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This study aimed to investigate the myocardial protective effect of liquid sodium phosphocreatine cardiac arrest in extracorporeal circulation surgery treating infants with atrial septal defects.Eighty-four infants with atrial septal defects who required extracorporeal circulation surgery treatment at our hospital from January 2016 to June 2018 were divided into an observation group and a control group through a digitally randomized method, with 42 cases in each group. The control group adopted the conventional modified St Thomas II high potassium cold liquid crystal cardiac arrest, while the observation group adopted the liquid sodium phosphocreatine cardiac arrest.The myocardial enzyme indexes of the 2 groups 3, 6, 12, and 24 hours postoperatively were higher than before establishing the cardiopulmonary bypass and the enzyme indexes of the control group at the same time were higher than that of the observation group; adenosine triphosphate, adenosine diphosphate, and other energy levels and the postoperative recovery rate energy levels of the observation group were higher than those in the control group, the difference was statistically significant (P < .05).Liquid sodium phosphocreatine cardiac arrest used in extracorporeal circulation surgery treating infants with atrial septal defects can reduce myocardial ischemia-reperfusion injury, maintain energy supply during ischemia, strengthen the St Thomas II effect, and aid postoperative cardiac function recovery of high potassium cold liquid crystal cardiac arrest used in infants with atrial septal defects and treated with extracorporeal circulation surgery.

Objective: This study aimed to compare the efficacy and safety of ulinastatin combined with creatine phosphate sodium and ribavirin combined with creatine phosphate sodium in the treatment of pediatric viral myocarditis., Patients and Methods: 155 children with viral myocarditis in the Xuzhou Children's Hospital, were retrospectively analyzed. 80 of them received ulinastatin combined with creatine phosphate sodium, and were regarded as observation group; other 75 patients received ribavirin combined with creatine phosphate sodium and were regarded as the control group. The therapeutic efficacy of the two groups was observed, the improved condition of myocardial enzyme indicator and myocardial troponin I (cTn I) in the two groups were compared before and after the treatment., Results: The total effective rates of the patients in the observation group and the control group were 93.75% and 76.00%, respectively. The clinical efficacy of the observation group was better than that of the control group (p<0.05). The electrocardiogram improvement condition of the observation group was better than that of the control group (p<0.05); after the treatment, the expression levels of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), Creatine Kinase (CK-MB), and cTn I in the observation group were (313.37±9.42) U/L, (29.38±4.97) U/L, (23.67±2.89) U/L, (0.12±0.02) μg/L, respectively. The expression levels of LDH, AST, CK-MB, and cTn I in the control group were (322.43±12.32) U/L, (33.43±5.14) U/L, (26.22±3.37) U/L, (0.24±0.04) μg/L. The levels of myocardial enzyme and cTn I in the observation group and the control group after the treatment were lower than that before the treatment (p<0.05), while the level of myocardial enzyme and cTn I in the observation group after the treatment was significantly lower than that in the control group (p<0.05)., Conclusions: The results indicated that, compared with ribavirin combined with creatine phosphate sodium, ulinastatin combined with creatine phosphate sodium had better clinical efficacy in the treatment of pediatric viral myocarditis. It could significantly improve the level of myocardial enzyme indicator and cTn I, and had certain clinical and promotional values and application values.

Background: Major depressive disorder (MDD) is a common psychiatric disorder. With systematic antidepressant treatment, 50-75% of patients have a treatment response but require 4-6 weeks to have their symptoms alleviated. Therefore, researchers anticipate the development of novel fast-acting antidepressants. Previous studies have revealed that the decrease of bio-energetic metabolism may contribute to the occurrence of depression, while our team has found adenosine triphosphate (ATP) and phosphocreatine (PCr) to be fast-acting antidepressants in the depressed-animal model. ATP and PCr have already been widely prescribed clinically as energy supplements for cells. This will be the first clinical attempt of the intravenous administration of ATP and PCr combined with orally administered fluoxetine in MDD., Methods: This is a single-center, randomized, double-blind, placebo-controlled pilot study. A total of 42 patients will be divided randomly into three groups. Patients will receive an intravenous administration of ATP or PCr or saline twice daily combined with orally administered fluoxetine (20 mg/day) for the first 2 weeks and fluoxetine monotherapy for the following 4 weeks. Follow-up assessment will be completed at week 10. Feasibility outcomes will include percentages of patient eligibility, intention to use medication, willingness to participate, drug adherence, completion of the scheduled assessment, retention, drop-out, etc. Physical examination results, Side Effect Rating Scale, adverse events, results from blood tests, electroencephalogram, and electrocardiograph will be recorded for safety evaluation of the augmentation therapy. The trends of efficacy will be evaluated by the reduction rate of the Hamilton Depression Rating Scale, the mean change of the Clinical Global Impression Scale, and the Patients Health Questionaire-9 items., Discussion: In our study, ATP and PCr will be given by intravenous infusion. Thus patients will be hospitalized for the initial 2 weeks for safety concern. Hospitalization will be an impact factor for the recruitment, participation, drop-out, efficacy, results, etc. The evaluation of our feasibility outcomes, study setting, safety of augmentation therapy and possible efficacy trends among groups, will facilitate a full-scale trial design and sample size calculation., Trial Registration: NCT03138681 . Registered on 3 May 2017. First patient: 4 May 2017.

