Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of Tanshinone IIA (TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein (CRP), procalcitonin (PCT), cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), and brain natriuretic peptide (BNP) in cecal ligation and puncture (CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and high mobility group protein B1 (HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose (15 mg·kg), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30% (P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.
Animals ; C-Reactive Protein ; genetics ; immunology ; Cecum ; surgery ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Female ; Heart ; drug effects ; physiopathology ; Humans ; Interleukin-6 ; genetics ; immunology ; Ligation ; adverse effects ; Male ; Myocardium ; immunology ; Phenanthrenes ; administration & dosage ; chemistry ; Punctures ; adverse effects ; Rats ; Salvia miltiorrhiza ; chemistry ; Sepsis ; drug therapy ; etiology ; immunology ; physiopathology ; Troponin T ; genetics ; immunology ; Tumor Necrosis Factor-alpha ; genetics ; immunology

OBJECTIVE: To investigate changes of cardiac and muscle damage markers in exercise-induced hypertension (EIH) runners before running (pre-race), immediately after completing a 100-km ultramarathon race, and during the recovery period (24, 72, and 120 hours post-race). METHODS: In this observational study, volunteers were divided into EIH group (n=11) whose maximum systolic blood pressure was ≥210 mmHg in graded exercise testing and normal exercise blood pressure response (NEBPR) group (n=11). Their blood samples were collected at pre-race, immediately after race, and at 24, 72, and 120 hours post-race. RESULTS: Creatine kinase (CK) and cardiac troponin I (cTnI) levels were significantly higher in EIH group than those in the NEBPR group immediately after race and at 24 hours post-race (all p < 0.05). However, lactate dehydrogenase (LDH), creatine kinase-myocardial band (CKMB), or CKMB/CK levels did not show any significant differences between the two groups in each period. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were significantly higher in EIH group than those in NEBPR group immediately after race and at 24 and 72 hours post-race (all p < 0.05). A high sensitivity C-reactive protein (hs-CRP) level was significantly higher in EIH group than that in NEBPR group at 24 hours post-race (p < 0.05). CONCLUSION: The phenomenon of higher inflammatory and cardiac marker levels in EIH group may exaggerate cardiac volume pressure and blood flow restrictions which in turn can result in cardiac muscle damage. Further prospective studies are needed to investigate the chronic effect of such phenomenon on the cardiovascular system in EIH runners.
Biomarkers* ; Blood Pressure ; C-Reactive Protein ; Cardiac Volume ; Cardiovascular System ; Continental Population Groups ; Creatine ; Creatine Kinase ; Exercise Test ; Humans ; Hypertension* ; L-Lactate Dehydrogenase ; Myocardium ; Observational Study* ; Prospective Studies ; Running* ; Troponin I ; Volunteers

PURPOSE: Changes in serum biomarkers of cardiac and muscle damage have been studied in ultra-marathon runners for distances up to 308 km. We investigated these biomarker changes following a 622-km super-ultramarathon race. METHODS: A group of men with a mean age of 52.7±4.8 years participated. Blood samples were obtained pre-race, during the race, and post-race, to analyze the aforementioned biomarkers. RESULTS: Creatine kinase and creatine kinase-MB (CK-MB) levels increased during the race, and both steadily declined post-race with CK-MB declining at a slower rate. Lactic acid dehydrogenase levels overall were increased over pre-race levels. White blood cell counts increased during the race. Red blood cell decreased from pre-race to 300 km and 622 km. Platelet increased only in the recovery period. High-sensitivity C-reactive protein levels were increased throughout the race and at day 3 compared to pre-race levels. Cardiac troponin I (cTnI) levels increased during the race. N-terminal pro b-type natriuretic peptide (NT-proBNP) levels increased during the race. CONCLUSION: The rise in cTnI was not clinically significant, and highly elevated NT-proBNP levels during the race indicates that myocardial burden rose linearly as running distance increased. However, no clinical risk was found as most of the markers returned to normal range during the recovery.
Biomarkers ; Blood Platelets ; C-Reactive Protein ; Continental Population Groups* ; Creatine ; Creatine Kinase ; Erythrocytes ; Humans ; Lactic Acid ; Leukocyte Count ; Male ; Natriuretic Peptide, Brain ; Oxidoreductases ; Reference Values ; Rhabdomyolysis ; Running ; Troponin I

