

It has been demonstrated in experiments on 134 cats that during acute blood loss (24 +/- 0.8 ml/kg), hyperbaric oxygen therapy (3039 hPa, 60 min) stimulates cytochrome oxidase, eliminates compensatory activation of mitochondrial creatine kinase and maintains the hyperactivity of cytoplasmic creatine kinase in the diencephalon, stabilizes the elevated AMP content at the level of blood loss compensation stage, prevents the fall in pO2 and in the ATP level as well as that in the energy charge and creatine phosphate content in the sensomotor cortex and subcortex, that is typical for the decompensation stage. Besides, hyperbaric oxygen therapy also averts the development of the terminal state that supervenes in the majority of untreated animals.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphatases; Adenosine Triphosphate; Anemia; Animals; Bloodletting; Ca(2+) Mg(2+)-ATPase; Cats; Electron Transport Complex IV; Energy Metabolism; Female; Hyperbaric Oxygenation; Hypothalamus; Male; Phosphocreatine; Somatosensory Cortex; Thalamus

The red blood cells of chicken have a lower creatine concentration than those of man (1 mg/100 ml vs 5-6 mg/100 ml cells). No creatine phosphate was found in either erythrocytes or reticulocytes. With anemia produced by phenylhydrazine and bleeding a young cell population appeared with a higher creatine concentration.

Topics: Anemia; Animals; Bloodletting; Chickens; Creatine; Erythrocytes; Erythropoiesis; Hydrolysis; Phenylhydrazines; Phosphocreatine; Plasma

Topics: Acidosis; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Anemia; Animals; Asphyxia; Brain; Brain Diseases; Carbon Dioxide; Dogs; Energy Metabolism; Glucose; Hemoglobins; Humans; Hypoxia; Ischemia; Ischemic Attack, Transient; Lactates; Oxygen; Oxygen Consumption; Partial Pressure; Phosphocreatine; Rats; Time Factors

Topics: Adenosine Triphosphate; Anemia; Anesthesia, Conduction; Anesthetics; Animals; Blood Chemical Analysis; Brain Chemistry; Carbon Dioxide; Cerebral Cortex; Dogs; Electroencephalography; Halothane; Hypothermia, Induced; Hypoxia, Brain; Lactates; Nitrous Oxide; Oxygen Consumption; Phosphocreatine; Pyruvates; Thiopental

Topics: Adolescent; Anemia; Anemia, Hypochromic; Coenzymes; Fructose-Bisphosphate Aldolase; Geriatrics; Humans; Muscular Diseases; Muscular Dystrophies; Neurotic Disorders; Pharmacology; Phosphocreatine; Respiratory Tract Diseases; Urology