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1.
Phosphocreatine in Cardiac Surgery Patients: A Meta-Analysis of Randomized Controlled Trials.
Mingxing, F, Landoni, G, Zangrillo, A, Monaco, F, Lomivorotov, VV, Hui, C, Novikov, M, Nepomniashchikh, V, Fominskiy, E
Journal of cardiothoracic and vascular anesthesia. 2018;(2):762-770
Abstract
OBJECTIVE There is experimental evidence that phosphocreatine (PCr) can decrease ischemia/reperfusion injury of the heart. The authors investigated if PCr would improve heart performance as compared with standard treatment in cardiac surgery. DESIGN Meta-analysis of randomized controlled trials. SETTING Hospitals. PARTICIPANTS Adult and pediatric patients undergoing cardiac surgery. INTERVENTIONS The ability of PCr to improve cardiac outcomes as compared with standard treatment was investigated. MEASUREMENTS AND MAIN RESULTS PubMed/Medline, Embase, Scopus, Cochrane Library, China National Knowledge Infrastructure, WANGFANG DATA, and VIP Paper Check System were searched to March 1 2017. The authors included 26 randomized controlled trials comprising 1,948 patients. Random and fixed-effects models were used to estimate odds ratio (OR) and mean difference (MD) with 95% confidence interval (CI). PCr use was associated with reduced rates of intraoperative inotropic support (27% v 44%; OR 0.47, 95% CI 0.35-0.61; p < 0.001), major arrhythmias (16% v 28%; OR 0.44, 95% CI 0.27-0.69; p < 0.001), as well as increased spontaneous recovery of the cardiac rhythm immediately after aortic declamping (50% v 34%; OR 2.45, 95% CI 1.82-3.30; p < 0.001) as compared with standard treatment. The use of PCr decreased myocardial damage and augmented left ventricular ejection fraction in the postoperative period; however, MD for these outcomes were small and do not seem to be clinically significant. CONCLUSIONS In randomized trials, PCr administration was associated with reduced rates of intraoperative inotropic support and major arrhythmias, and increased spontaneous recovery of the cardiac rhythm after aortic declamping. Large multicenter evidence is needed to validate these findings.
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2.
Creatine Phosphate Administration in Cell Energy Impairment Conditions: A Summary of Past and Present Research.
Gaddi, AV, Galuppo, P, Yang, J
Heart, lung & circulation. 2017;(10):1026-1035
Abstract
BACKGROUND Creatine phosphate (CrP) plays a fundamental physiological role by providing chemical energy for cell viability and activity, especially in muscle tissue. Numerous pathological conditions, caused by acute or chronic ischaemic situations, are related to its deficiency. For these reasons, it has been used as a cardioprotective agent in heart surgery and medical cardiology for many years. OBJECTIVE This article gives a brief overview of the main characteristics of exogenous CrP. METHODS Previous review articles on CrP were screened for relevant information and references. Results from selected studies were reviewed and classified according to the topics in this review article and provided further interesting information on the pharmacological role of this molecule. RESULTS Besides CrP's well known cell energy and function restoring properties, new evidence is emerging regarding its antioxidant and anti-apoptotic properties. Use of CrP is well established clinically as an intraoperative and perioperative adjuvant in heart operations (valve replacement, coronary artery bypass grafting, congenital heart defect repair), and as an additional agent in medical cardiology therapy for acute myocardial infarction and acute and chronic heart failure. In particular, there are promising potential new CrP uses in neurology, such as in cerebral ischaemia and hypoxic ischaemic encephalopathy. CONCLUSIONS This review article describes the role of CrP treatment in cardiological indications, such as cardioprotection in cardioplegia and in myocardiopathies of various etiopathogenesis, as well as in other clinical indications such as skeletal muscle rehabilitation and neurological conditions.
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3.
Role of Exogenous Phosphocreatine in Chemotherapy-induced Cardiomyopathy.
