Yi-Qi-Fu-Mai (YQFM) is extensively used clinically to treat cardiovascular diseases in China. To explore the anti-hypoxia effect of the extract of YQFM preparation (EYQFM), the EYQFM (1.4, 2.8, and 5.5 g·kg(-1)·d(-1)) was assessed for its heart-protective effect in a chronic intermittent hypoxia (CIH) animal model (oxygen pressure 7%-8%, 20 min per day) for 28 days of treatment. Betaloc (0.151 6 g·kg(-1)·d(-1)) was used as a positive control. The histopathological analyses of heart in CIH mice were conducted. Several cardiac state parameters, such as left ventricular ejection fractions (EF), stroke volume (SV), expression of creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured. The results showed that treatment with EYQFM markedly reversed swelling of the endothelial cells and vacuolization in the heart when compared with the model group. Further study demonstrated that EYQFM significantly improved ventricular myocardial contractility by increasing EF and SV. In addition, EYQFM inhibited the activity of CK, LDH, decreased the level of MDA and improved SOD activity. The results demonstrated that EYQFM significantly improved the tolerability of myocardium to hypoxia and ameliorated the cardiac damage in the CIH model.
Animals ; Creatine Kinase ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Heart ; drug effects ; Heart Injuries ; enzymology ; etiology ; metabolism ; prevention & control ; Humans ; Hypoxia ; complications ; L-Lactate Dehydrogenase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mice ; Superoxide Dismutase ; metabolism

To explore the effect of long-time propofol infusion on myocardial enzymes, mitochondrial cytochrome C and ATP in rabbits. 
 Methods: A total of 18 New Zealand rabbits were randomly divided into 3 groups: a control group, a propofol group and an intralipid group. The rabbits were continuously infused with 0.9% normal saline in the control group, 1% propofol in the propofol group, and 10% intralipid in the intralipid group, respectivey. The arterial blood was collected at 0, 8, 16 h and the end of experiment to examine creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). In the end, the myocardial mitochondria from myocardial tissues was separated by differential centrifugation, and mitochondrial cytochrome C content and adenosine triphosphate (ATP) levels were examined by high performance liquid chromatography.
 Results: Compared with the control group, the release of cytochrome C from mitochondria were increased in the propofol group and the intralipid group (both P<0.05), but there was no significant difference between them (P>0.05). There was also no significant difference in the ATP content of the mitochondria among the 3 groups (P>0.05). The levels of CK were increased at 8, 16 and 24 h after infusion in the propofol group and the intralipid group compared with that before the infusion (all P<0.05); compared with the control group, the levels of CK were increased at 8, 16 and 24 h after infusion in the propofol group and the intralipid group (all P<0.05); compared with the intralipid group, the levels of CK were increased at 8, 16 and 24 h after infusion in the propofol group (all P>0.05); compared with the control group, the levels of CK-MB were obviously increased in the infusion of propofol for 24 h in the propofol group (P<0.05).
 Conclusion: The levels of serum CK increase after the infusion of propofol and intralipid for a long time, and the levels of CK-MB also elevate in the infusion of propofol. Propofol and intralipid can increase the release of myocardial mitochondrial cytochrome C, but they don't affect the ATP production in myocardial mitochondrial.
Adenosine Triphosphate ; metabolism ; Animals ; Creatine Kinase ; blood ; metabolism ; Creatine Kinase, MB Form ; blood ; metabolism ; Cytochromes c ; metabolism ; Emulsions ; administration & dosage ; pharmacology ; Infusions, Intravenous ; Mitochondria ; drug effects ; Myocardium ; chemistry ; enzymology ; Phospholipids ; administration & dosage ; pharmacology ; Polyphosphates ; Propofol ; administration & dosage ; pharmacology ; Rabbits ; Soybean Oil ; administration & dosage ; pharmacology