PURPOSE: Recent reports showed that plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) could be a useful biomarker of intravenous immunoglobulin (IVIG) unresponsiveness and coronary artery lesion (CAL) development in Kawasaki disease (KD). The levels of these peptides are critically influenced by age; hence, the normal range and upper limits for infants and children are different. We performed an age-adjusted analysis of plasma NT-proBNP level to validate its clinical use in the diagnosis of KD. METHODS: The data of 131 patients with KD were retrospectively analyzed. The patients were divided into 2 groups—group I (high NT-proBNP group) and group II (normal NT-proBNP group)—comprising patients with NT-proBNP concentrations higher and lower than the 95th percentile of the reference value, respectively. We compared the laboratory data, responsiveness to IVIG, and the risk of CAL in both groups. RESULTS: Group I showed significantly higher white blood cell count, absolute neutrophil count, C-reactive protein level, aspartate aminotransferase level, and troponin-I level than group II (P<0.05). The risk of CAL was also significantly higher in group I (odds ratio, 5.78; P=0.012). IVIG unresponsiveness in group I was three times that in group II (odds ratio, 3.35; P=0.005). CONCLUSION: Age-adjusted analysis of plasma NT-proBNP level could be helpful in predicting IVIG unresponsiveness and risk of CAL development in patients with KD.
Aspartate Aminotransferases ; C-Reactive Protein ; Child ; Coronary Vessels ; Diagnosis ; Humans ; Immunoglobulins ; Immunoglobulins, Intravenous ; Infant ; Leukocyte Count ; Mucocutaneous Lymph Node Syndrome* ; Neutrophils ; Peptides ; Plasma* ; Reference Values ; Retrospective Studies ; Troponin I

OBJECTIVE: To investigate the usefulness of cardiac biomarkers in the evaluation of prognosis and cardiac involvement (CI) in patients with acute aortic syndrome (AAS). METHODS: A total of 260 AAS patients with the measurements of cardiac biomarkers were divided into 2 groups; the survived (n=215, 60.6±13.7 years, 110 males) vs the dead (n=45, 64.5±13.6 years, 19 males). N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac specific troponin-I (cTnI), C-reactive protein (CRP), creatinine kinase (CK), MB fraction of CK (CK-MB), and D-dimer were compared. RESULTS: NT-proBNP and D-dimer were significantly elevated in the dead group than in the survived group (3558.7±5497.2 vs 949.9±2307.3 pg/mL, p<0.001, 4.5±5.1 vs 2.0±3.2 ug/mL, p<0.001, respectively). CI was observed in 59 patients (22.7%), and NT-proBNP was significantly elevated in patients with CI than in patients without CI (2497.7±4671.3 vs 722.5±1489.1 pg/mL, p=0.034). In univariate analysis, Stanford type A, CI, NT-proBNP, and D-dimer were significantly associated with mortality, but NT-proBNP was the only significant independent predictor of mortality in multivariate analysis. By receiver operating characteristic curve analysis, the optimal cut-off value to predict mortality was 517.0 pg/mL for NT-proBNP (area under the curve 0.797, sensitivity 86.7%, specificity 71.7%). CONCLUSION: The elevation of cardiac biomarkers is not infrequent in patients with AAS. NT-proBNP is significantly associated with CI and is an independent predictor of mortality in patients with AAS. The measurement of NT-proBNP would be useful in the risk stratification of AAS.
Biomarkers* ; C-Reactive Protein ; Creatinine ; Humans ; Mortality ; Multivariate Analysis ; Phosphotransferases ; Prognosis* ; ROC Curve ; Sensitivity and Specificity ; Troponin I

OBJECTIVETo evaluate the predictive value of serum iron level for in-hospital acute heart failure (AHF) after acute ST-elevated myocardial infarction (STEMI).

