SEARCH · PubMed Health

Results for “PHOSPHOCREATINE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources

PubMed1992

Determination of free creatine and phosphocreatine concentrations in the isolated perfused rat heart by 1H- and 31P-NMR.

To measure free creatine in the isolated perfused rat heart, the concentration of phosphocreatine, and phosphocreatine plus creatine (sigma Cr) were measured by 31P- and 1H-NMR, respectively. Quantification was performed in the presence and absence of an intraventricular balloon filled with a known amount of PCr, which acted as an external standard. Total (free plus bound) phosphocreatine and creatine were measured by HPLC analysis of extracts from the same hearts, freeze-clamped at the end of the perfusions. A greater concentration of creatine (mumol/g dry wt.) in the perfused rat heart was measured by HPLC analysis (40.3 +/- 2.38 (11)) as compared to NMR (34.6 +/- 1.95 (11)), whilst no significant difference was observed in the measurement of phosphocreatine between the two assay methods. Consequently, a greater sigma Cr was measured by HPLC. This work suggests that the majority of Cr in the heart is NMR visible and unbound, so available to interact with creatine kinase. The lower free ADP concentration calculated from NMR measurements (53.3 +/- 3.80 microM (9)) was not significantly different from that determined by HPLC analysis (56.9 +/- 5.90 microM (9)). This suggests that the concentration of free ADP in the heart is higher than values where it can regulate oxidative phosphorylation most effectively.

Animals↗

PubMed1976

Occurrence of free creatine, phosphocreatine and creatine phosphokinase in adipose tissue.

We evaluated brown and white adipose tissues for the presence of creatine, phosphocreatine and creatine phosphokinase activity. In rats 3.6 and 0.4 mumol of total creatine were found per g wet weight of brown and white adipose tissues, respectively. We were able to identify creatine by thin-layer chromatography after a pulse label of [14C]creatine had been given in vivo. Free creatine and phosphocreatine were shown to occur by column chromatography. Of the total creatine of brown adipose tissue, approximately one third to one half were attributable to phosphocreatine. The activity of creatine phosphokinase was demonstrated in both white and brown adipose tissue, the values of the latter prevailing over those of the former by a factor of 200, if based on wet weight, or 50, if expressed as specific enzyme activity. The labeling of total creatine in vivo proceeded much faster in adipose tissue than in skeletal muscle. The results strongly suggest that the energy metabolism of adipose tissue is closely dependent on the presence of creatine. The specific activities of free creatine and phosphocreatine of brown adipose tissue differed strikingly as long as 24 h after radioactive creatine was injected; this difference points to a metabolic or structural compartmentation of creatine.

Adipose Tissue↗

PubMed2002

Hypoxia-induced lipid peroxidation in rat brain and protective effect of carnitine and phosphocreatine.

The exposure to hypobaric hypoxia increased lipid peroxidation as indicated by thiobarbituric acid-reactive substances [TBARS] in rat brain. Plasma lactate/pyruvate ratio was used as a marker of hypoxia. We compared the protective effect of alpha-tocopherol with the effect of L-carnitine or phosphocreatine. Rats pretreated with alpha-tocopherol, L-carnitine, or phosphocreatine had lower TBARS levels after the exposure to hypobaric hypoxia. However, lactate/ pyruvate ratio was improved only in rats pretreated with L-carnitine or phosphocreatine. We conclude from our data that, contrary to alpha-tocopherol, protective effects of L-carnitine and phosphocreatine administrations are due to their regulation of metabolic reactions during hypobaric hypoxia rather than to their scavenger activity.

Animals↗

PubMed2001

Effects of phosphocreatine on apoptosis in a cell-free system.

The characteristic morphological and biochemical changes during caspase-mediated apoptosis can be reproduced to a large extent in a Xenopus laevis egg extract cell-free system by addition of mouse liver nuclei and exogenous cytochrome c. We show that in this system phosphocreatine accelerated the apoptotic morphological changes of the nuclei, but selectively inhibited DNA fragmentation. Western blot showed that the degradation of lamins A and C is accelerated, which is possibly responsible for the nuclear changes during cell apoptosis. However, the degradation of ICAD/DFF45-like protein in the egg extracts is inhibited in a time-dependent manner. Exogenous creatine, ATP, and several organic acids have no effect on DNA fragmentation, excluding the possibility that creatine, ATP, or acidic conditions resulting from phosphocreatine are responsible for inhibiting DNA fragmentation. Lithium chloride, a kinase inhibitor, can overcome the phosphocreatine effects and can restore DNA fragmentation. Our results indicate that phosphocreatine protects ICAD/DFF45-like protein from proteolysis, probably through kinase actions, resulting in its resistance to caspase cleavage and leading to an inhibition of DNA fragmentation.

