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Results for “PHOSPHOCREATINE”

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PubMed1990

[Synthesis of phosphocreatine in heart mitochondria of rats with hyperthyroidism].

The mechanisms of the phosphocreatine/creatine ratio decrease in female Wistar rats with hyperthyroidism were studied. L-Thyroxin was injected to animals in doses of 50 and 100 micrograms/100 g of body weight, daily for 1 and 2 weeks. Oxidative phosphorylation and the rate of phosphocreatine synthesis were studied in isolated rat heart mitochondria. It was found that hyperthyroidism caused an increase in the ADP-activated mitochondrial respiration, whereas the coupling between electron transport and ADP phosphorylated remained at a constant level. Besides oxidative phosphorylation, activation, hyperthyroidism increased the rate of phosphocreatine synthesis at high values of the phosphocreatine/oxygen ratio. Thus, hyperthyroidism is unaccompanied by and significant changes in the coupling of mitochondrial creatine kinase with oxidative phosphorylation.

Adenosine Diphosphate↗

PubMed1990

Functional coupling of glycolysis and phosphocreatine utilization in anoxic fish muscle. An in vivo 31P NMR study.

Three fish species with different strategies for anoxic survival (goldfish, tilapia, and common carp) were exposed to environmental anoxia (4, 3, and 1 h, respectively). The concentrations of high energy phosphate compounds and inorganic phosphate, besides the intracellular pH in the epaxial muscle were measured during anoxia and recovery by in vivo 31P NMR spectroscopy. The concentration of free ADP was calculated from the equilibrium constant of creatine kinase. During anoxia the patterns of phosphocreatine utilization and tissue acidification are remarkedly similar. Free ADP rises rapidly during the initial period of oxygen deficiency and reaches a plateau in goldfish and tilapia, while it keeps rising in the common carp. At elevated levels of free ADP, the creatine kinase reaction and anaerobic glycolysis are functionally coupled by H+ as a common intermediate. The coupling between both processes disappears upon reoxygenation, when mitochondrial respiration induces a rapid drop of [free ADP]. The removal of ADP shifts the creatine kinase equilibrium toward phosphocreatine synthesis despite the low pH.

Adenosine Diphosphate↗

PubMed1990

[Oxidative damage to the myocardium: the protective action of exogenous phosphocreatine].

Oxidative damage of the isolated perfused rat heart was caused by addition of 90 microM H2O into Krebs-Henseleit solution. After 20 min of H2O2 addition an elevation of diastolic pressure (irreversible contracture) was observed followed by decrease of developed tension and heart work. Addition of phosphocreatine (10 mM) at constant total sodium concentration prevented the development of contracture and diminished the decrease of cardiac work. This protective effect is probably related to the elevation of structural order of phospholipids by phosphocreatine.

Animals↗

PubMed1986

[Possible mechanism of the protective effect of phosphocreatine on the ischemic myocardium].

The uptake of 32P-phosphocreatine by control and ischemic isolated perfused rat hearts has been studied. The rate of phosphocreatine (PCr) uptake by the hearts after 35 minutes of ischemia was two times that in control hearts at 0.5-10 mM PCr in the perfusate. At 10 mM PCr in the perfusate, this rate was 182 nmoles/min/g dry weight. The 5'-nucleotidase and phosphatase activities were found in the crude plasma membrane fraction of rat heart. The pH-dependence of these enzymes was examined. The 5'-nucleotidase activity decreased with a drop in pH from 8.0 to 6.0. The phosphatase activity in the crude plasma membrane fraction of rat heart was increased 2-fold with a decrease in pH from 8.0 to 6.0. The 5'-nucleotidase activity was inhibited by 10 mM PCr in the presence of 5 mM Mg2+. This inhibition was pH-dependent with a maximum (58%) at pH 6.0. The inhibition of phosphatase activity by PCr was independent of pH and reached 20% in the presence of 10 mM PCr. Some feasible mechanisms of the protective effect of PCr on ischemic myocardium are discussed.

5'-Nucleotidase↗

PubMed1988

[Characteristics of the anti-arrhythmia effect of phosphocreatine in the acute stage of experimental myocardial infarction].