METHODSThis retrospective study involved 287 patients with STEMI stratified by quartiles of admission serum iron concentration. The incidence of AHF was assessed by serum iron quartiles. We evaluated the association of serum iron levels with B-type natriuretic peptide (BNP), cardiac troponin I (cTnI), and high-sensitivity C-reactive protein (hs-CRP) levels on admission, and analyzed the correlation of serum iron levels with in-hospital AHF, death, and duration of hospital stay.

RESULTSThe average serum iron level on admission of the 287 STEMI patients was 10.20 µmol/L (6.90-14.40 µmol/L), and the quartiles (Q) of serum iron levels were ≤6.90 µmol/L (Q(1)), 6.91-10.19 µmol/L (Q(2)), 10.20-14.39 µmol/L (Q(3)), and ≥14.40 µmol/L (Q(4)). The incidences of in-hospital AHF from Q(1) to Q(4) were 79.5%, 64.3%, 50.0% and 45.9%, respectively (P<0.001). Univariate logistic regression analysis showed that low admission serum iron level (Q(1)) was an independent predictor for in-hospital AHF (OR=3.358, 95%CI 1.791- 6.294, P<0.001), and multivariate logistic regression analysis showed a similar result (OR=2.316, 95%CI 1.205-4.453, P=0.012).

CONCLUSIONSA lower admission serum iron level is an independent predictor of AHF in STEMI patients during hospitalization.

Acute Disease ; C-Reactive Protein ; analysis ; Heart Failure ; blood ; diagnosis ; Hospitalization ; Humans ; Incidence ; Iron ; blood ; Myocardial Infarction ; blood ; Natriuretic Peptide, Brain ; analysis ; Predictive Value of Tests ; Retrospective Studies ; Troponin I ; analysis

In order to construct and express human cardiac troponin C-linker-troponin I(P) [ cTnC-linker-TnI(P)] fusion protein, detect its activity and prepare lyophilized protein, we searched the CDs of human cTnC and cTnI from GenBank, synthesized cTnC and cTnI(30-110aa) into cloning vector by a short DNA sequence coding for 15 neutral amino acid residues. pCold I-cTnC-linker-TnI(P) was constructed and transformed into E. coli BL21(DE3). Then, cTnC-linker-TnI(P) fusion protein was induced by isopropyl-β-D-thiogalactopyranoside (IPTG). Soluable expression of cTnC-linker-TnI(P) in prokaryotic system was successfully obtained. The fusion protein was purified by Ni²⁺ Sepharose 6 Fast Flow affinity chromatography with over 95% purity and prepared into lyophilized protein. The activity of purified cTnC-linker-TnI(P) and its lyophilized protein were detected by Wondfo Finecare™ cTnI Test. Lyophilized protein of cTnC-linker-TnI(P) was stable for 10 or more days at 37 °C and 4 or more months at 25 °C and 4 °C. The expression system established in this research is feasible and efficient. Lyophilized protein is stable enough to be provided as biological raw materials for further research.
Escherichia coli ; Freeze Drying ; Humans ; Recombinant Fusion Proteins ; biosynthesis ; Troponin C ; biosynthesis ; Troponin I ; biosynthesis

