Effect of Intracoronary Infusion of Bone Marrow Mononuclear Cells or Peripheral Endothelial Progenitor Cells on Myocardial Ischemia-reperfusion Injury in Mini-swine

Objective To simulate and assess the clinical effect of intracoronary infusion of bone marrow mononuclear cells or peripheral endothelial progenitor cells on myocardial reperfusion injury in mini-swine model.Methods Twenty-three mini-swine with myocardial reperfusion injury were used as designed in the study protocol.About(3.54±0.90)×108 bone marrow mononuclear cells(MNC group,n=9) or(1.16± 1.07)×107 endothelial progenitor cells(EPC group,n=7) was infused into the affected coronary segment of the swine.The other mini-swine were infused with phosphate buffered saline as control(n=7).Echocardio-graphy and hemodynamic studies were performed before and 4 weeks after cell infusion.Myocardium infarction size was calculated.Stem cell differentiation was analyzed under a transmission electromicroscope.Results Left ventricular ejection fraction dropped by 0% in EPC group,2% in MNC group,and 10% in the control group 4 weeks after cell infusion,respectively(P<0.05).The systolic parameters increased in MNC and EPC groups but decreased in the control group.However,the diastolic parameters demonstrated no significant change in the three groups(P>0.05).EPC decreased total infarction size more than MNC did(1.60±0.26 cm2 vs.3.71±1.38 cm2,P<0.05).Undermature endothelial cells and myocytes were found under transmission electromicroscope.Conclusions Transplantation of either MNC or EPC may be beneficial to cardiac systolic function,but might not has obvious effect on diastolic function.Intracoronary infusion of EPC might be better than MNC in controlling infarction size.Both MNC and EPC may stimulate angiogenesis,inhibit fibrogenesis,and differentiate into myocardial cells.

IMPLANTATION OF AUTOLOGOUS BONE MARROW MONONUCLEAR CELLS INTO ISCHEMIC MYOCARDIUM ENHANCES CORONARY CAPILLARIES AND SYSTOLIC FUNCTION IN MINISWINE

Objective To investigate the therapeutic effectiveness of intracoronary implantation of autologous bone marrow mononuclear cells (BM-MNC) in miniswine model of reperfused myocardial infarction. Methods Sixteen miniswine myocardial ischemic reperfusion injury models made by ligation of the distal one third segment of left anterior descending artery for 90 minutes were randomized into 2 groups. In BM-MNC group (n = 9), (3.54±0.90)×108 BM-MNC were intracoronary injected, and in the control group (n = 7), phosphate buffered saline was injected by the same way. Echocardiographic and hemodynamic results, vessel density, and myocardial infarction size were evaluated and compared before and 4 weeks after cell transplantation. Results In BM-MNC group, there were no differences between before and 4 weeks after transplantation in aspects of left ventricular ejection fraction (LVEF), interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, or +dp/dtmax. In control group, LVEF, interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, and +dp/dtmax decreased significantly 4 weeks after transplantation (P < 0.05). Left ventricular end-diastolic pressure and –dp/dtmax did not change significantly before and after cell transplantation in both groups. Capillary density in BM-MNC group was greater than that in control group [(13.39 ± 6.96)/high power field vs. (3.50 ± 1.90)/high power field, P < 0.05]. Infarction area assessed by tetrazolium red staining and the infarction percentage decreased in BM-MNC group compared with those in control group (P < 0.05). Conclusions Transplantation of BM-MNC into myocardium with ischemic reperfusion injury increases capillary density and decreases infarction area. It has significantly beneficial effect on cardiac systolic function rather than on diastolic function.