Antiarrhythmic and antifibrillatory effects of exogenous phosphocreatine, administered to animals at different dates after the onset of experimental myocardial infarction, were examined. Experiments were carried out on anesthetized dogs with acute one-step coronary artery ligation or in waking dogs 24 to 48 hours after two-step ligation of the descending branch of the left coronary artery (Harris's method). Major cardiac functional and hemodynamic parameters and ECG were recorded. The values obtained, using these models, show that exogenous phosphocreatine possesses high antiarrhythmic and antifibrillatory activities within first hours of coronary occlusion and is less effective after 24 hours of infarction.

Animals↗

PubMed1987

[Phosphocreatine: thrombocyte aggregation in patients with stenocardia].

Phosphocreatine (Neoton produced by "Schapparelli Farmaceutici") was infused intravenously to 27 patients with CHD at a dose of 2000 mg: 13 patients with unstable and 10 patients with stable angina pectoris. Phosphocreatine blocked ADP-induced platelet aggregation in these patients, but had no significant effect on the platelet aggregation induced by collagen, platelet activating factor or serotonin.

Adenosine Diphosphate↗

PubMedDate not supplied

[Phosphocreatine and skeletal musculature: in vivo research].

Phosphocreatine has been shown having significant effects on striated skeletal musculature. In fact, it was shown, by experimental researches, that phosphocreatine interfered with the state of fatigue induced in the Mus musculus and in rats, by the swimming test.

Animals↗

PubMed1993

[Exogenous phosphocreatine in the prevention and treatment of cardiac insufficiency in patients with myocardial infarction].

Central, intracardiac hemodynamics and myocardial contractility were assessed in 97 inpatients with macrofocal myocardial infarction. Of them, 71 received conventional chemotherapy versus 26 patients given additionally intravenous phosphocreatine (neoton). The total dose of neoton 30 g was injected during the course of 6 days following the disease onset. With minimal changes in central hemodynamics, phosphocreatine was found to prevent left-ventricular dilatation and development of congestive heart failure by decreasing preload, to maintain myocardial contractility without reduction.

Adult↗

PubMed1994

The effect of exogenous phosphocreatine on maximal walking distance, blood rheology, platelet aggregation, and fibrinolysis in patients with intermittent claudication.

Thirty-seven men with angiography or ultrasound confirmed peripheral arterial occlusive disease were divided into two groups. Group 1 included 24 patients treated with one daily infusion of 10 g of phosphocreatine in 200 ml of solvent for 10 days. Group 2 included 13 patients who were given 0.9% NaCl in the same scheme. Groups were comparable in: duration of intermittent claudication, maximal walking distance, Ketle index, cholesterol, triglycerides, frequency of ischemic heart disease, hypertension, diabetes, smoking. Patients were examined 4 times: before starting, on second day, after treatment period, and 1 month after. Treadmill-test; ADP-, PAF-, 5-HT-induced platelet aggregation; D-dimer; PAI-1 activity; blood viscosity at high and low shear rate; hematocrit were performed. After treatment maximal walking distance significantly increased in patients of Group 1. Mechanisms of this effects include positive influence of phosphocreatine on platelet aggregation, blood rheology, coagulation and fibrinolytic systems.

Blood Flow Velocity↗

PubMedDate not supplied

[Phosphocreatine metabolic indices during increased and decreased energy expenditures in man].

Changes in phosphocreatine metabolism (creatinine excretion in the urine and arginine content in plasma--one of the amino acids that are involved in creatine synthesis) were studied in 40 male test subjects who performed increased or decreased work and consumed standard protein food. It was shown that there was a correlation between creatinine excretion in the urine and the content of arginine in plasma, on the one hand, and the amount of nitrogen consumed, on the other. It was also found that at increased or decreased energy expenditures creatinine excretion and arginine content elevated. These data are indicative of changes in phosphocreatine metabolism in response to the environmental effects.

Adult↗

PubMed1998

Skeletal muscle phosphocreatine depletion depresses myocellular energy status during sepsis.