BACKGROUND AND OBJECTIVES: Apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a multifunctional protein involved in the DNA base excision repair pathway, inflammation, angiogenesis, and survival pathways. We investigated serum APE1/Ref-1 in patients with coronary artery disease (CAD). SUBJECTS AND METHODS: Serum APE1/Ref-1 was measured with a sandwich enzyme-linked immunosorbent assay from 360 patients who received coronary angiograms. They were divided into two groups; a control (n=57) and a CAD group (n=303), the latter included angina (n=128) and myocardial infarction (MI, n=175). RESULTS: The levels of APE1/Ref-1 were higher in the CAD than the control (0.63+/-0.07 vs. 0.12+/-0.07 ng/100 microL, respectively; p<0.01). They were also higher in MI than angina (0.81+/-0.10 vs. 0.38+/-0.11 ng/100 microL, respectively; p<0.01) and different according to the thrombolysis in myocardial infarction (TIMI) flow (0.88+/-0.09 for TIMI flow 0, 1, 2 vs. 0.45+/-0.13 ng/100 microL for TIMI flow 3, p<0.01) in acute coronary syndrome. In correlation analysis, the levels of APE1/Ref-1 were positively correlated with Troponin I (r=0.222; p<0.0001) and N-terminal pro-B type natriuretic peptide (NT-proBNP, r=0.217; p<0.0001) but not high sensitivity to C-reactive protein. Also, they revealed a negative correlation with ejection fraction (EF, r=-0.221; p=0.002). However, there were no significant differences among the three groups, were divided by their levels of APE1/Ref-1, for major adverse cardiovascular events (death, recurrent MI, stroke, revascularization) (8.2 vs. 14.0 vs. 12.5%, p=ns). CONCLUSION: The levels of serum APE1/Ref-1 are elevated in CAD, and are higher in MI than in angina. They are correlated with Troponin I, NT-proBNP, and EF.
Acute Coronary Syndrome ; Biomarkers ; C-Reactive Protein ; Coronary Artery Disease* ; Coronary Vessels* ; DNA ; DNA Repair ; Enzyme-Linked Immunosorbent Assay ; Humans ; Inflammation ; Myocardial Infarction ; Stroke ; Troponin I

OBJECTIVETo study the value of Pentraxin 3 (PTX3) in diagnosing the severity and cardiovascular function of the critically ill children. Method A total of 178 patients who were older than 28 days, with acute infection of respiratory or neurological system, excluding chronic or special disease, and admitted to the pediatric intensive care unit (PICU) of Hunan Children's Hospital from October 1, 2013 to April 30, 2014 were enrolled, including 102 male cases and 76 female cases. The ages ranged from 1 month to 13 years and 1 month, 78 of them were less than 1 year old ; 58 cases were between 1 to 3 years old; 42 cases were above 3 years old; 101 cases were diagnosed as respiratory system diseases, 77 cases had nervous system diseases. PTX3 was detected with enzyme-linked immunosorbent assay (ELISA) within 1 d after enrollment, at 3 days and 7 days, meanwhile, troponin, myocardial enzyme, brain-type natriuretic peptide (BNP), C-reactive protein (CRP), plasma calcitonin (PCT) and WBC etc. Were measured. According to the plasma PTX3 value which were measured within 24 h after enrollment the patients were divided into three groups: mildly elevated group (< 44 µg/L) 41 cases; moderately elevated group (44 - < 132 µg/L) in 66 cases; severely elevated group 71 cases (132 µg/L or higher). Those 178 patients were divided into 3 groups according to the degree of infection: non-sepsis group (78 cases), sepsis group (70 cases), severe sepsis group (30 cases), and in each group, those with heart failure were respectively 19 cases, 28 cases, 17 cases. Analysis of the plasma PTX3 expression changes in different clinical manifestations, different condition, different degrees of organ damages and prognosis for the patient. The continuous variables were analyzed with t-test, F-test, H-test, the categorical variables were analyzed with Chi-square test, and the correlation analysis was performed to calculate Pearson coefficients.

