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.
Abstract: Objective To observe the changes in morphology, structure, and ventricular function of infarct heart after bone marrow mononuclear cells (BMMNC) implantation. Methods Twenty-four dogs were divided into four groups with random number table, acute myocardial infarction (AM I) control group , AM I-BMMNC group , old myocardial infarct ion (OMI) control group and OM I-BMMNC group , 6 dogs each group. Autologous BMMNC were injected into infarct and peri-infarct myocardium fo r transplantation in AM I-BMMNC group and OM I-BMMNC group. The same volume of no-cells phosphate buffered solution (PBS) was injected into the myocardium in AM Icontrol group and OM I-control group. Before and at six weeks of cell t ransplantation, ult rasonic cardiography (UCG) were performed to observe the change of heart morphology and function, then the heart was harvested for morphological and histological study. Results U CG showed that left ventricular end diastolic dimension (LV EDD) , left ventricular end diastolic volume (LVEDV ) , the thickness of left ventricular postwall (LVPW ) in AM I-BMMNC group were significantly less than those in AM I-control group (32. 5±5. 1mm vs. 36. 6±3. 4mm , 46. 7±12. 1m l vs. 57. 5±10. 1m l, 6. 2±0. 6mm vs. 6. 9±0. 9mm; P lt; 0. 05). LVEDD, LVEDV , LVPW in OM I-BMMNC group were significantly less than those in OM I-control group (32. 8±4. 2 mm vs. 36. 8±4. 4mm , 48. 2±12. 9m l vs. 60.6±16.5m l, 7. 0±0. 4mm vs. 7. 3±0. 5mm; P lt; 0. 05). The value of eject fraction (EF) in OM I-BMMNC group were significantly higher than that in OM I-control group (53. 3% ±10. 3% vs. 44. 7%±10. 1% ). Compared with their control group in morphological measurement, the increase of infarct region thickness (7. 0 ± 1. 9mm vs. 5. 0 ±2.0mm , 6.0±0. 6mm vs. 4. 0±0. 5mm; P lt; 0. 05) and the reduction of infarct region length (25. 5±5. 2mm vs. 32. 1±612mm , 33. 6±5. 5mm vs. 39. 0±3. 2mm , P lt; 0. 05) were observed after transplantation in AM I-BMMNC group and OM I-BMMNC group, no ventricular aneurysm was found in AM I-BMMNC group, and the ratio between long axis and minor axis circumference of left ventricle increased in OM I-BMMNC group (0. 581±0. 013 vs. 0. 566±0.015; P lt; 0. 05). Both in AM I-BMMNC group and OM I-BMMNC group, fluorescence expressed in transplantation region was observed, the morphology of most nuclei with fluorescencew as irregular, and the differentiated cardiocyte with fluorescence was not found in myocardium after transplantation. The histological examination showed more neovascularization after transp lantation both in AMI and in OM I, and significant lymphocyte infiltration in AM I-BMMNC group. Conclusion BMMNC implantation into infarct myocardium both in AMI and OMI have a beneficial effect, which can attenuate deleterious ventricular remodeling in morphology and st ructure, and improve neovascularization in histology, and improve the heart function.
Abstract: Objective To evaluate the treatment efficacy of post-infarction left ventricular pseudo-aneurysm (LVPA) through surgical procedure, and explore the diagnosis and differential diagnosis details of LVPA. Methods Between May 1993 and July 2007, 7 cases were diagnosed through echocardiography aided with left ventriculography or multi-sliced computer tomography (MSCT) or magnetic resonance imaging (MRI); 6 cases with LVPA were surgically treated through different procedure that included direct closure, cut and patching or cut and sandwiching procedure choose according to its location, anatomical morphology, and comorbidity; accompanied diseases were treated by coronary artery bypass grafting(CABG) procedure. Results Six cases were diagnosed before surgery, and 1 case was diagnosed during the surgical procedure. One died from the cardiac tamponade due to rupture of LVPA before the surgical procedure, so the inhospital mortality was 14.3%（1/7）. There was no operative death. With the follow-up from 2 months to 13 years of the 6 operational survivors, 1 case died from cardiac rupture and pericardial tamponade 4 years after the repair procedure. Of the 5 surviving LVPA, the left ventricular ejection fraction(LVEF) values were from 43% to 52%, and 3 cases were in New York Heart Association (NYHA) class Ⅰ, and 2 cases were in NYHA class Ⅱ. Conclusion Echocardiography, aided with left ventriculography or MSCT or MRI, is an effective measure for diagnosis of LVPA. Surgical procedure is an effective measure to treat LVPA,but different surgical procedures, accompanied with homeochronous CABG procedure,should be adopted to deal with LVPA according its location, anatomical morphology, and accompanied deformity. The perioperative and mid-long term efficacy were good for the surgical treatment of LVPA, but it is imperative to pay attention to prevention of the recurrence and the late rupture of repaired LVPA.