Parve, S, Aliakberova, GI, Gylmanov, AA, Abdulganieva, DI
Reviews in cardiovascular medicine. 2017;(2):82-87
Abstract
The 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) regimen is widely used in the management of breast cancer. The common cardiotoxic effects of doxorubicin include congestive heart failure and left ventricular dysfunction, and those of cyclophosphamide include pericarditis, myocarditis, and congestive heart failure. It has been postulated that cardiotoxicity of 5-fluorouracil presents as coronary artery diseases (eg, angina). Cardiomyopathy is a common outcome following treatment with the FAC regimen. We report on a 52-year-old woman with cardiomyopathy following chemotherapy and radiation therapy. The patient did not respond well to b-blockers and angiotensin-converting enzyme inhibitors. After the addition of exogenous phosphocreatine, the patient's cardiac condition improved significantly.
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4.
Cardiac protection with phosphocreatine: a meta-analysis.
Landoni, G, Zangrillo, A, Lomivorotov, VV, Likhvantsev, V, Ma, J, De Simone, F, Fominskiy, E
Interactive cardiovascular and thoracic surgery. 2016;(4):637-46
Abstract
Phosphocreatine (PCr) plays an important role in the energy metabolism of the heart and a decrease in its intracellular concentration results in alteration of myocardium energetics and work. We conducted a meta-analysis of all randomized and matched trials that compared PCr with placebo or standard treatment in patients with coronary artery disease or chronic heart failure or in those undergoing cardiac surgery. We systematically searched PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials and Google Scholar up to 1 November 2015, for pertinent trials. The primary outcome was all-cause mortality. Secondary outcomes included inotrope use, ejection fraction (EF), peak creatinine kinase-myocardial band (CK-MB) release and the incidence of major arrhythmias, as well as spontaneous recovery of the heart performance in the subgroup of patients undergoing cardiac surgery with cardiopulmonary bypass. We pooled odds ratio (OR) and mean difference (MD) using fixed- and random effects models. We identified 41 controlled trials, of them 32 were randomized. Patients receiving PCr had lower all-cause mortality when compared with the control group [61/1731 (3.5%) vs 177/1667 (10.6%); OR: 0.71, 95% CI: 0.51-0.99; P = 0.04; I(2) = 0%; with 3400 patients and 22 trials included]. Phosphocreatine administration was associated with higher LVEF (MD: 3.82, 95% CI: 1.18-6.46; P = 0.005; I(2) = 98%), lower peak CK-MB release (MD: -6.08, 95% CI: -8.01, -4.15; P < 0.001; I(2) = 97%), lower rate of major arrhythmias (OR: 0.42; 95% CI: 0.27-0.66; P < 0.001; I(2) = 0%), lower incidence of inotropic support (OR: 0.39, 95% CI: 0.25-0.61; P < 0.001; I(2) = 56%) and a higher level of spontaneous recovery of the heart performance after cardiopulmonary bypass (OR: 3.49, 95% CI: 2.28-5.35; P < 0.001; I(2) = 49%) when compared with the control group. In a mixed population of patients with coronary artery disease, chronic heart failure or in those undergoing cardiac surgery, PCr may reduce all-cause short-term mortality. In addition, PCr administration was associated with improved cardiac outcomes. Owing to the pharmacological plausibility of this effect and to the concordance of the beneficial effects of PCr on several secondary but important outcomes and survival, there is urgent need for a large multicentre randomized trial to confirm these findings.
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5.
Muscle energetics during explosive activities and potential effects of nutrition and training.
Sahlin, K
Sports medicine (Auckland, N.Z.). 2014;(Suppl 2):S167-73
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Abstract
The high-energy demand during high-intensity exercise (HIE) necessitates that anaerobic processes cover an extensive part of the adenosine triphosphate (ATP) requirement. Anaerobic energy release results in depletion of phosphocreatine (PCr) and accumulation of lactic acid, which set an upper limit of anaerobic ATP production and thus HIE performance. This report focuses on the effects of training and ergogenic supplements on muscle energetics and HIE performance. Anaerobic capacity (i.e. the amount of ATP that can be produced) is determined by the muscle content of PCr, the buffer capacity and the volume of the contracting muscle mass. HIE training can increase buffer capacity and the contracting muscle mass but has no effect on the concentration of PCr. Dietary supplementation with creatine (Cr), bicarbonate, or beta-alanine has a documented ergogenic effect. Dietary supplementation with Cr increases muscle Cr and PCr and enhances performance, especially during repeated short periods of HIE. The ergogenic effect of Cr is related to an increase in temporal and spatial buffering of ATP and to increased muscle buffer capacity. Bicarbonate loading increases extracellular buffering and can improve performance during HIE by facilitating lactic acid removal from the contracting muscle. Supplementation with beta-alanine increases the content of muscle carnosine, which is an endogenous intracellular buffer. It is clear that performance during HIE can be improved by interventions that increase the capacity of anaerobic ATP production, suggesting that energetic constraints set a limit for performance during HIE.
