Creatine Phosphate Group Research Articles

Protective Effect of Xinmailong Injection on Rats With Myocardial Infarction.

This study aimed to investigate the protective effect of Xinmailong injection on rats with myocardial infarction. Thirty-six rats were induced myocardial infarction by operation, and six underwent sham operation. The myocardial infarction rats were randomly divided into three groups, 12 in each, and administered intraperitoneal injection of Xinmailong 5 mg/(kg·d), sodium creatine phosphate 80 mg/(kg·d), or normal saline as control respectively for 14 days. When the treatments were completed, the hemodynamic parameters of the rats were observed, and blood samples were taken to examine blood routine, blood coagulation index, liver and kidney function, inflammatory index, myocardial marker, thrombo-elastography, and other indicators. The morphology of cardiomyocytes was observed through light microscopy, and the microstructure of the myocardial cells was observed under electron microscope. No significant difference was found in blood routine, liver and kidney function, and blood coagulation index between the Xinmailong and sodium creatine phosphate groups compared with the saline control group. However, the inflammatory index and levels of myocardial markers were significantly decreased, and cardiac function was significantly improved. In terms of the morphology of myocardial cells, the Xinmailong group was similar to the sodium creatine phosphate group, the myocardial cell membrane was protected, and myocardial cell damage was reduced. In conclusion, Xinmailong is safe and had anti-inflammatory, heart-improving, and myocardial-protective effects. Its effectiveness is not inferior to that of sodium creatine phosphate.

Effect of creatine phosphate on myocardial injury induced by lung ischemia-reperfusion in rats

Objective To evaluate the effect of creatine phosphate on the myocardial injury induced by lung ischemia-reperfusion (I/R) in rats. Methods Twenty-four male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-350 g, were randomly divided into 3 groups (n=8 each) using a random number table: sham operation group (group S), I/R group, and I/R+ creatine phosphate group (group CP). Lung I/R was induced by clamping the left hilum of lung for 0.5 h with a non-invasive microvascular clip followed by mechanical ventilation and 2.0 h of reperfusion.Creatine phosphate 6.6 mg·kg-1·min-1 were infused intravenously at 30 min before ischemia in group CP, while the equal volume of normal saline was administered in group I/R.At 2.0 h of reperfusion, blood samples were obtained from the right ventricle for determination of the serum concentration of cardiac troponin I (cTnI). Myocardial specimens were obtained from the apex for microscopic examination and for determination of the levels of myocardial superoxide dismutase (SOD), malondialdehyde (MDA), and myeloperoxidase (MPO). Results Compared with group S, the serum cTnI concentrations, MDA content, and MPO activity were significantly increased, and the SOD activity was significantly decreased in I/R and CP groups (P<0.05). Compared with group I/R, the serum cTnI concentrations, MDA content, and MPO activity were significantly decreased, and the SOD activity was significantly increased in group CP (P<0.05). Myocardial injury was significantly attenuated in group CP as compared with group I/R. Conclusion Creatine phosphate can attenuate the myocardial injury induced by lung I/R in rats, and the mechanism is related to decrease in damage caused by lipid peroxidation. Key words: Phosphocreatine; Lung; Reperfusion injury

The Effect of Exogenous Creatine Phosphate on Myocardial Injury After Percutaneous Coronary Intervention

To evaluate the effect of exogenous creatine phosphate (CP) on myocardial injury after percutaneous coronary intervention (PCI). 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. 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). Exogenous CP was helpful to reduce myocardial injury after PCI.