The present study was designed to further explore the role and the underlying molecular mechanism of phosphocreatine (PCr) for cardiac fibrosis in vivo . Isoproterenol (ISO) was used to induce cardiac fibrosis in rats. PCr administration ameliorated fibrosis by reducing collagen accumulation and fibrosis-related signals, including transforming growth factor beta 1 (TGF- β 1), alpha smooth muscle actin ( α -SMA), collagen type I, and collagen type III. Mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF- κ B) signaling pathways, including p38, extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p65, were highly activated by ISO and blocked by PCr. Moreover, PCr decreased ISO-induced matrix metalloproteinase-9 (MMP-9) and increased the tissue inhibitor of metalloproteinase-1 (TIMP-1) expression. Furthermore, PCr suppressed cardiomyocyte apoptosis induced by ISO, as shown by downregulated expression of the proapoptotic caspase-3, Bax, and upregulated expression of the antiapoptotic Bcl-2. Taken together, PCr can be an effective agent for preventing cardiac fibrosis and cardiomyocyte apoptosis.

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the effect of exogenous creatine phosphate (CP) on myocardial injury after percutaneous coronary intervention (PCI)., Method: Four hundred patients were divided to receive conventional therapy (control group) or 3-day intravenous infusion of CP after PCI (CP group). Levels of creatine kinase MB (CK-MB) and troponin I (TnI) were measured before and on postprocedural day 3., Results: Postprocedural CK-MB and TnI in the CP group were significantly increased compared to the control group. In the CP group, 8.0% and 5.0% of patients had an increase in CK-MB 1 to 3 times and >3 times, respectively, which were significantly lower than that of the control group (19.0% and 9.0%, respectively); 12.0% and 10.0% of patients had an increase in TnI 1 to 3 times and >3 times, respectively, which were significantly lower than that of the control group (21.0% and 18.0%, respectively)., Conclusion: Exogenous CP was helpful to reduce myocardial injury after PCI., (© The Author(s) 2013.)

The influence of creatine or its derivates on the cell energy potential may be one of the possibl approaches to induce neuroprotection. Effect of creamide (creatinylglycine ethylic ether fumarate) on the brain injury was studied in the experimental model of the brain ischemia/reperfusion in rats. The experiments were carried out in 14-20 weeks old male Wistar rats weighing 240-300 g, anesthetized by chloral hydrate (430 mg/kg). Creamide was administered intravenously at the doses of 50, 70, 140, and 280 mg/kg. For comparison phosphocreatine was used at the dose of 255 mg/kg. Creamide and phosphocreatine were administered intravenously (in volume of 1 ml within 5 min) 30 min before cerebral middle artery occlusion. Focal cerebral ischemia for 30 min was produced by endovascular suture occlusion with the subsequent 48 h reperfusion period. Creamide administration resulted in dose-dependent decrease of brain ischemic injury. Creamide administered at the doses of 140 and 280 mg/kg was more effective as compared with phosphocreatine (255 mg/kg). The data obtained open new perspectives for further research and development of new creatine-derived drugs with neuroprotective action.

Structural changes in the heart are studied at an experimental widespread purulent peritonitis. It was established that in 6 hours after initiation of peritonitis in a myocardium the severe disorders of blood circulation, interstitial edema, the phenomena of kariopyknosis, development of systemic toxic damages specifying in high speed at this disease were observed. One of the mechanism of their development is a energy deficiency. The proof of this is destructive changes of cardiomyocytes mitochondria. The comparative analysis of use of metabolic preparations "Citoflavin", containing amber acid, and "Neoton", containing phosphocreatine, for the purpose of pharmacological support of cardiac activity at an experimental widespread purulent peritonitis has revealed high efficiency of the preparation "Citoflavin". It caused more intensive decrease of inflammatory changes in a myocardium, preventing of cardiomyocytes necrobiosis, contribution to preservation of normal structure and growth of quantity of mitochondria.

The effect of citoflavin and neoton preparations on the migration activity of neutrophil granulocytes under action of mitogen-induced immunocompetent blood cells, Peyer's patches, spleen and inguinal lymph was studied on a group of 55 male chinchilla rabbits with experimental model of widespread purulent peritonitis. It is established that the regulating action of immunocompetent cells on the migration of neutrophil leukocytes under the conditions of widespread purulent peritonitis is stable and widespread process, which is observed within 5 days of the postoperative period. The use of citoflavin and neoton during the postoperative period produces correction of the activity of immunocompetent cells, changing their properties in regulation of the migratory activity of neutrophil granulocytes. The effect is characteristic of both preparations and it is observed in all investigated organs, being manifested to a greater degree in immunocompetent cells of peripheral blood and Peyer's patches. Metabolic preparation citoflavin exhibits a more pronounced immunotropic action in comparison to neoton, which contains creatine phosphate.

The functional activity of mitochondria of the muscular coat of small intestine (MCSI) has been studied in the normal state and under experimental widespread purulent peritonitis (WPP) conditions. The experiments have been carried out on a group of 55 male rabbits of chinchilla breed. It is established that, as a result of the WPP development, the functional activity of mitochondria in MCSI considerably decreases. The comparative analysis of the efficiency of metabolic drugs cytoflavin and neoton showed advantage of the citoflavin preparation, the administration of which allowed the indices of mitochondria in intact animals to be exceeded on the fifth day of postoperative period. The research results show expediency of a complex treatment of WPP using cytoflavin preparation for the normalization of biological oxidation processes and elimination of enteric insufficiency.