N-terminal pro-B-type natriuretic peptide and diastolic function measurements by adenosine stress echocardiography in prediction of coronary stenosis in patients

Background Stress echocardiography is mainly used in detection of coronary artery disease （CAD） and to assess risk.This study aimed to use adenosine stress echocardiography （ASE） and N-terminal pro-B-type natriuretic peptide （NT-proBNP） to noninvasively assess coronary stenosis in patients with chest pain syndromes or anginal equivalent.Methods NT-proBNP was measured after overnight fast in fifty patients, 42 males and 8 females, who were （57＋11）years old. They then underwent echocardiography before and during adenosine administration. Left ventricular （LV）diastolic function analyzed included mitral annular early （E＇） and late velocity （A＇） both at the mitral septal and lateral level and the mitral inflow to annulus ratio （E/E＇）. Coronary angiography was performed the following day after which patients were assigned to three groups： normal results （16 patients）, stenosis 50%-69%（17 patients） and stenosis≥70% （17 patients）.Results NT-proBNP levels in the groups of stenosis 50%-69% and≥ 70% were significantly higher than that in the group with normal results （P=0.014 and P=0.040）. During adenosine stress, the E/E＇ in the group of stenosis≥70% was higher than in the group of normal results （P=0.024）. E＇lateral/A＇lateral in the group of stenosis 50%-69% and E＇septal/A＇septal and E＇lateral/A＇lateral in the group of stenosis≥70% were also decreased during stress compared with baseline （P=0.003,P=0.001, P=0.022）. The variation of E＇septal/A＇septal before and during adenosine stress （△E＇septal/A＇septal） between the groups of normal results and stenosis ≥70% were significantly different （P=0.001）. By receiver operating characteristic （ROC）, the specificity of △E＇septal/A＇septal ≥0.037 predicting coronary stenosis ＜70% was 94%. The sensitivity and specificity of NT-proBNP≥544.6 fmol/ml in predicting coronary stenosis ≥70% were 93% and 75%, respectively.NT-proBNP inversely correlated with E＇lateral/A＇lateral （r=-0.390, P=0.014） and positively correlated with E/E＇lateral（r=0.550,P=0.001）.Conclusions Adenosine might induce diastolic dysfunction in patients with coronary stenosis more than 70% and NT-proBNP could reflect LV diastolic function to a certain extent. We support the prediction that most patients having chest pain syndromes or anginal equivalent with NT-proBNP＜544.6 fmol/ml and in ASE AE＇septal/A＇septal≥0.037 might be spared coronary angiography.

ST-elevated acute myocardial infarction happening 1 month post stent implantation： late thrombosis in-stents or new lesions？

Background ST-elevated acute myocardial infarction （STEAMI） happening in the first month post percutaneous coronary intervention （PCI） is almost related to acute thrombosis or subacute thrombosis in-stents. This study aimed to investigate the possible causes of myocardial infarction one month later. Methods Patients who had a history of successful PCI, and received coronary angiography or re-PCI due to STEAMI were included in this study. The AMI-related lesions and previous angiographic findings such as the number of lesions, the degree of the stenosis, the type of stents and acute results of last PCI were recorded. If the AMI-related lesion was localized in-stents or at the edge of stents （distance apart from the edge 〈5 mm）, it was defined to be late thrombosis; otherwise as a new-lesion induced AMI. Results One hundred and ninety-two patients aged 40-79 years were included in this study. New lesions, as the cause of STEAMI, were found in 144 patients （Group A, 75%）, and late thrombosis in 48 patients （Group B, 25%）. Almost all newly built thromboses were found at the sites of previous insignificant lesions （diameter stenosis 〈50%）. There was a significant difference in the average time from previous PCI to AMI （（30.1±12.4） vs （20.3±11.9） months） between the two groups. Diabetes mellitus （DM） and drug-eluting stent （DES） utilization were associated with markedly higher morbidity of late thrombosis in adjusted Logistic regression （hazard ratio （HR） 3.4, 95% confidence interval （C/） 1.1-10.9 and 5.3, 95% Cl 1.1-26.5）. Conclusions STEAMIs happening 1 month after PCI are more likely to develop from previous insignificant lesion rupture than from late thrombosis in-stents. Moreover, DM and DES are associated with the high incidence of late thrombosis, which may indicate that intensive antiplatelet therapy should be considered in patients with diabetes.