The value of creatine phosphate GIK in cardiac valve disease before operation

Objective To investigate the myocardial protection on cardiac valve replacement surgery with creatine phosphate of myocardial GIK (GIK) in order to reduce the surgical risk and improving the efficacy.Methods 126 cases were unergone surgical treatment of heart valve disease,whose cardiac function on admission wereⅢor Ⅳ. 126 patients were randomly divided into two groups. Cardiopulmonary bypass time, aortic cross clamp time, postoperative myocardial injury markers ( CK-MB, cTNI) changes, arrhythmias, heart function recovery, length of stay and mortality rate and other indicators were compared between the two groups. Results The age, gender, body mass,heart disease and surgery combined data were not statistically significant between the two groups( all P ＞0. 05). The cardiopulmonary bypass time, aortic cross clamp time and mortality had no significant differences between the two groups( all P ＞ 0.05 ). The CK-MB( 21.36± 9.21 ) U/L and cTNI(0.83 ± 0. 35 ) ng/ml of creatine phosphate group were significantly lower than those of the control group. The incidence of arrhythmia in phosphocreatine group (37. 1％ ) was significantly lower than ordinary group (57.8 ％ ) ( X2 ＝ 5. 418, P ＜ 0. 05 ). Conclusion The application of creatine phosphate GIK before valve replacement surgery could effectively reduce reperfusion injury after myocardial ischemia,myocardial protection,and significantly reduce the incidence of arrhythmia and improve heart function in patients. Key words: Heart valve disease; GIK liquid; Phosphocreatine

Effects of phosphocreatine on apoptosis following myocardial ischemia-reperfusion in diabetic melllitus rats

Objective To investigate the effects of phosphocreatine on apoptosis following myocardial ischemia-reperfusion (I/R) in diabetic rats. Methods Male SD rats weighing 150-170 g were used in this study.Diabetes mellitus was induced by high fat diet and intraperitoneal streptozotocin. Twenty-seven rats in which diabetes mellitus was successfully induced were randomly divided into 3 groups ( n = 9 each): sham operation group (group S);myocardial I/R group(group I/R )and phosphocreatine group (group PP). Myocardial I/R was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 2 h reperfusion in I/R and PP groups. In group PP phosphocreatine 1 g/kg was given intraperitoneally 30 min before myocardial I/R. Blood samples were collected at the end of 2 h reperfusion for determination of plasma concentration of calcium troponin T (cTnT). The animals were then sacrificed and iscbemic myocardial specimens were isolated. The expression of Bcl-2, Bax and Caspase-3 in isehemic myocarcdium was determined and Bcl-2/Bax ratio was calculated. Myocardial apoptosis was detected by TUNEL and apoptotic index was calculated. The ultrastructure of cardiomyocytes was examined with electron microscope. Results Myocardial I/R significantly increased plasma cTnT concentration and Bcl-2, Bax and Caspase-3 expression in myocardium and apoptosis index and decreased Bcl-2/Bax ratio. Phosphocreatine significantly attenuated I/R-induced above-mentioned changes and myocardial damage. Conclusion Phosphocreatine can reduce myocardial I/R injury in diabetic mellitus rats by reducing myocardial apoptosis through up-regulation of Bcl-2 expression and down-regulation of Bax and Caspase-3 expression. Key words: Phosphocreatine; Diabetes mellitus, experimental; Myocardial repeffusion injury; Apoptosis

Effect of creatine phosphate on perioperative myocardial injury caused by living donor fiver transplantation in adult patients

Objective To investigate the effect of creatine phosphate on perioperative myocardial injury caused by living donor liver transplantation(LDLT)in adult patients.Methods Forty ASA Ⅱ -Ⅳ patients(liver function Child-Pugh grade B or C)aged 45-62 yr weighing 47-91 kg undergoing LDLT were randomly divided into 2 groups(n = 20 each): control group(group C)and creatine phosphate group(group CP).In group CP,creatine phosphate 30 mg/kg was injected intravenously at skin incision followed by creatine phosphate infusion at 4 mg· kg- 1 · h- 1 until the end of surgery.In group C,equal volume of normal saline was infused instead of creatine phosphate.HR,MAP,CVP,PCWP,CO and SvO2 were recorded immediately before skin incision,at 5 and 30 min of anhepatic phase,at 5 and 30 min of neohepatic phase and at the end of operation.Blood samples were taken from central vein immediately before skin incision(baseline,T0),at 30 min of anhepatic phase(T1),at 30min of neohepatic phase(T2),at the end of operation(T3)and at 4 and 24 h after operation(T4,5)for determination of serum cardiac troponin I(cTnI)and creatine kinase MB(CK-MB)concentrations and lactate dehydrogenase(LDH)activity.Postoperative adverse events were recorded.Results The serum cTnI and CK-MB concentrations and LDH activity were significantly increased at T2-5 as compared with the baseline value at T0 in both groups(P ＜0.05 or 0.01).MAP and CO were significantly higher from 5 min of neohepatic phase to the end of operation,the serum cTnI and CK-MB concentrations and LDH activity were significantly lower at T2-5,and the incidence of ventricular arrhythmia was significantly lower in group CP than in group C(P ＜ 0.05 or 0.01).Conclusion Creatine phosphate can attenuate perioperative myocardial injury caused by LDLT in adult patients. Key words: Phosphocreatine; Liver transplantation; Myocardial reperfusion injury

