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) x 10(8) bone marrow mononuclear cells (MNC group, n = 9) or (1.16 +/- 1.07) x 10(7) 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). Echocardiography 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.

Effects of intracoronary autologous bone marrow cells on left ventricular function in acute myocardial infarction: a systematic review and meta-analysis for randomized controlled trials.

BACKGROUND: Experimental and clinical studies have suggested that intracoronary infusion of bone marrow-derived stem/progenitor cells (BMC) may improve left ventricular function after acute myocardial infarction (AMI). We conducted a systematic review and meta-analysis to investigate the efficacy and safety of BMC therapy on global left ventricular function in AMI. METHODS: A systematic literature search of MEDLINE, Cochrane Controlled Trials Register, EMBASE, Science Citation Index, and PUBMED from their inception to March 2007 was conducted using specific search terms. Reference lists of papers and reviews on the topic were further searched. Finally, six randomized controlled trials that comprised 517 patients were eligible for further meta-analysis. We used a standardized protocol to extract information on the included studies. RESULTS: Compared with the control groups, BMC therapy produced a slight improvement of the follow-up left ventricular ejection fraction (LVEF) [2.53%, 95% confidence interval (CI): 0.67-4.39, P=0.008] between 3 and 6 months. Similarly, BMC therapy also significantly improved the LVEF change from baseline to follow-up [2.88%, 95%CI: 1.69-4.08, P=0.000] compared to control groups, and the heterogeneity across the studies with regards to the follow-up LVEF (P=0.696) and the LVEF change (P=0.179). Major adverse cardiovascular events, including ventricular arrhythmia, rehospitalization for heart failure, and the composite of other cardiovascular events (cardiac death, recurrent myocardial infarction, infarct-vessel revascularization procedure, and stroke), were not significantly different between BMC therapy and control groups [relative risk (RR): 1.19, 95%CI: 0.68-2.06; RR: 1.79, 95%CI: 0.62-5.17; and RR: 1.05, 95%CI: 0.81-1.35, respectively]. CONCLUSION: On the basis of present evidence, intracoronary BMC infusion in patients with AMI seems to be safe and associated with slight improvement of the left ventricular ejection fraction at 3-6 months' follow-up.

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) X 10(8) 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.

[Effect of intracoronary transplantation of autologous bone marrow mononuclear cells on myocardial ischemia reperfusion injury in mini-swine model].

OBJECTIVE: To investigate the therapeutic effectiveness of intracoronary transplantation of autologous bone marrow mononuclear cells (BM-MNC) on myocardial ischemia reperfusion injury in mini-swine model. METHODS: Myocardial ischemia reperfusion injury model was established by ligating in 16 mini-swines, which were further randomized into two groups: (3.54 +/- 0.90) x 10(8) BM-MNC was intracoronarily transplanted in BM-MNC group (n = 9), and phosphate buffer saline was intracoronarily applied in the control group (n = 7). Ultrasonic cardiograhpy, hemodynamics, neovascular density, and myocardium infarction size were evaluated before and 4 weeks after transplantation. RESULTS: In BM-MNC group, left ventricular ejection fraction (LVEF), intra-ventricular septa, lateral wall and anterior wall, cardiac output (CO) and + dp/dt(max) had no significant differences before and 4 weeks after transplantation (P > 0.05). In the control group, LVEF, intraventricular septa, lateral wall and anterior wall, CO, and + dp/dt(max) significantly decreased 4 weeks after transplantation (P < 0.05). Left ventricular end-diastolic pressure and- dp/dt(max) had no significant differences before and after cell transplantation. Capillary density was significantly larger in the BM-MNC group than in the control group [(13.39 +/- 6.96) /HP vs. (3.50 +/- 1.90) /HP]. The percentage and size of myocardial infarction was significantly lower in the BM-MNC group than in the control group. CONCLUSION: Transplantation of BM-MNC into the myocardial ischemic reperfusion-injury area can increase capillary density and decrease infarction area, and thus remarkably improve cardiac systolic function.

[Clinical features of unexpected sudden death clustered in 7 families in Yunnan Province].

OBJECTIVE: To investigate the clinical features of unexpected sudden death (SUD) clustered in families in Yunnan province. METHODS: This retrospective study analyzed the clinical features of SUD occurred between July to September 2005 in 7 families in Yunnan province. RESULTS: All 16 SUD patients shared common clinical features such as fatigue and repeated syncope and one group of SUD patients (n = 8 from 4 families) presented with the gastric intestinal tract manifestations including nausea, vomiting, abdominal pain and diarrhea with suspected dietary history and abnormal laboratory enzyme findings (GOT/GPT, CK/CKMB, LDH/LDH1 etc.). In SUD patients without gastric intestinal tract manifestations (n = 8 from 3 families), there were no clear symptoms before death and repeated ventricular tachycardia and ventricular fibrillation were recorded in one survivor. There was no clear evidence for the involvements of hereditary and infectious factors for observed SUD. CONCLUSION: The reason for the unexpected sudden death clustered in 7 families in Yunnan remains unclear. Repeated syncope and fatigue served as the common clinical features in the presence or absence of gastric intestinal tract manifestations in all SUD cases. Further studies are needed to clarify the pathology and detailed clinical manifestations of SUD occurred in this area.

