Animals ; Cardiovascular Diseases ; drug therapy ; etiology ; Creatine Kinase, MB Form ; blood ; Heart ; drug effects ; Interleukin-1 ; blood ; Interleukin-6 ; blood ; Lycium ; chemistry ; Male ; Nitrates ; blood ; Oxidative Stress ; drug effects ; Physical Conditioning, Animal ; adverse effects ; Plant Extracts ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; blood

BACKGROUND: The early identification of heart failure (HF) risk may favorably affect outcomes, and the combination of multiple biomarkers may provide a more comprehensive and valuable means for improving the risk of stratification. This study was conducted to assess the importance of individual cardiac biomarkers creatine kinase MB isoenzyme (CK-MB), B-type natriuretic peptide (BNP), galectin-3 (Gal-3) and soluble suppression of tumorigenicity-2 (sST2) for HF diagnosis, and the predictive performance of the combination of these four biomarkers was analyzed using random forest algorithms. METHODS: A total of 193 participants (80 patients with HF and 113 age- and gender-matched healthy controls) were included from June 2017 to December 2017. The correlation and regression analysis were conducted between cardiac biomarkers and echocardiographic parameters. The accuracy and importance of these predictor variables were assessed using random forest algorithms. RESULTS: Patients with HF exhibited significantly higher levels of CK-MB, BNP, Gal-3, and sST2. BNP exhibited a good independent predictive capacity for HF (AUC 0.956). However, CK-MB, sST2, and Gal-3 exhibited a modest diagnostic performance for HF, with an AUC of 0.709, 0.711, and 0.777, respectively. BNP was the most important variable, with a remarkably higher mean decrease accuracy and Gini. Furthermore, there was a general increase in predictive performance using the multi-marker model, and the sensitivity, specificity was 91.5% and 96.7%, respectively. CONCLUSION The random forest algorithm provides a robust method to assess the accuracy and importance of predictor variables. The combination of CK-MB, BNP, Gal-3, and sST2 achieves improvement in prediction accuracy for HF.
Adult ; Algorithms ; Biomarkers ; blood ; metabolism ; Creatine Kinase, MB Form ; blood ; metabolism ; Echocardiography ; Female ; Galectin 3 ; blood ; metabolism ; Heart Failure ; blood ; metabolism ; pathology ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; metabolism

OBJECTIVE: To investigate the effects of excessive endoplasmic reticulum stress on lung ischemia/reperfusion (I/R) induced myocardial injury in mice. METHODS: Forty healthy SPF male C57BL/6J mice were divided into 4 groups randomly (=10):sham operation group (Sham group), lung I/R group (I/R group), endoplasmic reticulum stress (ERS) pathway agonist Tunicamycin group (TM) and ERS inhibitor 4-phenyl butyric acid group (4-PBA). The model of lung I/R injury was established by clamping the left hilum of lung for 30 min followed by 180 min of reperfusion. In sham group, only sternotomy was performed, the hilum of lung was not clamped, and the mice were mechanically ventilated for 210 min. In TM and 4-PBA groups, TM 1mg/kg and 4-PBA 400 mg/kg were injected intraperitoneally, respectively, at 30 min before establishment of the model. At 180 min of reperfusion, blood samples were collected from the orbit for determination of myocardial enzyme. The animals were then sacrificed, and hearts were removed for determination of light microscope, TUNEL, Caspase 3 enzymatic activity, real-time polymerase chain reaction and Western blot. RESULTS: Compared with sham group, the cardiomyocytes had obvious damage under light microscope, and the serum creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-Jun N-terminalkinase(p-JNK), Caspase 12, CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose regulated protein 78(GRP78) protein and mRNA were up-regulated in I/R, TM and 4-PBA groups (<0.01). Compared with I/R group, the cardiomyocytes damage was obvious under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-JNK, Caspase 12, CHOP and GRP78 protein and mRNA were up-regulated in group TM; while all above changes were relieved in group 4-PBA (<0.01). Compared with TM group, the cardiomyocytes damage was relieved under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were decreased significantly, the expressions of p-JNK, Caspase 12,CHOP and GRP78 protein and mRNA were down-regulated in group 4-PBA. CONCLUSIONS The excessive endoplasmic reticulum stress participates in myocardial injury induced by lung ischemia/reperfusion (I/R) and inhibit excessive endoplasmic reticulum stress response can relieved myocardial injury.
Animals ; Apoptosis ; Caspase 12 ; Caspase 3 ; metabolism ; Creatine Kinase, MB Form ; blood ; Endoplasmic Reticulum Stress ; Heart Injuries ; physiopathology ; Heat-Shock Proteins ; metabolism ; L-Lactate Dehydrogenase ; blood ; Lung ; pathology ; MAP Kinase Kinase 4 ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Myocardium ; pathology ; Random Allocation ; Reperfusion Injury ; Transcription Factor CHOP ; metabolism