Effect of large dose creatine phosphate on myocardial ischemia-reperfusion injury in patients undergoing cardiac valve replacement

Objective To investigate the effect of high-dose creatine phosphate (CP) on myocardial ischemia-reperfusion (I/R) injury in patients undergoing cardiac valve replacement. Methods Two hundred and forty-six ASA Ⅱ or Ⅲ patients aged 42-71 yr weighing 45-80 kg undergoing mitral-aortic valve replacement were randomly assigned into 2 groups: control group ( n = 122) and CP group ( n = 124). CP 10 g in 100 ml normal saline (NS) was infused over 60 min starting from the beginning of operation in group CP. In control group NS 100 ml was infused instead of CP. Blood samples were collected before anesthesia and on 1st and 5th postoperative day for determination of serum CK, CK-MB and LDH activity and cTnI concentration. The number of patients receiving dopamine and adrenaline at the time of return of spontaneous heart beat and 12, 24 and 48 h after operation was recorded. The incidence of arrhythmia (auricular fibrillation, ventricular arrhythmia), myocardial infarct and left ventricular ejection fraction (LVEF) were also compared between the 2 groups. Results Serum CK, CK-MB and LDH activity and cTnI concentration on 1st and 5th postoperative day, the doses of dopamine and adrenalin, the incidence of arrhythmia and myocardial infarct were significantly lower in group CP than in control group. The postoperative LVEF and the incidence of spontaneous recovery of spontaneous heart-beat were significantly higher in group CP than in control group. Conclusion Pretreatment with high dose CP can protect myocardium against I/R injury in patients undergoing cardiac valve replacement under CPB. Key words: Phosphocreatine; Heart valve prosthesis; Myocardial reperfusion injury

Quantitative 1HMRS and MRI Volumetry Indicate Neuronal Damage in the Hippocampus of Children with Focal Epilepsy and Infrequent Seizures

Seizures induce progressive morphologic and functional changes in particular in the hippocampus, but whether and at what stage the hippocampus is affected in children with focal, temporal, nonintractable epilepsy is poorly known. We have now studied eventual metabolic and volume changes in the hippocampus of children with nonsymptomatic focal epilepsy taking antiepileptic medication (AEDs) but still having infrequent seizures. Quantitative proton magnetic resonance spectroscopy ((1)HMRS) and volumetric MRI were used to study the hippocampal region of 11 pediatric outpatients (age 10 to 17 years) with cryptogenic localization-related epilepsy, and eight healthy volunteers (age 9 to 16 years) served as controls. The spectra were obtained bilaterally from the hippocampi by using the 1.5-T MR imager. The spectral resonance lines of N-acetyl group (NA), creatine and phosphocreatine group (Cr), choline-containing compounds (Cho), and myoinositol (mI) were analyzed quantitatively. The volume of the hippocampus was semiautomatically calculated. The mean concentration of NA was significantly decreased both in the focus side (9.02 +/- 2.00 mM) and in the nonfocus side (8.88 +/- 2.09 mM) of the patients compared with the controls (10.76 +/- 1.86 mM), in particular if the children had a history of generalized tonic-clonic seizures. The mean concentrations of Cho, Cr, and mI did not differ significantly between the patients and controls. Moreover, the mean hippocampal volume of the focus side of patients was significantly reduced compared with that of the controls. Metabolic changes in hippocampi were detected in children with nonsymptomatic localization-related epilepsy and infrequent seizures. Reduced NA could reflect neuronal metabolic dysfunction and/or neuronal damage, as indicated by our volumetric findings.