Effectiveness and tolerability of administration of granulocyte colony-stimulating factor on left ventricular function in patients with myocardial infarction: a meta-analysis of randomized controlled trials.

BACKGROUND: Clinical studies suggest that granulocyte colony-stimulating factor (G-CSF)-mobilized stem cells are recruited to ischemic myocardium and differentiate into specialized cells such as cardiomyocytes, endothelial cells, and smooth muscle cells, and may improve left ventricular function. OBJECTIVES: The aim of this study was to investigate the effectiveness and tolerability of G-CSF treatment with regard to global left ventricular function in patients with myocardial infarction (MI). METHODS: A literature search was conducted of MEDLINE, Cochrane Controlled Trials Register, EMBASE, Science Citation Index, and PubMed (all from their inception to March 2007). Reference lists of papers and reviews on the topic were also searched. We selected the following criteria for trials included in this study: (1) randomized controlled trial (RCT) design of MI routine therapy comparing G-CSF with placebo or blank control in patients with MI; (2) > or =3 to < or =12 months' follow-up after G-CSF treatment; (3) diagnosis of acute MI (AMI) (< or =14 days from onset of new ST-segment elevation infarction) or old MI (OMI) (>14 days from onset); (4) complete left ventricular ejection fraction (LVEF) data and major adverse cardiovascular event (MACE) reports; and (5) the availability of demographic characteristics of patients and the duration and dose of G-CSF treatment. This information was independently extracted by 2 of the investigators using a standardized protocol. RESULTS: Of the 14 RCTs meeting the inclusion criteria, 7 RCTs were deemed eligible for further analysis. The remaining studies included 364 patients (G-CSF groups, 179; control groups, 185; mean age range, 49.8-63.0 years). A significant increase in follow-up LVEF (LVEF(follow-up)) was observed in the G-CSF groups compared with the control groups (2.96%; 95% CI, 0.98-4.94; P = 0.003), and the LVEF change from baseline to follow-up (LVEF(Delta)) also significantly increased (3.46%; 95% CI, 0.60-6.32; P = 0.018). The heterogeneity was significant across the studies with regard to LVEF(follow-up) (P = 0.068) and the LVEFA (P = 0.001). The relative risk (RR) for the prevalence of MACEs, including ventricular arrhythmia (RR, 0.65; 95% CI, 0.29-1.49), rehospitalization for heart failure (RR, 2.00; 95% CI, 0.36-11.17), and the composite of other cardiovascular events (ie, cardiac death, recurrent MI, infarct-vessel revascularization procedure, and stroke) (RR, 1.07; 95% CI, 0.71-1.60), was not significantly different in the G-CSF treatment groups compared with the control groups. The overall risk for MACE was also not significantly different between the 2 groups (RR, 0.93; 95% CI, 0.57-1.28). CONCLUSION: Based on the studies included in this meta-analysis, G-CSF treatment improved the LVEF in AMI (but not OMI) at 3 to 12 months follow-up. Treatment with G-CSF was generally well tolerated.

[Autologous bone marrow mononuclear cells and peripheral endothelial progenitor cells differentiation in myocardial ischemia reperfusion injury region in swine].

OBJECTIVE: To investigate the differentiation status of autologous bone marrow mononuclear cells (BM-MNC) and peripheral endothelial progenitor cells (EPC) transplanted into myocardial ischemia reperfusion injury region in swine. METHODS: BM-MNC marked with PKH26 (n = 9), EPC marked with CM-DiI (n = 7), phosphate buffer saline (control, n = 7) were transplanted into myocardial ischemia reperfusion injury region of swine by intracoronary artery injection. Specimens were harvested 4 weeks after injection for histological analysis (HE, immunochemical stain for vWF, alpha-sarcomeric-actin and fibronectin antibody). Cell differentiation was observed under transmission electronmicroscope. RESULTS: The number of small blood vessels was similar between BM-MNC group and EPC group (13.39 +/- 6.96/HP vs.12.39 +/- 4.72/HP, P < 0.05), but was significantly higher than that of control group (P < 0.05). Responsive intensity of immunochemical stain for fibronectin antibody was significantly lower in BM-MNC and EPC groups than that in control group. Responsive intensity of immunochemical stain for alpha-sarcomeric-actin antibody was similar among the three groups. Cluster cells were observed in one swine from BM-MNC group which might relate to the proliferation of stem cells in situ. Immature endothelial cells and myocytes were also detected by transmission electronmicroscope in BM-MNC and EPC group. CONCLUSION: BM-MNC and EPC transplanted into myocardial ischemia reperfusion injury region in swine stimulated the formation of blood vessels and inhibited fibrogenesis.

[Effects of intracoronary transplantation of autologous bone marrow mononuclear cells or endothelial progenitor cells in mini-swine model of myocardial ischemia-reperfusion].