To investigate the spectrum-activity relationship of Trichosanthis Fructus and Trichosanthis Fructus strip pieces for rat myocardial ischemia-reperfusion injury. HPLC fingerprints of Trichosanthis Fructus and Trichosanthis Fructus strip pieces were established, and the values of creatinekinase-MB (CK-MB), myoglobin (MYO) and cardiac troponin-T (cTNT) in 3 dose groups (2.25, 13.5, 27.0 g·kg⁻¹, equivalent to the crude herb g·kg⁻¹) of Trichosanthis Fructus and Trichosanthis Fructus strip pieces with myocardial ischemia-reperfusion injury in rats were measured, and the grey relational analysis was used to study the spectrum-activity relationship of Trichosanthis Fructus and Trichosanthis Fructus strip pieces for rat myocardial ischemia-reperfusion injury. With the dosage increase from 2.25 g·kg⁻¹ to 27.0 g·kg⁻¹, the correlation degree of spectrum-activity relationship of Trichosanthis Fructus and Trichosanthis Fructus strip pieces was also enhanced, but the change trend was different between these two groups. According to the frequency of the top 10 peaks in the correlation degree, peak 17, 14, 16, 19, 32, 12, 26, 30, 4, 6 and 2 were the basic effective substances group of Trichosanthis Fructus, peak 6,14,12,32,30,4 and 6 were the basic effective substances group of Trichosanthis Fructus strip pieces. Peak 6, 14, 12, 32, 30, 4 and 26 in fingerprints of Trichosanthis Fructus and Trichosanthis Fructus strip pieces were the main common pharmacodynamic substance base, among them, peak 6 was 5-hydroxymethyl furfural, peak 14 was vanillic acid and the peak 28 was rutin, but the correlation degree with the efficacy was different. The effect of Trichosanthis Fructus and Trichosanthis Fructus strip pieces on rat myocardial ischemia-reperfusion injury was due to the synergistic effect of the effective substance groups related to the dosage. The essential pharmacodynamic substance groups of Trichosanthis Fructus and Trichosanthis Fructus strip pieces were different, but they shared a common active ingredient group.
Animals ; Chromatography, High Pressure Liquid ; Creatine Kinase, MB Form ; blood ; Cucurbitaceae ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Fruit ; chemistry ; Myocardial Reperfusion Injury ; drug therapy ; Myoglobin ; blood ; Rats ; Troponin T ; blood

OBJECTIVE: To compare the changes in muscle enzyme between children with myocarditis and Duchene/Becker muscular dystrophy (DMD/BMD), and to seek the explanations for variation.
 METHODS: The retrospective analysis for 83 myocarditis children (myocarditis group) and 69 DMD/BMD children (DMD/BMD group), who were collected from Department of Pediatric of Shengjing Hospital affiliated to China Medical University since January 2008 to May 2015, was carried out. At the same time, 24 healthy children from the Department of Pediatric Development served as a control group. The examination indexes included creatine kinase (CK), creatine kinase-isoenzyme MB (CK-MB), creatine kinase isoenzyme MB mass (CK-MB mass), cardiac troponin I (cTnI) and high-sensitive-cTnT (hs-cTnT).
 RESULTS: 1) In the myocarditis group, the CK increased from 100 to 1 000 U/L, reached a peak after 5 days, which lasted for a week and then dropped to the normal; the CK-MB reached a peak after 5 to 7 days and dropped to the normal a month later; the CK-MB mass reached a peak on the first day and dropped to the normal after 3 weeks; the cTn reached to a peak after 5 days and dropped to the normal after about 17 days; hs-cTnT reached to a peak on the first day and dropped to the normal after about 19 days. 2) In the DMD/BMD group, the CK increased significantly and 27 cases had a CK value of more than 10 000 U/L. After the treatment for 1 to 2 weeks, their enzyme rose again after a slight drop. In terms of cTnI, 6 cases showed a moderate increase, 5 of them couldn't drop to the normal level until more than 3 weeks later; the hs-cTnT increased in the 45 cases, which lasted for more than 3 weeks in the 31 cases of them and showed a tendency of persisting increase.
 CONCLUSION The cTnI and hs-cTnT rise significantly and possess wider observation window than CK and CK-MB mass in myocarditis children, with more sensitive and specific changes. The myocardial damage can occur before myasthenia and keep this trend for a long time in the DMD/BMD children. The trend of cTnI change in myocarditis children is similar to hs-cTnT, while hs-cTnT in DMD/BMD children is more sensitive than cTnI.
Biomarkers ; Child ; China ; Creatine Kinase ; blood ; metabolism ; Creatine Kinase, MB Form ; blood ; metabolism ; Female ; Humans ; Male ; Muscle Weakness ; enzymology ; Muscular Dystrophy, Duchenne ; enzymology ; therapy ; Myocarditis ; enzymology ; therapy ; Retrospective Studies ; Time Factors ; Troponin I ; blood ; metabolism ; Troponin T ; blood ; metabolism