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Role of the phosphocreatine system on energetic homeostasis in skeletal and cardiac muscles.
GuimarĂ£es-Ferreira, L
Einstein (Sao Paulo, Brazil). 2014;(1):126-31
Abstract
Adenosine triphosphate is the present energy currency in the body, and is used in various cellular and indispensable processes for the maintenance of cell homeostasis. The regeneration mechanisms of adenosine triphosphate, from the product of its hydrolysis - adenosine diphosphate - are therefore necessary. Phosphocreatine is known as its quickest form of regeneration, by means of the enzyme creatine kinase. Thus, the primary function of this system is to act as a temporal energy buffer. Nevertheless, over the years, several other functions were attributed to phosphocreatine. This occurs as various isoforms of creatine kinase isoforms have been identified with a distinct subcellular location and functionally coupled with the sites that generate and use energy, in the mitochondria and cytosol, respectively. The present study discussed the central and complex role that the phosphocreatine system performs in energy homeostasis in muscle cells, as well as its alterations in pathological conditions.
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High-energy phosphate metabolism in the exercising muscle of patients with peripheral arterial disease.
Schocke, M, Esterhammer, R, Greiner, A
VASA. Zeitschrift fur Gefasskrankheiten. 2008;(3):199-210
Abstract
Patients with peripheral arterial disease (PAD) suffer from impaired muscle function due to insufficient oxygen supply during exercise, mitochondrial damages, unfavourable muscle fibre type distribution and impaired exercise tolerance. These factors influence the symptoms as well as the quality of life in PAD patients and are closely connected to failures of high-energy phosphate metabolism. At onset of muscle exercise, the mitochondrial capacity cannot match the increased demand. The oxygen supply via blood flow must be increased. Meanwhile, anaerobic glycolysis and internal stores of oxygen like mixed venous blood and myoglobin as well as internal stores of high-energy phosphates like phosphocreatine (PCr) are adducted for the provision of additional adenosine-triphosphate (ATP), which is consumed by the ATPase at the myofibrils in order to fuel muscle contraction. Since the ATP production is insufficient, this phase (anaerobic phase) is characterized by a progressive decrease in PCr, which can be accurately measured by phosphorus 31 magnetic resonance spectroscopy (31p MRS). If the oxygen supply is improved, the mitochondrial capacity can match the increased metabolic demand. This phase is the aerobic phase, which is indicated by a steady-state of PCr hydrolysis. In PAD patients or experimental models of peripheral ischemia, the anaerobic phase is prolonged or does not pass into the aerobic phase resulting in exercise abortion. This review summarizes the results of 31p MRS studies investigating the high-energy phosphate metabolism during ischemic exercise in healthy humans and during ramp or incremental exercise in PAD patients.
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Absolute quantification of phosphorus metabolite concentrations in human muscle in vivo by 31P MRS: a quantitative review.
