phosphocreatine and Metabolic-Diseases

Malignant hyperthermia (MH) is a metabolic myopathy with an abnormal release of calcium by the sarcoplasmic reticulum (SR), triggered by volatile anesthetics and succinylcholine. Similarly, caffeine enhances Ca(2+)release by the SR in vitro. In a prospective, randomized study, high-energy phosphates were studied by intramuscular 31-phosphorus magnetic resonance spectroscopy ((31)P-MRS) in 10 MH-susceptible (MHS) and 7 MH-nonsusceptible (MHN) subjects before and after injection of 0.5 ml caffeine (20 mM). Intramuscular energy balance, measured by the ratios of P(i)/PCr and P(i)/gamma-ATP, did not differ between MHS and MHN patients before and after intramuscular caffeine injection. However, within each group, P(i)/PCr and P(i)/gamma-ATP increased significantly only in the MHS group. Intramuscular caffeine injection seemed to impair the metabolic balance in MHS individuals. This may reflect a local calcium overload leading to consumption of high-energy phosphates and increase of inorganic phosphate. Intramuscular stimulation by caffeine and (31)P-MRS may provide a valuable tool to investigate MH-related metabolic disturbances.

Topics: Adult; Age Factors; Caffeine; Calcium; Calcium Signaling; Disease Susceptibility; Female; Humans; Injections, Intramuscular; Magnetic Resonance Spectroscopy; Male; Malignant Hyperthermia; Metabolic Diseases; Middle Aged; Muscle, Skeletal; Muscular Diseases; Oxidative Phosphorylation; Phosphocreatine; Phosphorus; Phosphorus Radioisotopes; Prospective Studies; Radionuclide Imaging; Sex Factors

The hypothesis that brain mitochondria are directly affected in several phenotypes associated with disordered oxidative phosphorylation was tested using phosphorus 31 (31P) magnetic resonance spectroscopy. Abnormal phosphorylation potentials in skeletal muscle have been demonstrated by 31P magnetic resonance spectroscopy in patients with mitochondrial cytopathies (heritable disorders of oxidative phosphorylation), but abnormalities of phosphorylation potentials in other organs have not been documented. Several lines of evidence suggest that these mutations may affect mitochondria in nonmuscle tissue. In this study we found that phosphocreatine-to-ATP ratios in brain were significantly reduced and that calculated brain ADP concentrations, phosphorylation potentials, and percentage of maximal rate of ATP synthesis were significantly altered in the 5 patients examined. This study indicates a primary abnormality of mitochondrial function in the brain, even in the absence of clinically evident cerebral dysfunction.

Topics: Adenosine Triphosphate; Adult; Brain; Child; Humans; Magnetic Resonance Spectroscopy; Metabolic Diseases; Mitochondria; Phosphocreatine

Abnormal mitochondria are an increasingly recognized cause of neuromuscular disease. We have used phosphorus magnetic resonance spectroscopy to monitor noninvasively the metabolism of high-energy phosphates and the intracellular pH of human skeletal muscle in vivo in 12 patients with mitochondrial myopathy. At rest, an abnormality could be demonstrated in 11 of 12 patients. Ten patients had evidence of a reduced muscle energy state with at least one of the following abnormalities: low phosphorylation potential, low phosphocreatine concentration, high adenosine diphosphate concentration, or high inorganic phosphate concentration. Two patients had abnormal resting muscle intracellular pH. In some patients phosphocreatine concentration decreased to low values during exercise despite limited work output. This was not accompanied by particularly severe intracellular acidosis. Evidence of impaired rephosphorylation of adenosine diphosphate to adenosine triphosphate during recovery from exercise was found in approximately half the patients. Phosphorus magnetic resonance spectroscopy is useful in the noninvasive diagnosis of mitochondrial myopathies and in defining the pathophysiological basis of these disorders.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adolescent; Adult; Aged; Female; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Metabolic Diseases; Middle Aged; Mitochondria, Muscle; Muscles; Muscular Diseases; Phosphocreatine; Phosphorus

Insulin completely suppressed creatinuria in rats x-irradiated with an absorbed dose of 500 rads. The hormone may exert this effect either by restoring or maintaining the ability of irradiated muscle to take up creatine from the extra-cellular fluid at a normal rate, or possibly by influencing the synthesis or breakdown of phosphorylcreatine.

Topics: Animals; Creatine; Extracellular Space; Insulin; Male; Metabolic Diseases; Muscles; Phosphocreatine; Radiation Injuries, Experimental; Radiation-Protective Agents; Rats