RESULTThe PTX3 value measured within 24 h after enrollment increased with the degree of infection (50. 4(35. 2,70. 4) µg/L; 175. 8 (99. 6, 309. 9) µg/L;419. 9 (168. 3, 468. 6) µg/L; H = 88. 345, P = 0. 000). PTX3 level gradually declined, while in severe sepsis group decreased slowly (P <0. 05); the area under the ROC curve of Plasma PTX3 was larger than that of other inflammatory markers such as CRP and PCT, white blood cells and neutrophils in the diagnosis of sepsis; while the former three are PTX3, PCT and CRP (the sensitivity and specificity respectively were 0. 77, 0. 68; 0. 66, 0. 6; 0. 47, 0. 55); the PTX3 value of the severely elevated group was significantly higher than those of the mildly and moderately elevated groups (P <0. 05). The proportion of having 3 or more organs failure increased as the PTX3 rising among the groups of mildly elevated group, moderately elevated group and severely elevated group (1(2. 4%), 4(6. 1%), 14(19. 7%) χ2 =16. 16,P = 0. 000); and in each group, the proportion of having good and poor prognosis for these three groups were different (33 (80.5%) and 8 (19. 5%), 35 (53%) and 31 (47%), 28 (39.4%) and 43 (60.6%), χ = 17. 663, P = 0. 000). The K-M curve for these three groups had statistically significant difference (χ2 = 7. 086, P = 0. 029). Those with heart failure had higher PTX3 value than those in non-heart failure at the same degree of infection. PTX3 value increased with myocardial enzyme (troponin, creatine kinase isoenzyme, BNP) levels. In the diagnosis of heart failure, the area under the ROC curve were respectively PTX3 0. 824; BNP 0. 772; CM-KB 0. 643; CNTIO. 671, the sensitivity and specificity were PTX3 0. 8, 0. 58; CK-MB 0. 56,0. 79; CTNI 0. 60,0. 69; BNP 0. 73, 0. 58. In terms of predicting the prognosis of sepsis with heart failure complications, the PTX3 value's area under ROC curve was larger than that of BNP (respectively 0. 844, 0. 472).

CONCLUSIONThe PTX3 is an objective biochemical marker in diagnosis of sepsis; it is helpful in assessment of severity and prognosis of sepsis; it also has a certain clinical value in the assessment of sepsis cardiovascular function damage.

Adolescent ; Biomarkers ; blood ; C-Reactive Protein ; analysis ; Calcitonin ; blood ; Cardiovascular System ; physiopathology ; Child ; Child, Preschool ; Creatine Kinase ; blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant ; Intensive Care Units, Pediatric ; Leukocyte Count ; Male ; Natriuretic Peptide, Brain ; blood ; Prognosis ; Protein Precursors ; blood ; ROC Curve ; Sensitivity and Specificity ; Sepsis ; diagnosis ; physiopathology ; Serum Amyloid P-Component ; analysis ; Troponin ; blood

BACKGROUNDPrevious studies have suggested that hypothyroidism correlated with coronary heart diseases (CHD) mortality in long-term cohort, but whether the thyroid function status is associated with myocardial injury in acute ST-elevation myocardial infarction (STEMI) has not been investigated sufficiently.

METHODSFive hundred and eighty-two hospitalized patients from January 2010 to December 2011, with the diagnosis of STEMI, were enrolled in this study. All patients underwent testing for thyroid function status, cardiac troponin I (cTnI), cardiac enzymes, C-reactive protein (CRP). We investigated the association between thyroid hormone levels and cardiac markers (creatine kinase-MB and cTnI), and thus evaluated the potential role of thyroid function status in predicting the myocardial injury.

RESULTSThere were 76 patients (13.06%) who had hypothyroidism including low-T3-syndrome (34 patients, 5.84%), subclinical hypothyroidism (28 patients, 4.81%) and clinical hypothyroidism (14 patients, 2.41%). After adjusting for conventional risk factors (age, gender, smoking, diabetes mellitus, dyslipidemia, hypertension), free triiodothyronine (FT3) was significantly and negatively correlated with log-CKMB (r = -0.244, P < 0.001) and log-cTnI (r = -0.290, P < 0.001), indicating that the lower thyroid hormone level correlates with the severer cardiac injury in STEMI patients. FT3 also had a moderate negative correlation with CRP (r = -0.475, P < 0.001), which might indicate that hypothyroidism may activate the inflammation response. No significant correlation was found between other thyroid parameters (TSH, FT4) and cardiac markers.

CONCLUSIONSAs the lower FT3 level correlates with higher level of cardiac markers and lower left ventricular ejection fraction (LVEF), the hypothyroidism may be a predictor for myocardial injury in STEMI. And these results may warrant further study to investigate whether reversing the hypothyroidism could benefit the STEMI patients.

Aged ; C-Reactive Protein ; metabolism ; Echocardiography ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; blood ; Myocardium ; metabolism ; pathology ; Thyroid Gland ; metabolism ; Triiodothyronine ; blood ; Troponin I ; metabolism