Experiments on 55 male chinchilla rabbits with model widespread purulent peritonitis have been performed for determinig structural changes in adrenal glands with the aid of optical microscopy. The introduction of aerobic-anaerobic culture of E. Coli and B. Fragilis into the abdominal cavity causes expressed structural changes in parenchyma of adrenal glands within 6 hours. It is established for the first time that the administration of metabolic drugs citoflavin (containing succinic acid) and neoton (containing creatine phosphate) prevents the development of pathological structural changes in adrenal glands under conditions of experimental widespread purulent peritonitis.

The research was performed in 55 male chinchilla rabbits. For the first time the effect of metabolic preparations "citoflavin" and "neoton" of the protein-lipid spectrum of blood was studied in experimental diffuse purulent peritonitis. The development of diffuse purulent peritonitis caused negative changes in blood lipid-transport system which resulted in a decreased blood protein level and high density lipoproteins (HDL) and growth of triglycerides. In the HDL phospholipid spectrum the pathological changes are characterized by an increased lisophosphotide content and compensatory growth of the level of poliglycerophosphatides. A comparative analysis has shown that both preparations possess unidirectional action which is more pronounced in "citoflavin" than in "neoton".

Were analyzed publications devoted to the problem of diagnostics and treatment of posthypoxia myocardial ischemia. A description and estimation of the pathophysiological processes occurring in children who had perinatal hypoxia. The analysis of changes in the myocardium, and violations of intracardiac hemodynamics in newborns with posthypoxia myocardial ischemia. Describes modern methods of treatment of myocardial ischemia, including use of phosphokreatinine as a cardiotrophic therapy.

This article is report the study of the pharmacokinetics and metabolic disposition of exogenous phosphocreatine (PCr) in rats by means of an ion-pair HPLC-UV assay. PCr and its metabolite creatine (Cr) and related-ATP in rat plasma and red blood cell (RBC) were simultaneously determined. A blank plasma and RBC were initially run for baseline subtraction. Plasma and RBC samples were deproteinized with 6% PCA prior to HPLC. Following i.v. administration of PCr 500 mg x kg(-1) and 1 000 mg x kg(-1) the C-T curve could be described by the two-compartment model with t1/2beta 22.5-23.3 min, V(d) 0.956 4-0.978 6 L x kg(-1), CL 0.029 L. kg(-1) x min(-1). The Cr as PCr degraded product appeared as early as 2 min post i.v. dosing with t(max) 20 min, t1/2kappa (m) 40.6-42.7 min and f(m) 60%-76%. After po administration of PCr, the parent drug in plasma was undetectable, but the metabolite Cr was detected with t(max) 65-95 min, t1/2kappa (m) 56.0-57.7 min, metabolite-based bioavailability F(m) 55.02%-62.31%. PCr i.v. administration resulted in significant elevation of ATP level in RBC but not in plasma, the related-ATP in RBC was characterized by t(max) 68-83 min, t1/2kappa 49-52 min. In RBC no exogenous PCr was found but Cr was detected following i.v. administration of PCr, with the t(max) 120 min and t1/2k (m) 70 min for Cr. The above results indicate that PCr eliminates and bio-transforms in body very rapidly; K > K(m) confers ERL, instead of FRL, type upon the metabolic disposition of Cr. Following po administration of PCr, the degraded product Cr is absorbed but not the parent drug PCr. The formed Cr can be accounted for by most of i.v. and po PCr. Intravenous dosing leads apparently increased and sustained Cr and related-ATP concentration in RBC.

The purpose of this study was to determine the effect of 30 days of single-dose creatine supplementation with phosphate salts (CPS) on body weight (BW) and anaerobic working capacity (AWC) in men. Using a double-blind design, 32 men randomly received 1 serving of either CPS (5 g Cr + 4 g phosphate) (n = 17) or 20 g of dextrose as placebo (PL) (n = 15) for 30 days. AWC determined from the Critical Power Test and BW were measured at baseline, 10 days, 20 days, 30 days, and 10 days post-supplementation. Results (2 x 5 ANOVA) showed no significant differences between groups for AWC at any time point; however, BW was significantly increased at 10 days in the CPS group (1.0 kg) vs. PL (0.0 kg), and remained elevated for the duration of the study. These findings suggest that a single 5 g x d(-1) dose of CPS for 30 days increases BW but is not effective for increasing AWC in men.

Background/purpose: The skin has the unique ability to survive ischemia associated with skin grafts, flaps and hair transplantation procedures. Spectroscopic data later confirmed by chromatography, immunohistochemistry and molecular biology techniques identified the presence of large quantities of phosphocreatine in human skin. Phosphocreatine molecules regenerate ATP cellular reserves during ischemia. This reaction is mediated by creatine phosphokinase enzymes that were also isolated and studied in normal and diseased skin., Methods: Literature search revealed important contributions by US, Swiss, German, French, Scandinavian and Japanese investigators in the development and understanding of this research field., Results: Serum creatine phosphokinase levels are elevated in burn victims and patients with toxic epidermal necrolysis. Phosphocreatine concentration and creatine phosphokinase activity are elevated in psoriatic skin and in non-melanoma malignancies in comparison with normal skin. Furthermore, skin phosphocreatine and creatine phosphokinase enzymes are localized almost exclusively within the epidermis and in hair follicles. Finally, phosphocreatine and creatine phosphokinase enzymes help to protect skin from UV damage., Conclusions: Clearly, this research area is only starting to be appreciated by the scientific community. Topical and systemic phosphocreatine administration appears to reverse photodamage and improve wound healing. Spectroscopic monitoring of phosphocreatine and related phosphometabolites can be potentially used to monitor disease activity and respond to therapy in psoriasis, leg ulcers, skin malignancies and other skin conditions.