Clinical Study of the Protective Effect of Exogenous Creatine Phosphate on Ischemic Myocardium during Open Heart Surgery

This study was designed to evaluate the myocardial protective effect of exogenous creatine phosphate (CP) added to cardioplegic solution for use in open heart surgery. Ninety-eight patients were divided into a control group (n = 44) and a CP group (n =54). The spontaneous recovery rate of heart beat after aortic declamping was recorded and changes of serum enzymes including CPK, LDH, CPK-MB, HBDH, and AST were evaluated. The ultrastructural alterations of the myocardial tissue were observed in 4 patients (2 cases from each group) who had cardiac valve replacement. The spontaneous recovery rate of heart beat in the CP group was significantly higher than the control group (39/54 versus 22/44 ), and the peak values of leakage of serum enzymes of the control group appeared earlier and receded later than those of the CP group. Electron microscope examination revealed better preservation of the ultrastructures of the myocardial tissue in the CP group than that of the control group. This data indicates that exogenous creatine phosphate added to the cardioplegic solution offers a better protective effect on the ischemic myocardium during open heart surgery.

Multicenter controlled study of creatine phosphate in the treatment of heart failure

A multicenter trial was conducted in patients with heart failure to evaluate the effects of creatine phosphate in addition to conventional therapy (ie, digitalis, diuretics, nitrates). Clinical symptoms and New York Heart Association (NYHA) classes, electrocardiographic (ECG) signs of ischemia, and use of sublingual nitroglycerin were evaluated. A total of 1,007 patients were entered in the study; 508 patients were randomized to receive creatine phosphate (CP) 1 gm twice daily intravenously for 2 weeks followed by 1 month of CP at a daily dose of 500 mg intramuscularly in addition to conventional therapy and 499 patients in the control group were treated with conventional therapy only. Both groups were comparable with regard to sex, age, study period, type of drugs used, and pathogenesis of heart failure. At the beginning of the study, clinical conditions and ECG parameters were not statistically different between groups. During the study period, the number of patients in NYHA classes III and IV decreased significantly more in the CP group than in the control group. The clinical symptoms of heart failure (dyspnea, pulmonary stasis, and peripheral edema), the main signs of ischemia (angina pectoris, number of patients taking sublingual nitroglycerin, negative T wave), and the incidence of ventricular premature beats improved significantly more in the CP group than in the control group.

Creatine phosphate: An additive myocardial protective and antiarrhythmic agent in cardioplegia

The potential for enhancing myocardial protection by adding high-energy phosphates to cardioplegic solutions was investigated in a rat heart model of cardiopulmonary bypass and ischemic arrest. Creatine phosphate (CP) was evaluated as an additive to the St. Thomas' Hospital cardioplegic solution. Dose-response studies (CP 0 to 50 mmol/L) revealed 10.0 mmol/L as the optimal concentration which improved recovery of aortic flow and cardiac output after a 40 minute period of normothermic (37 degrees C) ischemic arrest from 21.2% +/- 5.4% and 32.8% +/- 4.6% in the CP-free control group to 82.5% +/- 3.7% and 82.6% +/- 4.2% (p less than 0.001), respectively. Creatine kinase (CK) leakage was reduced by 68.7% (p less than 0.001) in the CP group. With hypothermic (20 degrees C) ischemia (240 minutes) and multidose (every 30 minutes) cardioplegia, recoveries of aortic flow and cardiac output were improved from 33.1% +/- 8.4% and 42.2% +/- 7.7% in the CP-free control group to 77.9% +/- 4.2% and 79.6% +/- 4.3% (p less than 0.001), respectively, in the drug group. In addition to improving function and decreasing CK release, CP reduced reperfusion arrhythmias, significantly decreasing the time between cross-clamp removal and return of regular rhythm and also completely obviating the need for electrical defibrillation. 51Chromium-ethylenediaminetetraacetic acid (51Cr-EDTA), an extracellular space marker, was used to study the disappearance of CP from the cardioplegic solution during its stasis in the heart. Upon reperfusion, two thirds of the infused dose appeared unchanged in the coronary effluent; the remainder was either degraded or accumulated by the myocardium. Despite its alleged inability to enter the myocardial cell, exogenous CP exerts potent protective and antiarrhythmic effects when added to the St. Thomas' Hospital cardioplegic solution. Although the mechanism of action remains to be elucidated, it may involve binding or uptake of the drug.