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 identify clinical significance of high level cardiac troponin I （cTnI） in the early postoperative period of off-pump coronary artery bypass grafting （OPCAB） and its predictive value for early clinical outcomes. Methods A total of 240 patients undergoing isolated OPCAB in the Department of Cardiac Surgery of People’s Hospitalof Peking University during 2011 were recruited in the study. There were 164 males and 76 females with their age of 36-83（62.07±8.24） years. Serum cTnI levels in 4-6 hours and 12-18 hours after OPCAB were monitored. Influential factors and its predictive value for early clinical outcomes of OPCAB were analyzed. Binary logistic regression analysis，correlation analysis and receiver operating characteristic （ROC） curve were performed for statistic analysis. Results Serum cTnI level in 4-6 hours after OPCAB （TNI0） was 1.28±0.40 ng/ml，and serum cTnI level in 12-18 hours after OPCAB （TNI1） was 3.60±0.74 ng/ml. Binary logistic regression analysis revealed that graft number was significant influential factors of TNI0 （P=0.000） and TNI1 （P=0.010）. Serum cTnI level in 12-18 hours after OPCAB was significantly correlated with early clinicaloutcomes of OPCAB （P＜0.05），but the correlational relationship was not b （correlation coefficient＜0.5）. ROC curveanalysis showed that serum cTnI level in 12-18 h after OPCAB had higher predictive value for patient prognosis （P＜0.05）. Serum cTnI level higher than 1.49 ng/ml in 12-18 h after OPCAB had good predictive value for postoperative ECG changes，use of intra-aortic balloon pump （IABP） and in-hospital mortality. Conclusions Serum cTnI level increases in varying degrees in the early postoperative period of OPCAB. Together with ECG changes，serum cTnI level can be used for early diagnosis of perioperative myocardial infarction with significant predictive value for early clinical outcomes of OPCAB.
Abstract: Objective To investigate the effect of autologous bone marrow mesenchymal stem cells (MSCs) transplantation on cardiac function and their proliferation and differentiation in the post-infarct myocardium in rabbits. Methods Twenty New Zealand rabbits were randomly divided into two groups, the autologous bone marrow mesenchymal stem cells group (MSCs group,n=10) and control group (n=10). Myocardial infarct model was set up by ligation of the left anterior descending (LAD), two weeks after establishment of the infarct model,either 400μl of cell suspension (total cells 1×106) labled by 1,1’-dioctadecyl3,3,3’,3’-tetramethyl indocarbocyanine perchlorate (Dil) or a comparable volume of L-DMEM medium were autologously transplanted into several different points of the periphery of the scar respectively. To evaluate the heart function, echocardiography were performed before modeling,two weeks after modeling, 2 and 4 weeks after the cells transplantation for asurements of left ventricular end systolic diameter (LVESD) and left ventricular end diastolic diameter (LVEDD), tocalculate left ventricular eject fraction(LVEF) and left ventricular fractional shortening (LVFS). Meanwhile the myocardial contrast echocardiography (MCE) were performed for evaluating the blood perfusion of the post-infarct myocardium. Eight weeks after the transplantation, the animalswere undergoing euthanasia, specimens were acquired for pathology. Results Echocardiography indicated that:The LVEF and LVFS between two groups were fundamentally the same before modeling,two weeks after modeling respectively (0.72±0.08 vs. 0.71±0.04,0.56±0.11 vs. 0.55±0.09; 0.35±0.06 vs. 0.35±0.04, 0.24±0.08 vs. 0.23±0.03, Pgt;0.05), but those were improved significantly in group MSCs when compared with control group at two weeks and four weeks after the cells transplantation(0.71±0.05 vs. 0.60±0.05，0.72±0.07 vs. 0.62±0.08 and 0.34±0.03 vs. 0.29±0.01， 0.35±0.06 vs. 0.27±0.05 respectively,Plt;0.05). There were no differences in LVESD and LVEDD between two groups in any time points(Pgt;0.05). MCE showed the blood perfusion of the infarct myocardium were improved two and four weeks after the cell transplantation. Pathology indicated that Dil positive cells were survived in MSCs transplanted hearts, stained positively for αsarcomeric actin and desmin eight weeks after cell transplantation, HE slides indicated that the capillary density in all the cells transplanted hearts were much higher when compared with control group (38.6±7.6/mm2 vs. 21.4±3.9/mm2，Plt;0.05). ConclusionMSCs can differentiate into cardiomyocytes, improve myocardial perfusion and cardiac function when transplanted into ischemic myocardium.