Aim: Off pump coronary artery bypass grafting (OPCAB) involves, and is occasionally impaired by obligatory regional myocardial ischemia, particularly with the use of proximal coronary in-flow occlusion techniques. Intracoronary shunts do not guarantee absence of distal ischemia given their small inner diameter and the presence of proximal coronary stenosis. Additional adjunctive measures to provide short-term myocardial protection may facilitate OPCAB. High-energy phosphate supplementation with creatine phosphate prior to ischemia may attenuate ischemic dysfunction., Methods: In a rodent model of a transient coronary occlusion and myocardial ischemia, 36 animals underwent preischemic intravenous infusion of either creatine phosphate or saline, 10 minutes of proximal left anterior descending (LAD) occlusion, and 10 minutes of reperfusion. Rats underwent continuous intracavitary pressure monitoring and cellular ATP levels were quantified using a luciferin/luciferase bioluminescence assay., Results: Within 2 minutes of ischemia onset, creatine phosphate animals exhibited statistically significant greater preservation of myocardial function compared to controls, an augmentation which persisted throughout the duration of ischemia and subsequent reperfusion. Furthermore, significantly greater cellular ATP levels were observed among creatine phosphate treated animals (344+/-55 nMol/g tissue, n=5) compared to control animals (160+/-9 nMol/g tissue, n=5)(p=0.014)., Conclusions: A strategy of intravenous high-energy phosphate administration successfully prevented ischemic ventricular dysfunction in a rodent model of OPCAB.

Background: The aim of this study was to characterize the muscular reservoirs of phosphorilated energetic components of athletes using 31P-MRS., Methods: The sample was formed by 14 elite athletes from the Center for High Sportive Performance (CAR, Sant Cugat del Vallés, Spain). The pattern of the phosphorilated metabolites was measured from the muscle vastus medialis by 31P-MRS. Oral supplementation of 20 g of Creatine monohydrate was given during 14 days. Two groups of athletes were formed according to their physical characteristics (weight, height, body mass index, maximum O2 uptake). The first group received a placebo (maltodextrine), while the second group received a diet of creatine supplement. The exercise was performed inside the resonance tunnel with a frequency of 60 RPM with both legs., Results: The results showed that significant decrease occurred in phosphocreatine (PCr), inorganic phosphate (Pi) and intracellular pH after supplementation., Conclusion: It was concluded that the exercise performed by the long distance runners recruited in this study, detected by 31P-MRS, reduced the consumption of PCr during exercise owing to creatine supplementation diet.

Creatine is a popular supplement used by athletes in an effort to increase muscle performance. The purpose of this review was to assess the literature evaluating the effects of creatine supplementation on renal function. A PubMed search was conducted to identify relevant articles using the keywords, creatine, supplementation, supplements, renal dysfunction, ergogenic aid and renal function. Twelve pertinent articles and case reports were identified. According to the existing literature, creatine supplementation appears safe when used by healthy adults at the recommended loading (20 gm/day for five days) and maintenance doses (

Creatine has become a popular nutritional supplement among athletes. Recent research has also suggested that there may be a number of potential therapeutic uses of creatine. This paper reviews the available research that has examined the potential ergogenic value of creatine supplementation on exercise performance and training adaptations. Review of the literature indicates that over 500 research studies have evaluated the effects of creatine supplementation on muscle physiology and/or exercise capacity in healthy, trained, and various diseased populations. Short-term creatine supplementation (e.g. 20 g/day for 5-7 days) has typically been reported to increase total creatine content by 10-30% and phosphocreatine stores by 10-40%. Of the approximately 300 studies that have evaluated the potential ergogenic value of creatine supplementation, about 70% of these studies report statistically significant results while remaining studies generally report non-significant gains in performance. No study reports a statistically significant ergolytic effect. For example, short-term creatine supplementation has been reported to improve maximal power/strength (5-15%), work performed during sets of maximal effort muscle contractions (5-15%), single-effort sprint performance (1-5%), and work performed during repetitive sprint performance (5-15%). Moreover, creatine supplementation during training has been reported to promote significantly greater gains in strength, fat free mass, and performance primarily of high intensity exercise tasks. Although not all studies report significant results, the preponderance of scientific evidence indicates that creatine supplementation appears to be a generally effective nutritional ergogenic aid for a variety of exercise tasks in a number of athletic and clinical populations.

The aim of this work was to study rationality of addition of aspartic acid, phosphocreatine, mannitol and tris(bydroxymethyl) aminomethane (trisamine) to a sanguineous cardioplegic solution. Isolated perfused rat hearts were subjected to 40-min normothermic total ischemia and 30-min reperfusion. Cardioplegic solutions were infused for 5 min prior to ischemia. A modified Ringer solution with 25 mM KCI was used as control. Osmolarity and pH of cardioplegic solutions were 340+/-5 mOms and 7.6+/-0.1 at 22 degreesC, respectively. Efficiency of myocardial protection was evaluated by recovery of contractile and pump function during reperfusion. The optimal solution contained aspartic acid (21.5 mM), mannitol (20.0 mM) and trisamine (5 mM). By the end of reperfusion the heart protected by this solution showed almost complete recovery of coronary flow (98+/-3% of the initial value vs. 77+/-3% in the control), and 2.6-fold higher recovery of stroke volume compared to the control. As a result, recovery of external cardiac work index, calculated as cardiac output-mean perfusion pressure, was 64+/-1% of the initial value vs. 24+/-5% in the control. Increase in buffer capacity of this cardioplegic solution by trisamine (up to 20.0 mM) as well as addition of phosphocreatine (10.0 mM) did not result in further augmentation of cardiac function recovery. The results suggest promising perspectives for development of medicinal form of this solution.