OBJECTIVE: To determine the effects of phosphocreatine (PCr) depletion on myocellular energetics. DESIGN: Randomized controlled study. SETTING: University laboratory. MATERIALS: Thirty-eight adult male Wistar rats (110-121 g). METHODS: The poorly metabolized creatine analogue beta-guanidinopropionic acid, (beta-GPA, 2% of a gel diet) was fed to the rats for 14 days to replace (75%) endogenous PCr stores before cecal ligation and puncture (CLP). Rats were randomized to receive sham operation and gel diet (sham-gel group [n=10]), sham operation and beta-GPA diet (sham-beta-GPA group [n=9]), CLP and gel diet (CLP-gel group [n=10]), and CLP and beta-GPA diet (CLP-beta-GPA group [n=9]). On day 14, all animals underwent operation. Twenty-four hours later, in vivo phosphorus 31-labeled magnetic resonance spectroscopy (31P-MRS) of the gastrocnemius muscle was performed. Muscle samples were collected to determine enzyme activities of beta-hydroxyacyl-CoA dehydrogenase, phosphofructokinase, citrate synthase, and the metabolites adenosine triphosphate (ATP), PCr, inorganic phosphate, and creatine. Free adenosine diphosphate levels, the phosphorylation potential, and free energy change of ATP hydrolysis were then calculated. RESULTS: All animals undergoing CLP but no controls had positive results of blood cultures. Although sham-beta-GPA animals had altered bioenergetics, CLP-beta-GPA rats experienced a greater deterioration of energy state compared with CLP-gel controls. Glycolytic and oxidative enzyme activities were not significantly different between groups and therefore could not explain the observed differences. CONCLUSIONS: There is an overall decrease in energy availability during sepsis, which is worsened by PCr depletion. These changes support the contention that PCr plays an important role as an ATP buffer during systemic infection.

Animals↗

PubMed1998

The use of phosphocreatine plus ADP as energy source for motility of membrane-deprived trout spermatozoa.

Live trout spermatozoa initiate flagellar motility for a short period of time (30 s at 18 degrees C), during which their mean beat frequency (BF) decreases steadily from 60 to 20 Hz; motility then stops abruptly. When demembranated, the motility of axonemes lasts much longer, up to 20 min, with high beat frequency, provided that ATP (millimolar concentration) and cAMP (micromolar) are added. In the present paper, the motility of demembranated trout sperm was investigated in the absence of added ATP in various incubation conditions relative to other substrates. Without the addition of exogenous creatine kinase, the addition of phosphocreatine (PCr) and ADP shows the appearance of a progressive activation of all sperm models with BF increasing with time up to high values. Without the addition of cAMP, the BF increases to lower values but flagella propagated poorly coordinated waves for only a few min. Similar progressive activation is also observed when only ADP is added (without any previous in vivo activation) and BF increases up to moderate values. In this latter case, no activation occurs without addition of cAMP. The respective roles of creatine kinase and adenylate kinase in this process were investigated by addition of specific inhibitors such as fluorodinitrobenzene and P1,P5-di(adenosine-5')pentaphosphate in the above described conditions. We conclude from these observations that all the elements necessary for a coupling between ADP/PCr/creatine kinase on one hand and ATP/ADP/dynein on the other appear to be present in trout spermatozoa: thus the existence of a shuttle sustaining this coupling is strongly suggested.

Adenosine Diphosphate↗

PubMed1990

Phosphorus magnetic resonance spectroscopy of patients with mitochondrial cytopathies demonstrates decreased levels of brain phosphocreatine.

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.

Adenosine Triphosphate↗

PubMedDate not supplied

A luminometric method for the determination of ATP and phosphocreatine in single human skeletal muscle fibres.

A sensitive method for the analysis of ATP and phosphocreatine (PCr) in single human skeletal muscle fibres is described. Muscle tissue was freeze-dried and single fibres were dissected free with the aid of low-power microscopy. The fibres were then extracted in trichloroacetic acid and neutralized with KHCO3. The assay is based on the continuous monitoring of light produced as a result of ATP degradation in the firefly luciferase reaction. PCr is measured as the amount of ATP formed in the creatine kinase reaction. The coefficient of variation was less than 4% for both ATP and PCr determination. The amount of tissue required for the assay is approximately 0.5 microgram (dry weight). The assay showed good agreement with spectrophotometric and high-performance liquid chromatographic (HPLC) measurements made upon extracts of whole muscle tissue.

Adenosine Triphosphate↗

PubMed2002

Fast imaging of phosphocreatine in the normal human myocardium using a three-dimensional RARE pulse sequence at 4 Tesla.

