Objective To detect the bile acid profile in serum based on liquid chromatography-tandem mass spectrometry, and construct a combined biomarker diagnostic model for differentiating acute myocardial infarction (AMI) from unstable angina (UA). Methods A total of 180 patients with acute coronary syndrome who visited Huludao Central Hospital between August 2023 and February 2024 were randomly selected, and there were 117 patients with UA and 63 patients with AMI. Using liquid chromatography-tandem mass spectrometry, 15 bile acid subtypes in serum were detected. Orthogonal partial least squares discriminant analysis was used to compare the serum bile acid metabolic profiles of the subjects. Differences in metabolites were screened based on a significance level of P<0.05 and variable importance in projection (VIP)>1. Multiple logistic regression analysis was performed to construct a diagnostic model for differentiating AMI from UA, and the diagnostic performance of the model was evaluated using receiver operating characteristic (ROC) curve and other statistical methods. Results The differential bile acid biomarkers in the serum of UA and AMI patients included glycodeoxycholic acid, glycochenodeoxycholic acid (GCDCA), deoxycholic acid (DCA), glycocholic acid, and aurodeoxycholic acid (TDCA) (P<0.05, VIP>1). A binary logistic stepwise regression analysis showed that three bile acid biomarkers (GCDCA, DCA, and TDCA) and three common biochemical indicators (aspartate aminotransferase, creatine kinase, and total bile acid) were factors differentiating AMI from UA (P<0.05). The area under the ROC curve of the model was 0.986 [95% confidence interval (0.973, 0.999), P<0.001], demonstrating a good diagnostic performance. Conclusions GCDCA, DCA, and TDCA can serve as potential biomarkers for distinguishing AMI from UA. The model combining these three bile acids with aspartate aminotransferase, creatine kinase, and total bile acid can effectively identify AMI.
Objective To report an acute ischemic left ventricular heart failure model of safe, simple, relatively steady, and reproducible in sheep. Methods Fourteen female sheep with a body weight of 36.80±3.43kg were used in this study. Heart failure model was induced by partial occluding the middle left circumflex coronary artery （LCX） combined with pacemaker-induced tachycardia. Hemodynamic measurement was done before and after heart failure, myocardial examination was observed. Results Heart failure model was induced successfully in 10 sheep. Cardiac output dropped from 3.74±0.48L/min to 2.02±0. 51L/min （P〈0. 01）, mean arterial pressure decreased from 116. 10± 14.15 mmHg（1kPa = 7.5mmHg） to 68. 10± 14. 72mmHg （P〈0.01）, central venous pressure rose from 7. 10±2.18mmHg to 10. 70± 3.50 mmHg （P〈0.05）, right ventricular end-diastolic pressure increased from 6.10±3.57mmHg to 9.90±4.41mmHg（P〈0.05）, left atrial pressure increased from 8.10±2.13 mmHg to 12.00± 4.57mmHg （P〈0. 01 ）, and left ventricular end-diastolic pressure increased from 8. 50± 4. 17mmHg to 13.10± 10. 64mmHg（P〉 0. 05）. The myocardial ultrastructure injuries was marked. Conclusions Acute ischemic left ventricular heart failure could be induced by partial occlusion of the middle LCX combined with pacemaker-induced taehyeardia in sheep. This model is simple, easy to manipulate, relatively steady, and reproducible . It may be used for assessing cardiac assist devices.
Objective To report a reliable left heart failure model in sheep using selected ligation of the diagonal branch. Methods Four male sheep were used. After a left anterior thoracotomy in sheep, the diagonal branch of coronary artery was ligated at a point approximately 40% of the distance from the apex to the base of the heart. Hemodynamic and echocardiography measurements were done preligation, 30 minutes and 7 days after the coronary artery of diagonal branch ligation. The electrocardiograms were obtained as needed, and cardiac function was also evaluated. The sheep were killed for postmortem examination of their hearts. Results Four sheep survived the experimental procedures. Comparing with before surgery, systemic arterial blood pressure and cardiac output were decreased, pulmonaryartery systolic pressure, pulmonary capillary wedge pressure and central venous pressure were increased at 30 min and 7 days after selected ligation of the coronary artery of diagonal branch; left ventricular end-diastolic dimension and left ventricular end-systolic dimension were increased; left ventricular ejection fraction and left ventricular fractional shortening were also decreased (Plt;0.05). Conclusion A reliable ovine model of left ventricular failure using selected ligation of the diagonal branch of the coronary artery can be achieved. This animal model is comparable to the clinical correlation.