Experiments on noninbred albino male rats under the conditions of the whole body and the isolated isovolumically contracting heart have shown that a substantial contribution to postresuscitative cardiac damages is made by energy deficiency that triggers a group of mechanisms of damaging cardiomyocytic membranes. Exogenous creatine phosphate (CP) reduces postresuscitative mortality rates, improves bioenergy, contractile and rhythmical functions of the heart, decreases the rate of myocardial lipid peroxidation, by showing as a whole a cardioprotective action. The latter is realized by directly protecting the cardiomyocytic sarcolemma and the improvement of energy metabolism is secondary. Despite the likely mediation of this effect, improved energy metabolism is undoubtedly a key point of the protective action of exogenous CP if the heart is postresuscitatively damaged.

Usage of adenosine and high-energy phosphates in cardiac anesthesiology is widely discussed. Implementation of above substances can be achieved via three possible ways: during the preparation of patients for cardiac surgery, during surgery and after the surgery during intensive postoperative care. Optimum methods for cardiac protection, which could guarantee safe, lasting heart function preservation after the surgery are investigated till now. Advantages and disadvantages of adenosine application during preoperative and postoperative periods as well as in cardiac surgery are presented. Possibilities to use phosphocreatine for cardioprotection will be discussed as well.

Purpose: This investigation assessed the effects of a 9-wk regimen of creatine monohydrate (Cr x H2O) supplementation coupled with resistance training on body composition and neuromuscular performance in NCAA Division I football athletes., Methods: Twenty-five subjects were randomly assigned in a double-blind, randomized placebo-controlled design, to a treatment (Cr, N = 9), placebo (P, N = 8), or control group (C, N = 8). The Cr group received 20 g.d(-1) of creatine for the first 5 d in 5-g doses, four times daily, followed by 5 g.d(-1) for the remainder of the study. Each 5-g dose was mixed with 500 mL of glucose solution (Gatorade). The P group received a placebo (sodium phosphate monohydrate; NaH2PO4 x H2O) following the exact protocol as the Cr group. The C group received no supplementation. All subjects resistance trained 4 d.wk(-1). Measurements of neuromuscular performance and body composition were made pre- and post-training after supplementation while monitoring dietary intakes., Results: Repeated measures ANOVA indicated significant differences occurred between the Cr group and the other two groups (P and C) for total body weight, lean body mass, cell hydration, strength, peak torque at 300 degrees.s(-1) knee flexion, percent torque decrement, and anaerobic power and capacity. However, percent body fat, peak torque during both knee flexion and extension at 60 and 180 degrees.s(-1), peak torque at 300 degrees.s(-1) during knee extension, global muscular strength (power clean), and extracellular fluid remained statistically unchanged for all groups., Conclusions: Our findings indicate that creatine, supplemented concurrently with resistance and anaerobic training, may positively affect cell hydration status and enhance performance variables further than augmentation seen with training alone.

The ability of mechanically skinned muscle fibres from the rat to respond to T-system depolarisation was studied in relation to muscle glycogen content. Muscle glycogen was altered by incubating extensor digitorum longus (EDL) muscles in Krebs solution without glucose or in Krebs solution with glucose (10 mM) and insulin (20 U.l-1). The glycogen content of muscles stored without glucose was rather stable between 30 and 480 min (11.27 +/- 0.39 mumol.g-1), while the muscles stored with glucose and insulin maintained an elevated and stable level of glycogen (23.48 +/- 1.67 mumol.g-1) between 100 and 360 min. Single mechanically skinned fibres from paired muscles, incubated in either glucose-free Krebs or in Krebs with glucose and insulin, were subjected to cycles of T-system depolarisation-repolarisation in a controlled environment (8 mM ATP, 10 mM creatine phosphate, 1 mM Mg2+, pH 7.10) and the force response was monitored until the force had declined to 50% of the maximum response (50% rundown). Fibres from muscles with a higher glycogen content reached 50% rundown after a larger number of depolarisations and displayed consistently larger average response capacity values, calculated as the sum of the force responses to 50% rundown divided by the maximum Ca(2+)-activated force response in that fibre. Thus skinned fibres originating from muscles with a higher glycogen content have an increased ability to respond to T-system depolarisation when the effect of metabolite accumulation is minimised and the function of glycogen acting as an energy source is by-passed. This provides direct support to the hypothesis that glycogen has a protective role in maintaining fibre excitability.

The effect of acute creatine supplementation on stroke quality was investigated during simulated match play. Well-trained tennis players reported to the test center on two occasions. On each occasion they performed the Leuven Tennis Performance Test (LTPT) and a 70 m shuttle run (SHR). During 5 days prior to each test session they received in random order and according to a double-blind cross-over study design either oral creatine supplements (4 x 5 g per day) or placebo. The two experimental periods were separated by a 5-week washout period. Stroke quality was evaluated during the LTPT by means of registration of error rate and measurement of ball velocity and precision of lateral and longitudinal ball placement. Compared with placebo, creatine supplementation did not significantly impact on either power or precision of first and second services, baseline strokes in neutral and defensive rallies, and volleys. Shuttle run time was 19.87 +/- 0.30 sec during placebo versus 19.85 +/- 0.27 sec during creatine treatment. Acute creatine supplementation does not enhance stroke performance or sprint power in match-like conditions in elite tennis players.