OBJECTIVE: To investigate the effect of hydrogen sulfide (H2S) on cardiac myosin light chain kinase (MLCK) expression in diabetic rats.
 METHODS: A total of 32 male SD rats were randomly divided into a normal control group (NC group), a diabetic control group (DM), a NaHS treatment group (DM+NaHS) and a NaHS group (NaHS) (n=8 in each group). Intraperitoneal injection of streptozotocin was utilized to establish Type 1 diabetic rat model. The diabetic rats in the DM+NaHS and NaHS groups were intraperitoneally injected with 28 μmol/kg NaHS solution. Eight weeks later, the ventricular hemodynamic parameters, the ratio of heart weight/body weight (HW/BW ratio), the levels of lactate dehydrogenase (LDH) and creatine kinase MB isozyme (CK-MB) in serum were determined. The ultrastructures of myocardium were observed under electron microscopy. The expressions of MLCK mRNA and protein level in myocardium were detected by RT-PCR and Western blot, respectively.
 RESULTS: Compared with the NC group, there was no significant difference in the various indexes in the NaHS group (all P>0.05). The function of left ventricular contract and relaxation were decreased obviously in diabetic rats, while the HW/BW ratio was increased (all P<0.01). The levels of LDH and CK-MB were increased (both P<0.01) in serum, while the levels of MLCK mRNA and protein were decreased significantly (both P<0.01) in myocardial tissues. Compared with the DM group, the left ventricular hemodynamic parameters and myocardial ultrastructure damage were improved in the DM+NaHS group, while the HW/BW ratio was decreased (all P<0.05). The levels of LDH and CK-MB were decreased (both P<0.01), while the levels of MLCK mRNA and protein were increased significantly (both P<0.01).
 CONCLUSION H2S can protect myocardium in diabetic rats, which may be associated with upregulation of cardiac MLCK.
Animals ; Cardiotonic Agents ; pharmacology ; Creatine Kinase, MB Form ; blood ; Diabetes Mellitus, Experimental ; drug therapy ; Heart ; drug effects ; Hemodynamics ; Hydrogen Sulfide ; pharmacology ; L-Lactate Dehydrogenase ; blood ; Male ; Myocardium ; ultrastructure ; Myosin-Light-Chain Kinase ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sulfides ; pharmacology ; Ventricular Function, Left ; drug effects

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 explore the protective effects of right coronary artery ischemic preconditioning and post-conditioning on myocardial ischemia reperfusion injury in rabbit heart.
 Methods: A total of 30 rabbits were randomly divided into 4 groups: a control group (n=7), an ischemia reperfusion group (IR group, n=8), an ischemic preconditioning group (IPC group, n=8) and an ischemic post-conditioning group (IPO group, n=7). Venous blood samples were taken at pre-operation, 1 and 6 h post-operation, and the concentration of serum creatine kinase isoenzyme (CK-MB) and cardiac troponin-T (cTn-T) were measured. The infarct area of cardiac muscle was calculated.
 Results: Compared with the IR group, the levels of CK-MB and cTn-T at 1 and 6 h post-operation in the IPC group and the IPO group were reduced (all P<0.05). Compared with the IR group, the infarct size in the IPC group and the IPO group was significantly decreased, with significant difference (both P<0.05) .
 Conclusion: Right coronary artery ischemic preconditioning and post-conditioning exert significant protective effects on the myocardial ischemia reperfusion injury in New Zealand rabbits.
Animals ; Coronary Vessels ; Creatine Kinase, MB Form ; blood ; Heart ; Ischemia ; Ischemic Postconditioning ; Ischemic Preconditioning ; Ischemic Preconditioning, Myocardial ; Myocardial Infarction ; etiology ; pathology ; physiopathology ; prevention & control ; Myocardial Ischemia ; complications ; therapy ; Myocardial Reperfusion Injury ; prevention & control ; Myocardium ; Rabbits ; Troponin T ; blood

OBJECTIVETo observe the protective effects of histone deacetylase inhibitor on stress-induced myocardial injury.