Adenosine Triphosphate↗

PubMed1993

Measurement of phosphocreatine in cutaneous tissue by high pressure liquid chromatography.

A high pressure liquid chromatography technique for measuring phosphocreatine and adenine nucleotides in human cutaneous tissue is described. The presence of phosphocreatine in human skin was confirmed by this analytic method. Molar concentration of phosphocreatine and adenine nucleotides were determined in normal skin and in benign and malignant skin lesions. The preliminary results suggest that absolute amounts of phosphocreatine and adenine nucleotides and phosphocreatine/adenosine triphosphate ratios in malignant skin neoplasms and benign cutaneous lesions are different from those measured in normal nonischemic human skin.

Adenine Nucleotides↗

PubMed1993

31P NMR relaxation does not affect the quantitation of changes in phosphocreatine, inorganic phosphate, and ATP measured in vivo during complete ischemia in swine brain.

Ischemia-induced changes in 31P NMR relaxation were examined in 16 piglets. NMR spectra were acquired under control conditions and during complete cerebral ischemia induced via cardiac arrest. Changes in T1 were assessed directly in six animals during control conditions and after 30-45 min of complete ischemia when changes in brain Pi levels had reached a plateau. The T1 for Pi did not change, i.e., 2.3 +/- 0.5 s during control conditions versus 2.4 +/- 1.0 s during ischemia. To evaluate phosphocreatine and ATP, two types of spectra, with a long (25-s) or short (1-s) interpulse delay time, were collected during the first 10 min of ischemia (n = 10). Both types of spectra showed the same time course of changes in phosphocreatine and ATP levels, implying that the T1 relaxation times do not change during ischemia. There were no changes in the linewidths of phosphocreatine, ATP, or Pi during ischemia, implying that the T2* values remain constant. Our results suggest that the 31P T1 and T2* for phosphocreatine, Pi, and ATP do not change during ischemia, and therefore changes in 31P NMR peak intensity accurately reflect changes in metabolite concentrations.

Adenosine Triphosphate↗

PubMed1979

Phosphocreatine does not inhibit rabbit muscle phosphofructokinase or pyruvate kinase.

Certain phosphocreatine preparations contain a contaminant that inhibits phosphofructokinase and pyruvate kinase assays. The contaminant can be separated from phosphocreatine by anion exchange chromatography. After appropriate purification, phosphocreatine has no effect on phosphofructokinase or pyruvate kinase; thus, there is no evidence that it serves muscle as a regulator of these enzymes. Although the inhibitory preparations of phosphocreatine contain inorganic phosphate and trace amounts of more negatively charged phosphorylated contaminants, the inhibitor is not inorganic phosphate or pyrophosphate. The nature of the inhibitor remains to be determined.

Animals↗

PubMed1991

[Phosphocreatine, tocopheryl phosphate and their combination in acute ischemia and myocardial reperfusion in dogs: the effect on rhythm disorders, left ventricle contractility and infarct size].

The effects of phosphocreatine and tocopheryl phosphate and their combined use in ischemia and reperfusion of the heart were studied in anesthetized dogs. The investigation focused on the size of myocardial infarction and left ventricular contractility, ischemic and reperfusion arrhythmias were assessed using Holter monitoring. Phosphocreatine was found to reduce the number of arrhythmias and to prevent the fatal outcomes in myocardial ischemia animals but not to influence the reperfusion rhythm disturbances. Combined administration of tocopheryl phosphate and phosphocreatine, in contrast to their isolated use, completely prevented the development of ventricular fibrillations and fatal outcomes in the animals with reconstructed coronary flow. Administration of phosphocreatine restricted the infarction size, combined use of the drugs facilitated its further reduction, while the group with isolated administration of tocopheryl phosphate showed the infarction size to differ insignificantly from the control values. Combined administration of the drugs, unlike their use alone, improved left ventricular contractility in reperfusion of ischemic myocardium. The cardioprotective effect observed in combined administration of the drugs was attended with depressed lipid peroxidation in reperfused myocardium.

Animals↗

PubMed1990

[Phosphocreatine in the treatment of patients with myocardial infarct: effects on hemodynamics and oxygen supply].

Changes in the major parameters of central and intracardiac hemodynamics and body's oxygen supply were examined in 93 patients with massive myocardial infarction in the in-hospital period of the disease. Traditional therapy was given to 71 patients; in addition, phosphocreatine infusions (a course dose being 30 g) were used in 22 patients in acute myocardial infarction. Phosphocreatine therapy failed to substantially affect cardiac pump function, but prevented left ventricular dilation and development of congestive heart failure. The patients receiving phosphocreatine showed an increase in body's oxygen consumption due to its elevated tissue extraction. No adverse effects of phosphocreatine were found.