We investigated the effect of an acute creatine loading (25 g per day for 4 days) and longer-term creatine supplementation (5 g of creatine or 5 g of placebo per day for 2 months) on the performance of 22 elite swimmers during maximal interval sessions. After the acute creatine loading, the mean of the average interval swim times for all swimmers (n = 22) improved (44.3+/-16.5 s before vs. 43.7+/-16.3 s after supplementation; P<0.01). Three of the 22 swimmers did not respond positively to supplementation. After 2 months of longer-term creatine supplementation or placebo, neither group showed a significant change in swimming performance (38.7+/-13.5 s before vs. 38.7+/-14.1 s after for the creatine group; 48.7+/-18.0 s before vs. 48.7+/-18.1 s after for the placebo group). We conclude that, in elite swimmers, 4 days of acute creatine loading improves swimming performance significantly when assessed by maximal interval sessions. However, longer-term supplementation for 2 months (5 g of creatine per day) did not benefit significantly the creatine group compared with the placebo group.

Experiments on 55 outbred adult white rats narcotized with calipsol (50 mg/kg intraperitoneally) showed that separate infusions of a synthetic creatine phosphate analog neoton (100 mg/kg) and calcium antagonist finoptin (0.1 mg/kg) into the carotid artery directly after infliction of dosed craniocerebral injury improve energy metabolism and limit the intensity of lipid peroxidation in the brain during the first hour of the posttraumatic period.

When rats bearing the 13,762 mammary carcinoma were treated with intravenously administered creatine analogs, cyclocreatine, beta-guanidinopropionic acid or creatine phosphate on days 4 through 8 and 14 through 18 post tumor implantation, the tumor growth delay produced varied with whether the animals were drinking water or sugar water over the course of the study. The tumor growth delays increased when the animals drank sugar water from 9.3, 1.6 and 7.6 days for cyclocreatine, beta-guanidinopropionic acid and creatine phosphate, respectively, to 15.0, 6.3 and 12.6 days. Blood glucose was decreased over the course of the creatine analog treatment regimen and the skeletal muscle transport protein GLUT-4 increased 1.5 to 2-fold with the creatine analog treatments. Plasma insulin was profoundly decreased to 20-25% of normal by the creatine analog treatment while plasma glucagon levels were increased. Plasma somatostatin increased 3- to 4-fold during the administration of the creatine analogs. These results implicate alterations in pancreatic hormone balance in the antitumor activity of these creatine analogs.

We investigated the effect of creatine supplementation on maximal running performance in a simulated track competition. Twelve competitive male runners were assigned to either a placebo or creatine supplementation group. Both groups completed two maximal 700-m running bouts 60 min apart on an outdoor track. A second identical trial was performed 7 days later, and for 5 days prior to the second trial, subjects ingested 20 g.day-1 of either creatine monohydrate or a placebo. Subjects in the placebo group ran 110.2 +/- 3.5 s and 110.4 +/- 3.0 s for the first trial and 108.5 +/- 2.9 s and 108.0 +/- 1.7 s for the second trial, while the creatine group ran 109.9 +/- 3.2 s and 110.4 +/- 3.6 s for the first trial and 109.7 +/- 3.3 s and 107.8 +/- 2.2 s for the second trial. There were no significant differences between groups by trial or Trial X Time for running time, postexercise blood lactate concentration, or body weight (p > .05). We concluded that creatine supplementation does not enhance performance of single or twice-repeated maximal running bouts lasting 90-120 s.

Echocardiography and integral body rheography were made in 174 patients with macrofocal myocardial infarction (MI) to study hemodynamics at six stages of hospital rehabilitation (MI day 1-28). 97 patients received neoton (4 different scheme) in the acute period of MI. Neoton administration was found to prevent progressive left ventricular dilation and emergence of cardiac insufficiency in subacute period of MI, to reduce the risk of cardiac aneurism, recurrence and postinfarction angina. The response to neoton rises with an increase of its dose on the first day of the disease and lessening of the time span from first symptoms of MI and first neoton injection. An optimal scheme of neoton use is proposed.

A key component in the development of ischemic functional and structural myocardial injury during cardiosurgical procedures is an inadequate cellular energy supply which occurs as a consequence of the cessation of oxidative metabolism. In such conditions high energy phosphates are rapidly depleted. As they play a critical role in the maintenance of cell viability and postischemic recovery of contractile function, their conservation is therefore a primary objective in any procedure designed to reduce ischemic injury. Exogenous administration of phosphocreatine (CP) has been suggested as being beneficial to the ischemic heart. The aim of present study was to evaluate the possible cardioprotective effect of exogenous CP during coronary artery surgery (CABG). Forty patients undergoing CABG procedure were randomly assigned to receive creatine phosphate-enriched (group I) or standard-St. Thomas' Hospital (group II) cardioplegic solution; each group comprised 20 patients. Group I received: 6.0 g of exogenous CP (Neoton) daily in two 20-min intravenous infusions during 3 days preoperatively; during surgical procedure they were administered standard cardioplegic solution enriched in CP at the concentration of 10 mmol/l and -- 2 days postoperatively -- 4.0 g CP daily in two intravenous injections. Group II did not receive CP at all In both groups were analysed. Haemodynamic parameters. Continuous 48-h ECG recording (Holter monitoring) outcome. Laboratory values of serum CK and CK-MB. Inotropic support required (drugs, mechanical support). Ultrastructural findings (biopsy data). Statistical analysis was carried out using Student's "t"-test and the chi2 test. Values of p<0.05 were taken as the criterion of significant difference. The results of the study were: Significantly lower average number and energy of DC-shocks needed to restore cardiac function after cardiopulmonary bypass procedure in group 1. Statistically significant beneficial effect on the presence of ventricular arrhythmias during surgery and in early postoperative period in group I. Significantly lower requirements for inotropic drugs postoperatively in group I. Statistically significant lower degree of sarcolemmal damages in myocardial biopsies in group I. Concluding, the authors wish to state that: Exogenous phosphocreatine (Neoton) perioperative administration in coronary artery bypass patients reduced the need for inotropic drugs, which is clinically manifested in lower frequency of low cardiac output syndrome. Perioperative administration of exogenous CP improves electrophysiological stability of the myocardium. Advantageous clinical and electrophysiological effect of exogenous CP may result from its properties to protect sarcolemma of the cardiomyocytes.