To investigate the protective effect of preconditioning with hyperoside ( Hyp) against myocardial ischemia-reperfusion injury (MIRI) in rats and the role of PI3K/Akt signaling pathway. MIRI was established by ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 120 min in rats. Male SD rats were randomly divided into five groups: sham group,model group (MIRI),Hyp preconditioning group(Hyp), Hyp preconditioning + LY294002 (a PI3K/Akt signaling pathway inhibitor) group (Hyp + LY), and LY294002 group (LY). At the end of reperfusion, hemodynamic parameters were recorded as left ventricular systolic pressure (LVSP) , left ventricular end-diastolic pressure ( LVEDP) and maximal rate of increase and decrease of left ventricular pressure (± dP/dt(max)). Myocardial infaret size, the oxidative stress markers, myocardial enzymes indicators and inflammatory factors were also analyzed. The expressions of Akt, p-Akt, Bax and Bcl-2 proteins was detected by using Western blot method. The results showed that Hyp preconditioning remarkably improved cardiac constriction and relaxation function, reduced myocardial infarct size and enhanced the activities of oxidative stress markers about correlated to MIRI, such as superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px) and decreased the contents of malondialdehyde (MDA) as compared with MIRI group. Simultaneouly, the levels of myocardial enzymes, i. e. creatine kinase ( CK) and creatine kinase MB isoenzyme (CK-MB), and inflammatory factors, for instance tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were decreased. Hyp pretreatment apparently restrained myocardial apoptosis as evidenced by decreasing the level of Bax expression, increasing the levels of phosphorylation of Akt and Bcl-2 expression. These effects were inhibited by LY294002, a blocker of PI3K/Akt signaling pathway. These findings indicated that the cardioprotection of Hyp preconditioning against MIRI may be related to activating PI3K/Akt signaling pathway, upregulating the expression of BCL-2 protein and down-regulating the expression of Bax protein.
Animals ; Creatine Kinase ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Heart ; drug effects ; Humans ; Interleukin-6 ; genetics ; metabolism ; Ischemic Preconditioning, Myocardial ; Male ; Malondialdehyde ; metabolism ; Myocardial Reperfusion Injury ; drug therapy ; enzymology ; genetics ; prevention & control ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Quercetin ; administration & dosage ; analogs & derivatives ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; genetics ; metabolism

To study the therapeutic effect and possible mechanism of icariin on myocardial ischemia-reperfusion injury ( MIRI) model in diabetes rats. The model of diabetic rats were induced by Streptozotocin (STZ), then the model of MIRI was established by ligating the reversible left anterior descending coronary artery for 30 min, and then reperfusing for 120 min. totally 40 male SD were randomly divided into five groups: the control group (NS), the ischemia reperfusion group (NIR), the diabetes control group (MS), the diabetic ischemia reperfusion group (MIR) and the diabetic ischemia reperfusion with icariin group (MIRI). The changes in blood glucose, body weight and living status were observed; the enzyme activity of serum CK-MB, LDH, GSH-Px and myocardium SOD and the content MDA and NO in myocardium were detected; the myocardial pathological changes were observed by HE staining; the myocardial Caspase-3, the Bcl-2, Bax protein expressions were detected by Western blot. The result showed that the diabetes model was successfully replicated; myocardial ischemia-reperfusion injury was more serious in diabetes rats; icariin can increase NO, SOD, GSH-Px, Bcl-2 protein expression, decrease MDA formation, CK-MB and LDH activities and Caspase-3 and Bcl-2 protein expressions and myocardial damage. The result suggested that icariin may play a protective role against ischemia reperfusion myocardial injury in diabetes rats by resisting oxidative stress and inhibiting cell apoptosis.
Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Creatine Kinase ; metabolism ; Diabetes Mellitus, Type 2 ; complications ; Drugs, Chinese Herbal ; administration & dosage ; Flavonoids ; administration & dosage ; Humans ; Ischemia ; drug therapy ; etiology ; physiopathology ; Male ; Malondialdehyde ; metabolism ; Myocardial Reperfusion Injury ; drug therapy ; etiology ; metabolism ; physiopathology ; Myocardium ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; bcl-2-Associated X Protein ; metabolism