Adult↗

PubMed1988

[Effect of exogenous phosphocreatine on the size of experimental myocardial infarction].

The purpose of the study was to investigate the effect of exogenous phosphocreatine on the infarction size in experimental occlusion of a coronary artery. Experiments were carried out in anesthetized cats, in which the descending branch of the left coronary artery was ligated. Damaged zone was visualized by intravenous administration of fluorescent Thioflavin T dye. Tissue samples were taken from the heart 3, 6 and 72 hours after the ligation. Exogenous phosphocreatine was administered as a bolus injection (200 mg/kg body weight) 5 minutes before the ligation and was followed by continuous infusion for 3-6 hours at the rate of 5 mg/min/kg body weight. Administration of exogenous phosphocreatine remarkably decreased the size of severe and relative ischemia (by 37% and 71%, respectively, after 3 hours, and by 59% and 86%, respectively, after 6 hours). The size of the necrotic zone, determined after 72 hours, was decreased by 63% in the phosphocreatine experiments.

Animals↗

PubMed1987

Augmentation of experimental skin flap survival via postoperative phosphocreatine replacement.

Despite improvements in our understanding of cutaneous vascular territories, clinical skin flap necrosis resulting from ischemic compromise is still a reality. Therapy with vasodilators has been generally unsuccessful, but replacement of high-energy phosphometabolites through the use of ATP-MgCl2 and fructose 1,6-diphosphate has been effective. Recently we reported that phosphocreatine is the major high-energy phosphometabolite in mammalian skin and that ATP levels and cellular well-being in skin flaps are dependent on adequate supply of this phosphometabolite. We report herein the successful augmentation of survival of ischemically compromised skin flaps through postoperative phosphocreatine infusion. This metabolite effectively circumvents the nonfunctioning mitochondrial creatine-phosphocreatine energy shuttle without disturbing the delicate [ATP]/[ADP] balance in the cytosol. In addition, phosphocreatine may favorably redistribute blood flow from muscle to the ischemically compromised skin.

Animals↗

PubMed1985

[Mechanism of the anti-arrhythmic action of phosphocreatine in acute myocardial ischemia].

The association between phosphocreatine's antifibrillatory action and its effect on the excitement propagation processes in the ischemic area was investigated under acute coronary arterial occlusion in dogs. Ischemia considerably reduced the amplitude, and increased the duration and time of onset, in local electrograms, and provoked cardiac fibrillation at the time of occlusion or during the recovery of coronary flow. A single intravenous injection of 300 mg/kg phosphocreatine eliminated cardiac fibrillation and largely prevented electrographic changes in the ischemized area. Phosphocreatinine, phosphocreatine's structural analogue, produced a similar effect. It is suggested that antiarrhythmic action of phosphocreatine and phosphocreatinine is mediated by their membrane effects.

Acute Disease↗

PubMed2001

Quantitative (31)P spectroscopic imaging of human brain at 4 Tesla: assessment of gray and white matter differences of phosphocreatine and ATP.

This report describes the implementation and application of a multicompartment analysis of (31)P spectroscopic imaging data to determine the tissue-specific heterogeneities in metabolite content in the human brain and surrounding tissue. Using this information and a multicompartment regression analysis the phosphocreatine and ATP content of "pure" cerebral gray and white matter, the cerebellum, and skeletal muscle was determined in a group of 10 healthy volunteers. The data were converted to mM units using previously reported values for the T(1)s of phosphocreatine and ATP at 4 T, the water content of human brain, and an external reference for absolute quantification. The phosphocreatine concentration in cerebral gray and white matter, the cerebellum, and skeletal muscle was 3.53 +/- 0.33, 3.33 +/- 0.37, 3.75 +/- 0.66, and 25.8 +/- 2.3 mM, respectively. The ATP concentration in cerebral gray and white matter, the cerebellum, and skeletal muscle was 2.19 +/- 0.33, 3.41 +/- 0.33, 1.75 +/- 0.58, and 8.5 +/- 1.9 mM, respectively. Magn Reson Med 45:46-52, 2001.

Adenosine Triphosphate↗

PubMed1988

Alterations in relative phosphocreatine concentrations in preclinical mouse muscular dystrophy revealed by in vivo NMR.