Objective To investigate the influence of infarcted myocardial construction by umbilical cord blood mesenehymal stem cells（MSC） with induced to myo-derived stem cells and implanted into infarcted myocardium. Methods Thirty-six adult mongrel canines were randomly divided into MSC transplant group and control group （18 each group）. Transplant group： the umbilical cord blood MSC differented to myo-derived stem cells induced by 5-azacytidine（5-aza） were implanted into the acute myocardial infarct site via the ligated left anterior descending （LAD） artery. Control group： administer the same volume of IMDM culture medium containing 0. 02% 4,6- diamidino-2-phenylindone （DAPI）. At 2, 4, 8 weeks after implantation, the change of basic myocardial construction and the distribution of desmin were observed by using Nagar-Olsen staining and immunohistology respectively. Results With less fusing, the arrangement of gelatine fibers and elastic fibers were in order in transplant group,and they were partly fused in control group by Nagar-Olsen staining. The expression of desmin of infarcted myocardial cell in transplant group was much higher than those in control group （P〈0. 01）. No significant difference was detected in the expression of desmin in normal site of both groups （P〉0. 05）. Conclusion There is an protective effect on the basic myocardial construction in infarcted myocardium after the umbilical cord blood MSC was differented to myo-derived stem cell by induced with 5-aza in vitro and implanted into the acute myocardial infarction.
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.
Objective To summarize the surgical experiences of ventricular septal rupture (VSR) after acute myocardial infarction (AMI) and investigate the time and methods of surgery. Methods From January 1999 to December 2008, 22 patients with VSR after AMI underwent surgical procedures. There were 17 male and 5 female with a age of 3978 years (mean age of 61.77 years). There were 18 cases with anterior VSR and 4 cases with posterior VSR, all of them combined with left ventricular aneurysm. Twentytwo cases underwent ventricular septal repair and aneurysm resection, 16 cases underwent coronary artery bypass grafting concomitantly with a graft of 2.11±1.57. Results There were 2 perioperative deaths (9.09%), 1 died of severe low cardiac output syndrome and 1 died of massive cerebral embolism. The other 20 cases were all cured and discharged. According to cardiac function classification from New York Heart Association（NYHA）, there were 4 cases in grade Ⅲ, 12 cases in grade Ⅱ and 4 cases in grade Ⅰ. Echocardiography showed that there were no VSR shunt and 2 cases with mild mitral valve regurgitation. Postoperative left ventricular enddiastolic diameter (LVEDD) reduced significantly compared with that before operation (50.27±5.33 mm vs. 57.94±6.79 mm, t=4.437, P=0.000). Sixteen cases were followed up, and the follow-up time was 3.24 months (13.9±6.5 months). Four cases were lost. There was no late death and cardiovascular event during following up. There were 11 cases in cardiac function classification (NYHA) grade Ⅱ and 5 in grade Ⅰ. Echocardiography showed that LVEDD reduced significantly (49.50±4.66 mm vs. 57.94±6.79 mm, t=5.041, P=0.000) and left ventricular ejection fraction (LVEF) increased significantly (55.08%±6.72% vs. 45.57%±11.31%, t=2.719, P=0.013)compared with those before operation. Conclusion VSR after AMI is one of the serious complications of AMI. Proper operation timing, perfect preoperative preparation, appropriate perioperative treatment, right surgical method and the avoidance of complications can effectively reduce the mortality and improve the prognosis.