The safety, tolerability and immunogenicity of an oral cholera vaccine (OCV) was assessed in adult Korean male through an open-label, non-comparative clinical study. Two doses of vaccine with an interval of 2 weeks were given to 20 healthy subjects. A total of 7 adverse events occurred in 6 subjects. However, no clinically significant change was observed in electrocardiograms, vital signs, physical examinations, and clinical laboratory tests. The immunogenicity of OCV was evaluated by serum vibriocidal assay where anti-Vibrio cholerae O1 and O139 antibodies were measured at day 0, 14, and 28 of vaccine administration. The antibody titers ranged from < 2.5-5,120 for V. cholerae O1 Inaba, < 2.5-10,240 for V. cholerae O1 Ogawa and < 2.5-480 for V. cholerae O139. In addition, the fold increase in antibody titers ranged from 1-4,096 for O1 Inaba, 1-8,192 for O1 Ogawa, and 1-384 for O139. The seroconversion rate was 95% and 45% for O1 and O139 antibodies, respectively. Our study clearly shows that administration of two doses of OCV at a 2 week-interval increases an appropriate level of antibody titer in the serum of healthy Korean adult males (Clinical Trial Number, NCT01707537).
Administration, Oral ; Adult ; Antibodies, Bacterial/*blood/immunology ; Antibody Formation ; Cholera/*prevention & control ; Cholera Vaccines/adverse effects/*immunology ; Creatine Kinase/blood ; Humans ; Male ; Republic of Korea ; Toothache/etiology ; Vibrio cholerae O1/immunology

To study the antiarrhythmic effect of the newly developed alpha/beta-blocker TJ0711, a variety of animal models of arrhythmia were induced by CaCl2, ouabain and ischemia/reperfusion. Glass microelectrode technique was used to observe action potentials of right ventricular papillary muscle of guinea pig. The onset time of arrhythmia induced by CaCl2 was significantly prolonged by TJ0711 at 0.75, 1.5 and 3 mg x kg(-1) doses. TJ0711 (1.5 and 3 mg x kg(-1)) can significantly shorten the ventricular tachycardia (VT) and ventricular fibrillation (VF) duration, the incidence of VF and mortality were significantly reduced. On ischemia-reperfusion-induced arrhythmic model, TJ0711 (0.25, 0.5, 1 and 2 mg x kg(-1)) can significantly reduce the ventricular premature contraction (PVC), VT, VF incidence, mortality, arrhythmia score with a dose-dependent manner. At the same time, rats serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities decreased significantly by TJ0711 (1 and 2 mg x kg(-1)). Ouabain could cause arrhythmia in guinea pigs, when TJ0711 (0.375, 0.75, 1.5 and 3 mg x kg(-1)) was given, the doses of ouabain inducing a variety of arrhythmia PVC, VT, VF, cardiac arrest (CA) were significantly increased with a dose-dependent manner. In the TJ0711 0.1-30 micromol x L(-1) concentration range, guinea pig right ventricular papillary muscle action potential RP (rest potential), APA (action potential amplitude) and V(max) (maximum velocity of depolarization) were not significantly affected. APD20, APD50 and APD90 had a shortening trend but no statistical difference with the increase of TJ0711 concentration. TJ0711 has antiarrhythmic effect on the sympathetic nerve excitement and myocardial cell high calcium animal arrhythmia model. Myocardial action potential zero phase conduction velocity and resting membrane potential were not inhibited by TJ0711. APD20, APD50 and APD90 were shortened by TJ0711 at high concentration. Its antiarrhythmic action mechanism may be besides the action of blocking beta1 receptor, may also have a strong selective blocking action on alpha1 receptor and reducing intracellular calcium concentration.
Action Potentials ; drug effects ; Adrenergic alpha-Antagonists ; administration & dosage ; pharmacology ; Adrenergic beta-Antagonists ; administration & dosage ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; administration & dosage ; pharmacology ; Arrhythmias, Cardiac ; blood ; chemically induced ; etiology ; pathology ; physiopathology ; Calcium Chloride ; Creatine Kinase ; blood ; Dose-Response Relationship, Drug ; Female ; Guinea Pigs ; Heart Ventricles ; cytology ; Lactate Dehydrogenases ; blood ; Male ; Myocardial Reperfusion Injury ; complications ; Myocytes, Cardiac ; drug effects ; physiology ; Ouabain ; Papillary Muscles ; cytology ; Phenoxypropanolamines ; administration & dosage ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Statins are commonly used in the treatment of hyperlipidaemia. Although the benefits of statins are well-documented, they have the potential to cause myopathy and rhabdomyolysis due to the complex interactions of drugs, comorbidities and genetics. The cytochrome P450 family consists of major enzymes involved in drug metabolism and bioactivation. This article aims to highlight drug interactions involving statins, as well as provide updated recommendations and approaches regarding the safe and appropriate use of statins in the primary care setting.
Aged ; Clarithromycin ; administration & dosage ; Colchicine ; administration & dosage ; Creatine Kinase ; metabolism ; Cytochrome P-450 CYP3A ; metabolism ; Drug Interactions ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; administration & dosage ; Lovastatin ; administration & dosage ; Muscle Weakness ; chemically induced ; Muscles ; drug effects ; Myalgia ; chemically induced ; Patient Safety