PURPOSE: To investigate the use of a three-dimensional rapid acquisition with relaxation enhancement (RARE) pulse sequence for direct acquisition of phosphocreatine (PCr) images of the human myocardium. MATERIALS AND METHODS: A short elliptical birdcage radiofrequency (RF) body coil was constructed to produce a uniform flip angle throughout the chest cavity. In vivo images using a spectrally-selective RARE sequence with a spatial resolution of 1.2 cm x 1.2 cm x 2.5 cm (4 cm(3)) were acquired in nine minutes and 40 seconds. RESULTS: Scans of phantoms demonstrated excellent spectral selectivity. The signal-to-noise ratio in the myocardium ranged from 12.6 in the anterior wall to 5.3 in the mid septum. CONCLUSION: This study demonstrates that PCr data can be acquired using a three-dimensional RARE sequence with greater spatial and temporal resolution than spectroscopic techniques.

Humans↗

PubMed2001

Altered brain phosphocreatine and ATP regulation when mitochondrial creatine kinase is absent.

In cerebral gray matter, ATP concentration is closely maintained despite rapid, large increases in turnover and low substrate reserves. As seen in vivo by (31)P nuclear magnetic resonance (NMR) spectroscopy, brain ATP is stable early in seizures, a state of high energy demand, and in mild hypoxia, a state of substrate deficiency. Like other tissues with high and variable ATP turnover, cerebral gray matter has high phosphocreatine (PCr) concentration and both cytosolic and mitochondrial creatine kinase (UbMi-CK) isoenzymes. To understand the physiology of brain creatine kinases, we used (31)P NMR to study PCr and ATP regulation during seizures and hypoxia in mice with targeted deletion of the UbMi-CK gene. The baseline CK reaction rate constant (k) was higher in mutants than wild-types. During seizures, PCr and ATP decreased in mutants but not in wild-types. The k-value for the CK catalyzed reaction rate increased in wild-types but not in the mutants. Hypoxic mutants and wild-types showed similar PCr losses and stable ATP. During recovery from hypoxia, brain PCr and ATP concentrations returned to baseline in wild-types but were 20% higher than baseline in the mutants. We propose that UbMi-CK couples ATP turnover to the CK catalyzed reaction rate and regulates ATP concentration when synthesis is increased.

Acid Anhydride Hydrolases↗

PubMed1993

Phosphocreatine T1 measurements with and without exchange in the heart.

The intrinsic phosphocreatine (PCr) T1 values measured by time-dependent magnetization transfer in isolated perfused rat, hamster, and turkey hearts were indistinguishable. The value of 3.5 +/- 0.3 s for the rat heart is similar to values measured by other magnetization transfer methods. Irreversibly inhibiting the phosphoryl exchange between PCr and ATP in the rat heart using iodoacetamide changed the apparent T1 values of the two exchanging species when measured by inversion recovery: The apparent T1 of PCr increased from 1.92 +/- 0.06 s to 3.55 +/- 0.06 s, in excellent agreement with the intrinsic T1 measured by magnetization transfer. The apparent T1 of [gamma-P]ATP decreased from 0.92 +/- 0.07 s to 0.44 +/- 0.03 s. The value for the T1 of [gamma-P]ATP in hearts with inhibited phosphoryl exchange was similar to T1 values for [alpha-P]ATP and [beta-P]ATP, which remained unchanged. This illustrates that apparent T1 values for PCr and [gamma-P]ATP measured by inversion recovery in the presence of exchange are average T1 values in between the intrinsic values. The large differences between the intrinsic T1 measured by magnetization transfer and the T1 measured by inversion recovery makes the use of the appropriate value in different applications quantitatively important.

Adenosine Triphosphate↗

PubMed1998

Fast imaging of phosphocreatine using a RARE pulse sequence.

A technique is described for acquiring phosphocreatine (PCr) images of skeletal muscle using a rapid acquisition with relaxation enhancement (RARE) pulse sequence. All of the phosphorus metabolites other than PCr are forced to dephase within the first few echoes, whereas the Carr-Purcell Meiboom-Gill (CPMG) pulse sequence maintains a high PCr signal long enough to acquire 64 echoes in a single shot. Axial PCr images of a human forearm with a signal-to-noise ratio of 9 were acquired in 2 min. The effect of the refocusing pulse section profile on the ratio of desired to undesired metabolite signal is demonstrated.

Forearm↗