Objective To investigate the effects of granulocyto-colony stimulating factor (G-CSF) on the mobil ization of endothel ial progenitor cells (EPCs) in the rats with myocardial infarction (MI), to observe the density of neovascularization and the mRNA expressions of vascular endothel ial growth factor (VEGF) and its receptor (Flk-1) in the border area of MI. Methods Thirty-six adult male rats (weighing 250-280 g) were divided randomly into control group, MI group, and G-CSF group. In MI group and G-CSF group, the models of MI were establ ished by left anterior descenting coronary artery l igation and were treated with intraperitoneal injection of sal ine (0.3 mL/d) or G-CSF [30 μg/(kg•d)] for 5 days. In control group, after open chest operation, chest was closed without treatment. The level of EPCs was surveyed and the plasma concentrations of VEGF and C-reaction protein (CRP) were measured at 7 days. The mRNA expressions of VEGFand its receptor Flk-1 in the border area of infarct myocardium were determined through RT-PCR. Results Compared withcontrol group, the number of circulating white blood cell (WBC) and EPCs levels, and the serum concentrations of VEGF and CRP were all significantly increased in MI group and G-CSF group (P lt; 0.05); when compared with MI group, the number of circulating WBC and EPCs levels, and the serum concentrations of VEGF were increased and the concentration of CRP was decreased in G-CSF group (P lt; 0.05). Compared with control group, the mRNA expressions of VEGF and Flk-1, and the density of neovascularization in the border area of infarct myocardium were increased in MI group and G-CSF group, whereas those in G-CSF group were significantly augmented compared with MI group (P lt; 0.05). Conclusion In the rats with MI, G-CSF could promote EPCs mobil ization, increase the mRNA expressions of VEGF and Flk-1, and augment the density of neovascularization in the border area of infarct myocardium.
Objective To compare the diagnostic accuracy of different combination regimens of myocardial infarction markers in diagnosing acute myocardial infarction; and to estimate the effect of heart-type fatty acid-binding protein (H-FABP) in improving the diagnostic accuracy of the combinations. Methods Patients with acute onset of chest pain were included randomly. Serum concentrations of H-FABP and other biochemical markers for myocardial infarction (cTnI, Myo) were determined immediately, and then acute myocardial infarction (AMI) patients were defined according to the WHO criteria. ROC curves for three biochemical markers were established respectively, and the cutoff values of the three markers were determined accordingly. Three combination regimens of myocardial infarction markers for AMI diagnosis were designed: cTnI+Myo, cTnI+H-FABP, cTnI+H-FABP+Myo. Diagnostic accuracy of the three regimens were then calculated and compared. Results The AUCs for the three biochemical markers were AUCcTnI 0.938 (95%CI: 0.888-0.988), AUCMyo 0.743 (95%CI: 0.651-0.836), and AUCH-FABP 0.919 (95%CI: 0.873-0.964), respectively. AUCH-FABP was significantly larger than AUCMyo (Plt;0.01). The cutoff values of the three biochemical markers for diagnosing AMI were defined as CutoffcTnI 0.5 ng/mL, CutoffMyo 90 ng/mL, and CutoffH-FABP 5.7 ng/mL, respectively. The diagnostic accuracy of these markers and their combination regimens were calculated and presented as follows (cTnI, Myo, H-FABP, cTnI+Myo, cTnI+H-FABP, cTnI+Myo+H-FABP): sensitivity: 0.804, 0.674, 0.783, 0.957, 0.957 and 0.957; specificity: 0.966, 0.747, 0.954, 0.724, 0.92 and 0.724; diagnostic efficacy: 0.910, 0.722, 0.895, 0.805, 0.932 and 0.805, respectively. Compared with the combination of cTnI+H-FABP, the sensitivities of cTnI (Z=2.261, P=0.024), Myo (Z=3.497, Plt;0.001) and H-FABP (Z=2.478, P=0.013) were significantly lower; the specificities of Myo (Z=3.062, P=0.002), cTnI+Myo (Z=3.378, Plt;0.001) and cTnI+Myo+H-FABP (Z=3.378, Plt;0.001) were significantly lower; and the diagnostic efficacies of Myo (Z=4.528, Plt;0.001), cTnI+Myo (Z=3.064, P=0.002) and cTnI+Myo+H-FABP (Z=3.064, P=0.002) were significantly lower. Conclusion The combination regimen of cTnI+H-FABP which includes H-FABP as the sensitive marker seems to be more effective than the currently used combinations in diagnosing AMI in patients with acute onset of chest pain.