We used the non-invasive method of in vivo phosphorus magnetic resonance spectroscopy to investigate the effect of oral administration of phosphocreatinine on muscle energy metabolism during graded work and post-exercise recovery in humans. Phosphocreatinine administration results in a smaller depletion of phosphocreatine at high work rates accompanied by a smaller cytosolic acidification during work and recovery. Our findings suggest that oral phosphocreatinine increases the readily available energy for muscle contraction by interfering directly or indirectly with the reaction equilibria involving phosphocreatine.

To evaluate clinicohemodynamic effect of neoton (exogenic phosphocreatine) given in an intravenous course, the drug was added to standard scheme in 53 patients with chronic cardiac failure (6.0 g/day i.v. drip for 5 days or 3.0 g/day for 10 days). 20 control patients received standard therapy alone. A course neoton produced an increase in the ejection fraction, a reduction in end-diastolic and end-systolic left ventricular volumes. It is recommended to include neoton in the scheme of chronic cardiac failure treatment in the dose 3.0 g/day for 10 days.

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.

The authors submit their experience with the use of creatine phosphate in patients operated on account of coronary heart disease. They divided 50 consecutive patients into three groups. Group A--controls, group B--creatine phosphate was added to the filling of the apparatus for extracorporeal circulation and group C--creatine phosphate was added to Bretschneider's cardioplegic solution. During operation and during the early postoperative period the CK and CK MB levels were evaluated as well as levels of free acid radicals, the haemodynamic state of the patients, the incidence of ventricular dysrhythmias, the need of defibrillation, histological and histochemical examinations. The authors found a lower CK and CK MB level, a lower percentage of ventricular dysrhythmias and the same haemodynamic results of the operation in patients with a more markedly impaired systolic function of the left ventricle when creatine phosphate was used. Creatine phosphate did not affect the morphology of the heart muscle nor the level of the assessed myocardial enzymes.

The authors present the preliminary results of an experimental study where to a group of patients (n = 10) subjected to cardiosurgery, using extracorporeal circulation, to the cardioplegic solution creatine phosphate was added (Neoton of Alfa Schiaparelli Wasserman Co.)--2 g.l-1. The authors investigated haemodynamic and biochemical parameters and compared them on the day of operation with the same parameters assessed in a group of controls operated in the same way but without addition of creatine phosphate to the cardioplegic solution. Apart from insignificant differences in haemodynamic parameters the group of patients given Neoton had a lower malondialdehyde level during the early stage after termination of extracorporeal circulation, spontaneous defibrillation, a lower incidence of dysrhythmias and disorders of the conduction system. It can be assumed that creatine phosphate (Neoton) may be effective in the protection of the myocardium from ischaemia reperfusion damage.

A total of 485 patients with complicated myocardial infarction (MI) in the presence of concurrent abnormality and 104 patients with unstable angina (UA) were followed up. Intravenous infusion of neoton (phosphocreatine) in a dose of 70 g at day 1 and 36 g at days 2 and 3 of the onset was made in 96 patients with MI, 28 patients with UA took neoton in a daily dose of 30 g during 3 days. Control patients had conventional therapy, In UA, poor outcomes (death, MI, no effects, referral of patients for bypass surgery) were seen in 4 (14%) patients on the drug and in 18 (28%) in the controls (p > 0.05). In MI, more rapid disappearance of events (heart failure and tachyarrhythmias) was observed in the major group, the mortality being 23.9%, the incidence of cardiac ruptures 6.4 versus 33.6 and 12.6% respectively, in the control. It is concluded that large-dose neoton exerts positive action on the cause and outcome of UA and complicated MI.

Phosphocreatine (PC) has been widely used in cardiac surgery as a component of cardioplegic solutions because of its positive effects in preventing ischemic heart damage; we have researched the efficacy of PC in cardiac surgery when infused through the intravenous route before and after cardiac arrest. Two groups of patients who had undergone aortocoronary by-pass grafts were matched: group A (20 patients) did not receive any particular treatment; PC was administered intravenously to patients in group B after the induction of anaesthesia, immediately prior to cardiac arrest and after the release of aortic cross-clamp. To test the efficacy of the drug, the following parameters were evaluated: the recovery as the incidence of low cardiac output and/or need of inotropic drugs; dysrhythmias; electrocardiographic signs of myocardial ischemia or infarction; release of cardiac necrosis enzymes. Treated patients were found to have a better recovery, a lower incidence of dysrhythmias, an easier resumption of normal sinus rhythm with a lower number of electric defibrillations and a significantly lower release of cardiac enzymes. It can be therefore said that PC has a marked protective effect on myocardial anoxia in cardiac surgery, even when administered intravenously.