BACKGROUND: Analyzing large numbers of specimens in a short time and generating accurate results while minimizing costs are critical to laboratory tests. The CS-6400 (Dong-A Dirui, China), an automated chemistry analyzer, has been recently developed in China in collaboration with domestic corporations. To assess the performance and usability of the analyzer, we evaluated its analytical performance and clinical usefulness including accuracy and linearity of electrolytes and chemistry tests using HiSens reagent (HBI Co., Korea) with protocols provided by the Clinical and Laboratory Standards Institute, and compared these results with those of the formerly used DXC800 (Beckman Coulter, USA), and Vista500 (Siemens, Germany). METHODS: The accuracy, linearity, recovery factor, and sample carryover of the CS-6400 using HiSens reagent were determined for 29 tests-aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase, glucose, total cholesterol, triglyceride (TG), amylase, lipase, creatine kinase (CK), blood urea nitrogen, creatinine, uric acid, total protein, albumin, total bilirubin (TB), direct bilirubin (DB), calcium, inorganic phosphorus, magnesium (MG), HDL cholesterol, rheumatoid factor (RF), LDL cholesterol, C-reactive protein, anti-streptolysin O, sodium, potassium, and chloride and the results were compared with the values obtained from the DXC800 and Vista500 to set reference intervals for each test. Serum samples obtained from 128 healthy adults were used for the reference intervals. and values obtained from DXC800 and Vista500 were used to make comparison on and to set reference intervals for each routine. Serum specimens obtained from a total of 128 healthy adults were used for the reference intervals. RESULTS: The coefficient of variation showed excellent values of < or =5% for all tests except ALP, DB, MG, RF, TB, and TG (> or =5%). The coefficient of determination (R2) was > or =0.993 with linearity between 0.928 and 1.078 within the useful clinical span. In addition, the recovery factor values of the tests were 84% to 108%, and correlation comparisons were 0.975 except for albumin (0.9516), RF (0.7617), and LDL cholesterol (0.9709). We evaluated whether the CS-6400 contributed to the attempt to minimize the test's cost and running time. Developed in China, the CS-6400 has been approved by the Food and Drug Administration and uses indirect ion selective electrodes for electrolytes and colorimetry and turbidimetry for general and specific chemistry items. The tests showed excellent linearity of > or =0.993 using commercial certified linearity material. The recovery factor values of the tests were 93% to 108%, except for LDL cholesterol (84%). Except for the minimum values, percentage sample carryover values for CK and LDH were < or =1% (0.00% and 0.07%, respectively), suggesting that the results of the tests were not affected by sample carryover, and reference interval was present based on sex. CONCLUSIONS: The CS-6400 with HiSens showed excellent analytical performance (precision, linearity, and accuracy). Furthermore, results from the CS-6400 were highly correlated with those obtained from similar tests performed on DXC800 and Vista500. Therefore, the CS-6400 is appropriate for tertiary care hospitals where large volumes of test samples must be processed within a short period with minimal cost.
Adult ; Alanine Transaminase ; Alkaline Phosphatase ; Amylases ; Bilirubin ; Blood Urea Nitrogen ; C-Reactive Protein ; Calcium ; China ; Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Colorimetry ; Cooperative Behavior ; Creatine Kinase ; Creatinine ; Electrolytes ; Glucose ; Humans ; Ion-Selective Electrodes ; L-Lactate Dehydrogenase ; Lipase ; Magnesium ; Nephelometry and Turbidimetry ; Phosphorus ; Potassium ; Rheumatoid Factor ; Running ; Sodium ; Tertiary Healthcare ; Transferases ; United States Food and Drug Administration ; Uric Acid

OBJECTIVETo investigate the effect of Shuangshen Ningxin (SSNX) formula on energy metabolism of myocardial ischemia/reperfusion rats.