Using in vivo 31P NMR spectroscopy, the early postnatal development of lower hindleg muscles of normal and dystrophic mice was investigated. Ratios of phosphocreatine and inorganic phosphate, and of phosphocreatine and ATP increased exponentially during normal postnatal growth and differentiation. In dystrophic skeletal muscles, however, the ratios were already considerably lower during the early postnatal period, before histopathological features were observed. The ratios remained lower, relative to normal muscles, at least into the young adult stage. A deficiency in the sequestering of creatine or a defect in the phosphocreatine shuttle is proposed to explain the pathological features observed in this disorder.

Animals↗

PubMed2002

Role of creatine and phosphocreatine in neuronal protection from anoxic and ischemic damage.

Phosphocreatine can to some extent compensate for the lack of ATP synthesis that is caused in the brain by deprivation of oxygen or glucose. Treatment of in vitro rat hippocampal slices with creatine increases the neuronal store of phosphocreatine. In this way it increases the resistance of the tissue to anoxic or ischemic damage. In in vitro brain slices pretreatment with creatine delays anoxic depolarization (AD) and prevents the irreversible loss of evoked potentials that is caused by transient anoxia, although it seems so far not to be active against milder, not AD-mediated, damage. Although creatine crosses poorly the blood-brain barrier, its administration in vivo at high doses through the intracerebroventricular or the intraperitoneal way causes an increase of cerebral phosphocreatine that has been shown to be of therapeutic value in vitro. Accordingly, preliminary data show that creatine pretreatment decreases ischemic damage in vivo.

Adenosine Triphosphate↗

PubMed1988

Reduction of ventricular arrhythmias by phosphocreatine (Neoton) in patients with acute myocardial infarction.

On the basis of the positive results of recent experimental research, a clinical trial of phosphocreatine (Neoton) was carried out in 60 randomized patients with acute myocardial infarction (30 patients in the Neoton group and 30 patients in the control group). Neoton was given intravenously not later than 6 hours after the onset of symptoms, in a dose of 2 gm as a bolus injection, followed by a 2-hour infusion at the rate of 4 gm/hr. Holter monitoring for 24 hours showed a significant decrease in the frequency of ventricular premature beats: in the Neoton-treated group the total number of ventricular premature beats for 24 hours was 690 +/- 179 vs 2468 +/- 737 in the control group (p less than 0.02). During this period of time the number of ventricular tachycardia paroxysms was 6 +/- 2 in the treated group and 97 +/- 35 in the control group (p less than 0.01). No side effects or complications were found after administration of phosphocreatine. It is concluded that phosphocreatine may be a potentially important antiarrhythmic drug for treatment of patients with acute myocardial infarction.

Adult↗

PubMed1983

Synthesis of phosphocreatine and phosphoarginine by mitochondria from various sources.

Mitochondria from heart, skeletal muscle and the liver of the rat have been shown to synthesise phosphoarginine through ATP if supplied with arginine and lobster arginine kinase. Liver mitochondria have been shown to synthesise phosphocreatine through ATP with the aid of the cytosolic isomer of creatine kinase. Mitochondria prepared from muscles of a crustacean, a fish and a bird have been shown oxidatively to synthesise phosphocreatine (crustacean) and phosphoarginine (fish and bird) provided they are supplied with the appropriate kinase and catalytic amounts of ATP. Within one second of the addition of either cytosolic kinases, mitochondria from skeletal muscle and liver begin a steady state synthesis of phosphoarginine or phosphocreatine. The results suggest that, with respect to phosphagen synthesis, the addition of the cytosolic enzymes can substitute for the mitochondrial enzyme. It is difficult therefore to accept a special vectorial function for the bound mitochondrial enzyme at the biological concentrations of ATP and the cytosolic enzymes normally associated with phosphagen synthesis.

Animals↗

PubMed2000

Increase of cerebral phosphocreatine in normal rats after intracerebroventricular administration of creatine.

Intracerebroventricular (ICV) administration of creatine increased cerebral phosphocreatine in normal rats by 67%, the highest increase so far reported in an in vivo model. We used osmotic minipumps (Alzet, Palo Alto, CA, USA) to administer creatine, 0.5 mM, to the lateral ventricle at the rate of 10 microl/h for 3 days. Brain phosphocreatine in saline-treated controls was 33 +/- 17 microM/g protein (mean +/- SD, N = 9). In creatine-treated rats (0.5 mM for 3 days) such content was 55 +/- 17 microM/g protein (mean +/- SD, N = 7). This difference is statistically significant (p = 0.02, t-test). The increase we found in cerebral phosphocreatine is of an order of magnitude comparable to the increase previously found in in vitro experiments, and may be effective in protecting brain tissue from ischemic damage.

Animals↗