The protective effects of exogenous phosphocreatine were evaluated in vitro on isolated perfused rat hearts during reperfusion of ischemic myocardium. The hearts were randomly allocated in 2 groups. In the first (n 6) phosphocreatine was added at a concentration of 10 mM. The latter was utilized as control (n 7). In both groups the results showed a slight decrease in the post-ischemic myocardial performance. Aortic systolic pressure and flow respectively decreased on reperfusion by 17% and 12.5% in the phosphocreatine group and by 25.6% and 35% in the control group. Coronary flow was reduced by 10% in the phosphocreatine and by 18% in the control group. No statistically relevant differences were reported within or between the groups. No changes in heart rate occurred in the same period in the phosphocreatine and in the control group. Myocardial enzyme release during reperfusion showed significant lower levels of CK and LDH in the phosphocreatine group compared to controls (p less than 0.001 after 65 min and p less than 0.025 after 75 min between the 2 groups). The occurrence of serious ventricular arrhythmias was considerably higher in controls with respect to the phosphocreatine group. The overall incidence of major rhythm disturbances was 66% in the phosphocreatine group and 100% in the control group. Irreversible ventricular fibrillation (57%) occurred only in control hearts. The present findings indicate that phosphocreatine exerts a protective effect during myocardial ischemia and reperfusion, especially by preventing serious ventricular arrhythmias and by reducing myocardial enzyme release.

The situation of aggression is accompanied by metabolic alterations with an important neuro-endocrinal context. Extracorporeal surgery is an especially aggressive situation which involves both surgery and the added metabolic state of hypothermia. In 48 patients subjected to extracorporeal circulation with hypothermia, the metabolic parameters of Oxygen Consumption (VO2), Production of carbon dioxide (VCO2), Respiratory Quotient (RQ) and Energy Expenditure (GE) were studied. It was observed that the patients could be divided into two subgroups, depending on their metabolic response. Studying the RQ parameter, it was seen that this divided patients into two subgroups depending on their posterior evolution. Patients in whom RQ did not exceed 0.8 showed more favourable evolution than those in whom RQ was higher than 0.8. The correct metabolic response was regarded as a parameter indicative of the evolution, directly correlated to the hemodynamic parameters studied. In one patient, creatine phosphate was infused at a dosage of 30 mg/kg for 60 min, and an improvement was noted in GE and Cardiac Index. It was concluded that the intravenous intake of creatine phosphate in patients undergoing extracorporeal surgery improved both metabolic parameters and the myocardiac function.

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.

Experimentally, creatine phosphate (CP) added to St. Thomas' Hospital cardioplegic solution (STH) improved post-ischaemic recovery of cardiac function in the rat heart. We investigated the effect of adding CP (10.0 mmol/l) to STH. Fifty open-heart surgery patients were randomized into control (STH) and treated (STH + CP) groups (25 per group). Patients underwent (a) monitoring for peri- and postoperative arrhythmias (48-h Holter monitoring). (b) quantitative birefringence assessment of intraoperative myocardial protection in left and right ventricular biopsies sampled at start of bypass (pre-isch.), end of bypass (end-isch.) and after 10 min reperfusion (post-isch.), and (c) measurement of serum creatine kinase-MB isozyme (CK-MB) values for up to 4 days postoperatively; results were assessed with respect to (d) haemodynamics and postoperative clinical outcome. Inotropic support (adrenaline) was required in three patients (12%) from each group; no patient died. All patients required defibrillation, and the number of direct current shocks required for sinus rhythm was the same in each group. The occurrence and incidence of reperfusion-induced arrhythmias were the same in both groups. Serum CK and CK-MB values were similar throughout the sampling period in both groups of patients; one patient in the control group had raised CK-MB levels postoperatively, but perioperative infarction was not indicated by the electrocardiogram.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Ultrastructural changes in normal and hypertrophied dog hearts under conditions of total ischemia were studied by electron microscope method. In the control group sings of irreversible damage appeared in 90 min, in the presence of phosphocreatine, 10 mM, these changes became apparent in 120 min. In the hypertrophied hearts signs of the irreversible damages became evident in 60 and 90 min in the absence and presence of phosphocreatine, respectively. Ability of phosphocreatine to protect both normal and hypertrophied myocardium allows to use it safely.

The combined effect of glutamic acid (15 mM) and phosphocreatine (10 mM) on metabolism and postischemic recovery of cardiac function was studied in isolated perfused working guinea pig hearts. Addition of these two agents into standard hyperpotassium cardioplegic solution increased twice the recovery of the aortic output and improved restoration of volume work and an index of functional recovery. This effect was combined with the complete recovery of ATP, phosphocreatine, the decrease in ammonia and lactate tissue contents and preservation of amino acid pool. Lesser leakage of creatine and creatine kinase pointed to lesser damage of the sarcolemma. The results show the effectiveness of the use of cardioplegic solution containing both glutamic acid and phosphocreatine.

Results of morphological and biochemical examination of 153 myocardium biopsies from 42 patients with the intraoperational heart ischemia that developed during the correction of cardiac valves disturbances under the condition of artificial circulation and cardioplegia with the blood based solution are given. Phosphocreatin ("neoton" produced by Schiapparelli Company, Italy) was added as a cardioprotector to the cardioplegic solution in 24 patients. The high efficiency of the drugs for the cardiomyocytes sarcolemma is shown by means of colloidal lanthanum. A full retention of the macroergic phosphates is also shown biochemically when the standard solution was modified for the heart protection.