METHODThe myocardial ischemia/reperfusion model of Wistar rats was established through the ligation of left anterior descending branch of coronary artery of for 40 min and the reperfusion for 2 h. The Wistar rats were randomly divided into six groups: the sham operation group, the model group, the Trimetazidine group (10 mg x kg(-1)) and SSNX groups (22.5, 45, 90 mg x kg(-1)). Preventive administration was conducted for 5 d. The operation was performed at 1 h on the day of the last administration. CK-MB assay kit was adopted to detect the activity of serum CK-MB. HPLC was used to determine ATP, ADP and AMP contents in myocardial tissues and calculate TAN and EC.

RESULTThe preventive administration with SSNX could reduce the activity of serum CK-MB and increase ATP content and EC level in myocardial tissues (P < 0.01 or P < 0.05 vs. the model group).

CONCLUSIONSSNX formula can maintain energy charge in cardiomyocytes and relieve ischemia/reperfusion injury by preserving ischemic myocardium ATP.

Adenosine Diphosphate ; metabolism ; Adenosine Monophosphate ; metabolism ; Animals ; Creatine Kinase, MB Form ; blood ; Drugs, Chinese Herbal ; administration & dosage ; Energy Metabolism ; drug effects ; Humans ; Male ; Myocardial Ischemia ; drug therapy ; metabolism ; surgery ; Myocardial Reperfusion ; Rats ; Rats, Wistar

OBJECTIVETo observe the protective effects of paeonol, paeoniflorin, and their compatibility on in vitro cultured cardiomyocytes suffering from hypoxia-reoxygenation injury.

METHODSCardiomyocytes from neonatal rats were in vitro cultured and injured by a hypoxia of 2.5 - 5 h and a following 2-h reoxygenation. To observe the effects of paeonol and paeoniflorin, four doses of 100, 75, 50 and 25 mg/L were respectively set up. And to observe the compatibility of paeonol and paeoniflorin, five doses were set up as follows: paeonol 40 and 20 mg/L, paeoniflorin 40 and 20 mg/L, compatibility of paeonol 20 mg/L and paeoniflorin 20 mg/L. The above drugs were incubated with cardiomyocytes during the hypoxia and reoxygenation period respectively. No drug intervention was given to the model group, while no modeling was given to the normal control group. The transudatory creatine kinase (CK), lactate dehydrogenase (LDH), and malondialdehyde (MDA) in the culture medium were determined after the hypoxia period and the reoxygenation period respectively, and the total outleakage and the leakage inhibition ratio during the whole procedure were calculated. Results of each group were got from parallel operations for 5 times.

RESULTSCompared with the normal control group, the MDA leakage increased 2.5 h after hypoxia, the leakage and the total outleakage of CK, LDH, and MDA all significantly increased 3 and 5 h after hypoxia, and 2 h after reoxygenation. The leakage inhibition ratio of each index decreased with statistical difference (P<0.01, P<0.05). Compared with the model group, the leakage and the total outleakage of LDH and MDA both decreased in the high dose paeonol group, and the high and middle dose paeoniflorin groups after hypoxia and 2 h after reoxygenation (P<0.01, P<0.05), and the leakage inhibition ratio of each index increased (P<0.01, P<0.05). However, the leakage and the total outleakage of CK decreased in the low dose and the extreme low dose paeonol groups only 2 h after reoxygenation (P<0.01, P<0.05), while the leakage inhibition ratio of CK increased (P<0.01). The leakage and the total outleakage of LDH decreased in the extreme low dose paeoniflorin group only 2 h after reoxygenation (P<0.01), while the leakage inhibition ratio of LDH increased (P<0.01). The effects of their compatibility showed no significant difference (P>0.05).

CONCLUSIONSPaeonol, paeoniflorin, and their compatibility all have remarkable protective effects on in vitro cultured cardiomyocytes suffering from hypoxia-reoxygenation injury. There was no significant synergistic effect when paeonol was used with paeoniflorin together.

Acetophenones ; administration & dosage ; pharmacology ; Animals ; Animals, Newborn ; Benzoates ; administration & dosage ; pharmacology ; Bridged-Ring Compounds ; administration & dosage ; pharmacology ; Cell Hypoxia ; Cells, Cultured ; Creatine Kinase ; metabolism ; Glucosides ; administration & dosage ; pharmacology ; L-Lactate Dehydrogenase ; metabolism ; Malondialdehyde ; metabolism ; Monoterpenes ; Myocardial Reperfusion Injury ; metabolism ; Myocytes, Cardiac ; drug effects ; metabolism ; Rats