METHODSHealthy male Wistar rats were randomly divided into 3 groups( n = 6), and the stress-induced myocardial injury model was established with chronic restraint stress method. The protective effects of histone deacetylase inhibitor on stress-induced myocardial injury were observed with Trichostatin A (TSA) intervention. Histone acetylation levels in myocardium of rats were detected by Western blot method, spectrophotometry method was used to dynamically determine the activity of rat serum lactate dehydrogenase (LDH), serum creatine kinase isoenzyme-MB (CK-MB) and Caspase 3, and nagar Olsen staining were used to observe the early myocardial damage.

RESULTSRestraint stress could significantly reduce the level of histone acetylation of myocardium in rats, and TSA intervention could inhibit the stress-induced reduction of myocardial levels of histone acetylation. Restraint stress could cause the significant increase of serum LDH activity ( P < 0.05), serum CK-MB activity ( P < 0.05), and the Caspase 3 activity of myocardial tissue (P < 0.05), and early myocardial damage also occurred during restraint stress. ISA intervention could significantly reduce the serum LDH activity (P < 0.05), the serum CK-MB activity (P < 0.05), the activity of myocardial tissue caspase 3 induced by restraint stress (P < 0.05), and the stress-induced myocardial injury was also attenuated by TSA intervention.

CONCLUSIONThe histone deacetylase inhibitor TSA can protect stress-induced myocardial injury.

Acetylation ; Animals ; Cardiotonic Agents ; pharmacology ; Caspase 3 ; blood ; Creatine Kinase, MB Form ; blood ; Histone Deacetylase Inhibitors ; pharmacology ; Hydroxamic Acids ; pharmacology ; L-Lactate Dehydrogenase ; blood ; Male ; Myocardium ; pathology ; Rats ; Rats, Wistar ; Restraint, Physical ; Stress, Physiological

OBJECTIVETo study the expression difference in MicroRNA-21 (miRNA-21) levels of the plasma between the patients with coronary heart disease and the subjects without coronary artery lesions, and its clinical significance.

METHODSPlasma was obtained from the patients with coronary heart disease(trial group,56 cases) and the subjects without coronary artery lesions(control group, 10 cases), patients with coronary disease were divided into angina(AP, 39 cases) and acute myocardial infarction(AMI, 17 cases)subgroup, the contents of miRNA-21 were detected using qRT-PCR method, and the differential expression of miRNA-21 in each group was analyzed. The levels of creatine kinase isoenzyme (CK-MB), high sensitive troponin I(cTnI), B type natriuretic peptide urea (BNP), Gensini, left ventricular ejection fraction (LVEF), integral value of coronary left ventricular end diastole diameter (LV) and homocysteine (HCY) were determined and the correlation between miRNA-21 and these clinical indexes was analyzed.

RESULTSCompared with control group, there was a significant difference in expression of miRNA-21 in patients with angina and AMI (P < 0.05), and miRNA-21 expression in AMI group was much higher than that in AP group. There was statistical significance in CK, CK-MB, cTnI, Genisis integral comparison between AMI group and control group (P < 0.05). The correlation analysis showed that there was a positive correlation between expression of CK, CK-MB, cTnI and the level of circulating miRNA-21 in patients with acute myocardial infarction. And there was a negative correlation between BNP, Gensini integral, LVEF value of coronary artery, LV and circulating miRNA-21.

CONCLUSIONmiRNA-21 was significantly elevated in acute myocardial infarction subgroup than the control group. The level of miRNA-21 associates with the degree of coronary artery stenosis, and might be a potential marker for the diagnosis of acute myocardial infarction. miRNA-21 may play an important role in protecting myocardium from ischemia/reperfusion injury.

Acute Disease ; Biomarkers ; blood ; Coronary Disease ; blood ; Creatine Kinase, MB Form ; metabolism ; Humans ; MicroRNAs ; blood ; Myocardial Infarction ; blood ; Natriuretic Peptide, Brain ; metabolism ; Troponin I ; metabolism