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 investigate the extent intravenously transplantation of mesenchymal stem cells (MSCs) mediated by magnetic targeting material arrive in the myocardial infarction region and its effects on the recovery of myocardial infarction. Methods Identify the phenotype of the fourth genet of ex vivo expanded MSCs, stain with DAPI after inducing with 10μmol/L 5-aza, then preserve the MSCs for transplantation. 28 SD rats were divided into three groups: group A (n=10), delivered MSCs combined with magnetic targeting material for 30 minutes to rats through tail vein,and kept on raising after placing magnets on the corresponding skin region to myocardial infarction area for 30min; group B (n=9), administration MSCs not conjuncted with magnetic targeting material through tail vein; group C (n=9), direct intramyocardial transplantation of MSCs. Two days after transplantation, evaluate the aggregation state of MSCs in the area of myocardial infarction; 30d later, estimate the functional and morphological changes in myocardial infarction region. Results We observed that each MSCs had 3-5 molecules of magnetic targeting material attached to its membrane under transmission electron microscope. The homing rates of MSCs respectively were group A 38%, group B 6%, group C 53%.The number of aggregating MSCs of group A and group C was apparently more than that of group B（Plt;0.01）. After transplantation, the contraction indices of left ventricle in group A and group C had significant improvement as compared with that of pretransplantation (LVEF 46%±6% vs. 38%±8%, 51%±5% vs. 35%±4%; LVFS 28%±6% vs. 20%±7%, 32%±4% vs. 20%±5%, Plt;0.05) and administrated cells stained with DAPI could be detected in infarction region under optical microscope. After transplantation, the contraction indices of left ventricle in group B hadn’t conspicuous improvement, and the transplanted cells labeled with DAPI could not be identified in infarction region under optical microscope (homing rate of MSCs 38%). There was no statistically difference of results between group A and group C, but in experiment process, there was a high mortality in group C. Conclusion The method that intravenously delivery of MSCs mediated by magnetic targeting material could accumulate much more MSCs in infarction region, reduce infarction size, and effectively improve the cardiac function after infarction.
An 84-year-old severe aortic stenosis patient admitted with acute heart failure was reported. Transcatheter aortic valve replacement (TAVR) was proposed. The patient was at high risk of the left coronary artery occlusion in preoperative and intraoperative evaluation. Coronary artery protection was performed by pre-embedded coronary artery guide wire and stent during the TAVR. The left coronary artery was partially blocked by valve leaflet after 23 mm self-expanding aortic valve was released. Coronary revascularization was not performed as the coronary blood flow was not affected. However, the patient suffered acute myocardial infarction with hypotension on the third day after TAVR. Emergency angiography showed that left coronary artery was more blocked than before and the condition improved after left main coronary stent implantation. This case suggested that aggressive coronary revascularization should be considered for high risk of coronary artery obstruction during TAVR, especially for partial obstruction of coronary artery.
Magneticaly labeled stem cells and magnetic resonance imaging(MRI) technology is an effective tracking method in vivo study, which has high spatial-temporal resolution. Gadolinium, which shows positive T1 signals and iron oxide showing negative T2 signals are the two often used contrast agents. The latter also include superparamagnetic iron oxide particle and ultrasmall superparamagnetic iron oxide particle. Transfection agents, e.g. poly-L-lysine and protamine sulfate，can enhance magnetical nanoparticles labeling stem cells. The biological characteristics of labeled stem cells did not seem to be altered. MRI can detect the labeled stem cells’ signals and also can track changes of signal in intensity and size with time past. In conclusion, MRI tracking magneticaly labeled stem cells represents a method for noninvasivly monitoring the existence and migration of engrafts.
Objective To investigate the effect of bone marrow mesenchymal stem cell (MSCs) transp1antation combined with transmyocardial drilling revascularization (TMDR) and degradable stent on myocardium revascu1arization after acute myocardial infarction(AMI), and to provide the experimental evidence for surgical treatment of myocardial infarction. Methods After established models of AMI, the 24 pigs were divided into four groups with random number table, 6 pigs each group. Control group: only established models of AMI; MSCs group: AMI immediately followed by MSCs implantation; TMDR combined with stent group: AMI followed by TMDR and absorbable basic fibroblast growth factor (bFGF) stent implantation; MSCs combined with TMDR and stent group: AMI followed by TMDR and absorbable bFGF stent implantation, and then MSCs implantation. Three months after operation, the infarcted areas and vessel density in infarcted zone were detected by histopathology method. Results Three months after operation, the histopathological examination showed that infarcted areas in MSCs group, TMDR combined with stent group, and MSCs combined with TMDR and stent group were decreased as compared with control group （27.9%±3.1% vs. 48.9%±2.7%，P=0.000；20.3%±1.7% vs. 48.9%±2.7%，P=0.000；12.5%±1.9% vs. 48.9%±2.7%，P=0.000）; and vessel density was further increased （8.4±1.2/HP vs.4.5±14/HP，P=CM(1583mm] 0.001；11.5±2.6/HP vs.4.5±1.4/HP，P=0.001;15.6±1.4/HP vs.4.5±1.4/HP，P=0.000）. Conclusion [CM)]MSCs transplantation combined with TMDR and absorbable bFGF stents implantation could significantly reduce the infarction areas, increase the vessel density. This method may enhance the efficacy of MSCs transplantation in acute cardiac infarction model, which provide a new ideas for the surgical treatment of myocardial infarction.
Ischemic mitral regurgitation is the common complication after myocardial infarction. Ischemic mitral regurgitation which can be described as the modification of the ventricle caused by myocardial infarction remarkably increases the risk of developing congestive heart failure and mortality after myocardial infarction. The imbalanced dynamic of tethering and occluding of the leaflets or the annular dilatation can result in ischemic mitral regurgitation. We have to diagnose, evaluate ischemic mitral regurgitation timely and perform surgical treatment effectively. It has significant meaning to improve the prognosis of patients.