ObjectiveTo improve and assess the method of establishing myocardial infarction model in New Zealand rabbits. MethodsA total of 60 New Zealand rabbits were randomly divided into two groups:the left anterior descending coronary artery was ligated in a LAD group (n=30); the left circumflex coronary artery was ligated in a LC group (n=30). Electrocardiogram (ECG), ultrasound cardiogram (UCG), hemodynamics and histology procedures were performed to detect the changes of cardiac structure and function after myocardial infarction induced by LAD and LC ligation. ResultsSuccess rate of the LC group was significantly higher than that in the LAD group (P < 0.01), but the survival rate in the LC group was slightly lower than the LAD group (P < 0.05); ECG within 24 h and 1 week after surgery showed that the average values of ST segment elevation in the LC group were significantly higher than that in the LAD group (P < 0.05); UCG and hemodynamics results showed cardiac function in the LAD group did not decrease significantly (P > 0.05). In contrast, cardiac function in the LC group were significantly decreased (P < 0.05). Histopathologic analysis showed that the area of myocardial infarction in the LC group was significantly larger than that in the LAD group (P < 0.01). ConclusionThe myocardial infarction induced by the left circumflex coronary artery ligation is more consistent than that induced by the left anterior descending coronary artery ligation, suggesting that the former is a more appropriate experimental model for evaluations.
Objective To evaluate the effectiveness of nicorandil for reperfusion of acute myocardial infarction (AMI), so as to provide high quality evidence for formulating the rational AMI therapy. Methods Databases including The Cochrane Library (Issue 3, 2012), PubMed, EMbase, HighWire, CBM, and CNKI were searched to collect randomized controlled trials (RCTs) on nicorandil in AMI reperfusion published before March 2012. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and evaluated the methodological quality of the included studies. Then the meta-analysis was conducted using RevMan5.1 software. Results A total of 11 trials involving 1 027 patients were included. The results of meta-analyses showed that: for AMI reperfusion, nicorandil could decrease the non-reflow or slow flow rate (RR=0.34, 95%CI 0.19 to 0.61, P=0.000 3), improve the left ventricular ejection fraction (MD=5.49, 95%CI 4.51 to 6.47, Plt;0.000 01), reduce the left ventricular end-diastolic volume (MD=–14.38, 95%CI –17.31 to –11.45, Plt;0.000 01), and decrease the incidence of cardiac adverse events (RR=0.34, 95%CI 0.25 to 0.46, Plt;0.000 01), readmission rate (RR=0.33, 95%CI 0.17 to 0.63, P=0.000 8) and mortality rate (RR=0.40, 95%CI 0.16 to 0.97, P=0.04). Conclusion Current evidence shows that nicorandil used as an adjuvant for AMI reperfusion can increase coronary microcirculation, improve prognosis, and decrease the incidence of cardiac adverse events, readmission and mortality rate. Due to the limited quality and quantity of the included studies, this conclusion still needs to be further proved by performing more large-scale and high quality RCTs, so we suggest clinician should adopt rational therapies based on patient’s conditions.