Kemp, GJ, Meyerspeer, M, Moser, E
NMR in biomedicine. 2007;(6):555-65
Abstract
31P MRS offers a unique view of muscle metabolism in vivo, but correct quantification is important. Inter-study correlation of estimates of [Pi] and [phosphocreatine (PCr)] in a number of published studies suggest that the main technical problem in calibrated 31P MRS studies is the measurement of PCr and Pi signal intensities, rather than absolute quantification of [ATP]. For comparison, we discuss the few published biopsy studies of calf muscle and a selection of the many studies of quadriceps muscle. The ATP concentration is close to the value that we obtained in calf muscle in our own study, presented here, on four healthy subjects, by localised 31P MRS using a surface coil incorporating an internal reference and calibrated using an external phantom. However, the freeze-clamp biopsy PCr concentration is approximately 20% lower than the value obtained by 31P MRS, consistent with PCr breakdown by creatine kinase during freezing. Finally, we illustrate some consequences of uncertainty in resting [PCr] for analysis of mitochondrial function from PCr kinetics using a published 31P MRS study of exercise and recovery: the lower the assumed resting [PCr], the lower the absolute rate of oxidative ATP synthesis estimated from the PCr resynthesis rate; in addition, the lower the assumed resting [PCr], or the higher the assumed [total creatine], the higher the apparent resting [ADP], and therefore the more sigmoid the relationship between the rate of oxidative ATP synthesis and [ADP]. Correct quantification of resting metabolite concentrations is crucially important for this sort of analysis. Our own results ([PCr] = 33 +/- 2 mM, [Pi] = 4.5 +/- 0.2 mM, and [ATP] = 8.2 +/- 0.4 mM; mean +/- SEM) are close to the overall mean values of the 10 published studies on calf muscle by 'calibrated' 31P MRS (as in the present work), and of [PCr] and [Pi] in a representative selection of 'uncalibrated' 31P MRS studies (i.e. from measured PCr/ATP and Pi/ATP ratios, assuming a literature value for [ATP]).
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9.
Metabolic response and fatigue in soccer.
Bangsbo, J, Iaia, FM, Krustrup, P
International journal of sports physiology and performance. 2007;(2):111-27
Abstract
The physical demands in soccer have been studied intensively, and the aim of the present review is to provide an overview of metabolic changes during a game and their relation to the development of fatigue. Heart-rate and body-temperature measurements suggest that for elite soccer players the average oxygen uptake during a match is around 70% of maximum oxygen uptake (VO2max). A top-class player has 150 to 250 brief intense actions during a game, indicating that the rates of creatine-phosphate (CP) utilization and glycolysis are frequently high during a game, which is supported by findings of reduced muscle CP levels and severalfold increases in blood and muscle lactate concentrations. Likewise, muscle pH is lowered and muscle inosine monophosphate (IMP) elevated during a soccer game. Fatigue appears to occur temporarily during a game, but it is not likely to be caused by elevated muscle lactate, lowered muscle pH, or change in muscle-energy status. It is unclear what causes the transient reduced ability of players to perform maximally. Muscle glycogen is reduced by 40% to 90% during a game and is probably the most important substrate for energy production, and fatigue toward the end of a game might be related to depletion of glycogen in some muscle fibers. Blood glucose and catecholamines are elevated and insulin lowered during a game. The blood free-fatty-acid levels increase progressively during a game, probably reflecting an increasing fat oxidation compensating for the lowering of muscle glycogen. Thus, elite soccer players have high aerobic requirements throughout a game and extensive anaerobic demands during periods of a match leading to major metabolic changes, which might contribute to the observed development of fatigue during and toward the end of a game.
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Investigations of back muscle fatigue by simultaneous 31P MRS and surface EMG measurements.
Rzanny, R, Grassme, R, Reichenbach, JR, Scholle, HC, Kaiser, WA
Biomedizinische Technik. Biomedical engineering. 2006;(5-6):305-13
Abstract
Investigations of back muscle fatigue are important for understanding the role of muscle strain in the development of low back pain. The aim of this contribution is to review the two main techniques used for in vivo investigations of metabolic and electrophysiological changes, namely magnetic resonance phosphorous spectroscopy ((31)P MRS) and surface electromyography (SEMG), and to report some of our recent results on simultaneous measurements using these techniques during isometric back-muscle contraction in volunteers. Since it appears that electrophysiological and metabolic factors are simultaneously involved in the processes of fatigue and muscle recovery during load application, simultaneous acquisition of complete information is quite promising for obtaining new insights into the metabolic origin of electrophysiological changes or vice versa. Performing these measurements simultaneously, however, is more intricate owing to the occurrence of signal artifacts caused by mutual signal interferences of both techniques. Besides these mutual disturbances, further experimental difficulties are related to spatial limitations within the bore of clinical whole-body high-field magnetic resonance (MR) systems (1.5 T) and the sensitivity of MR measurements to motion-induced artifacts. Our own experimental results are presented, and problems that occur using both techniques simultaneously, as well as possibilities to resolve them, are discussed. The results shed light on the interrelation of electrophysiological and metabolic changes during fatigue of the back muscle while performing an exercise.