OBJECTIVE: To compare the effects of intracoronary transplantation of autologous bone marrow mononuclear cells (BM-MNC) or peripheral endothelial progenitor cells (EPC) in mini-swine model of myocardial ischemia-reperfusion. METHODS: The Mini-swine acute myocardial infarction and reperfusion model was created with 90 min occlusion of the left anterior descending coronary artery followed by reperfusion and the animals were then divided into BM-MNC group (3.54 x 10(8) +/- 0.90 x 10(8), n = 9), EPC group (1.16 x 10(7) +/- 1.07 x 10(7), n = 7) and control group (saline, n = 7). Echocardiography, hemodynamic measurements and myocardium infarction size were evaluated before and 4 weeks after intracoronary cell transplantations. RESULTS: The net decrease from baseline to 4 weeks after transplantation of left ventricular ejection fraction (LVEF), left ventricular end systolic pressure, cardiac output and +dp/dt(max) were significantly attenuated post BM-MNC and EPC therapy compared to control group (all P < 0.05) and were similar between BM-MNC and EPC groups. Transplantation of BM-MNC and EPC also significantly decreased myocardial infarction size compared to control group. CONCLUSION: Autologous intracoronary transplantation of BM-MNC or EPC in this model equally improved cardiac systolic function and reduced infarction area.

[Electrocardiogram analysis in high risk population of unexplained sudden death in Yunnan province].

OBJECTIVE: The purpose of this study was to analyze the electrocardiographic features of the people living in the area with high incidence of unexplained sudden deaths in Yunnan province. METHOD: The electrocardiograms of 338 residents from three villages (Dayao, Ninglang, Heqing) with high incidence of unexplained sudden deaths and one control village (Dali) were analyzed [averaged age was (33.4 +/- 11.7) years, 175 men and 163 women]. RESULTS: The incidence of cardiac arrhythmias was similar low in all groups. The left ventricular hypertrophy was observed in 34.6% of residents from Dayao. QTc significantly prolonged in the residents from all 3 high incidence areas compare the control area of Dali [control (386.8 +/- 27.22) ms, Ninglang (428.92 +/- 25.71) ms, Heqing (440.67 +/- 28.03) ms, Dayao (417.7 +/- 24.00) ms, P < 0.05 vs. control]. Incidence of U wave was significantly higher in Heqing village than that in control village (P < 0.05). The QUc of these 3 villages was: (613.67 +/- 37.34) ms, (597.19 +/- 46.47) ms, (608.59 +/- 39.59) ms respectively, and also significantly longer than the control village of Dali (589.33 +/- 41.27) ms (P < 0.05). The typical pattern of U wave presents as enlarged U wave and apparent T-U complex. In the 7 residents who have the family history of unexplained sudden death, 6 residents have U wave, and 4 of them present typical U wave pattern. CONCLUSION: The significant ECG changes in villages with high incidence of unexplained sudden death in Yunnan province were prolonged QTc, enlarged U wave and apparent T-U complex and these ECG features suggested the repolarization abnormalities of the heart in these subjects.

Ivabradine has a neutral effect on mortality in randomized controlled trials.

BACKGROUND: It has long been a controversial hotspot whether resting heart rate (RHR) is a risk factor or a marker for death. Ivabradine, a specific inhibitor of the If current in the sinoatrial node, is a pure RHR lowering agent. The study was aimed to investigate whether ivabradine would reduce more RHR, cardiovascular disease (CVD) mortality, and all-cause mortality than those placebo or beta-blockers. METHODS: The authors performed a meta-analysis of 8 randomized controlled clinical studies (with 40,357 participants), and 3 studies of those which were ivabradine versus placebo (36,069 participants) and other 5 studies ivabradine versus beta-blockers (4288 participants) were available. The authors compared the association of the RHR reduction with death from CVD causes (2674 in 40,285 participants) and the rate of all-cause death (3143 deaths in 38,037 participants), and assessed improvement in death rates with the use of ivabradine. RESULTS: The change of RHR from baseline to endpoint was 8 to 16 beats/min (bpm) in ivabradine group, 1 to 8 bpm in placebo group, and 4 to 24 bpm in beta-blockers group. In ivabradine versus placebo, the reduced risks of CVD mortality and all-cause morbidity were not significantly (risk ratio [RR] 1.02; 95% confidence interval [CI] 0.91-1.14, P = .737; RR: 1.00, 95% CI: 0.92-1.09, P = .992, respectively). CVD and all-cause morbidity were similar for ivabradine versus beta-blockers (RR: 1.04; 95% CI: 0.80-1.37, P = .752; RR: 1.17, 95% CI: 0.53-2.60, P = .697, respectively). CONCLUSIONS: Ivabradine had a neutral effect on mortality, suggesting that a pure RHR lowering agent did not reduce CVD mortality, all-cause mortality and improve the lifespan.

[The influence of diabetes mellitus on the procedural and in-hospital outcomes after selective percutaneous coronary intervention].

OBJECTIVE: To compare the procedural and in-hospital outcomes in a large series of diabetic and non-diabetic patients undergoing selective percutaneous coronary intervention (PCI) and to evaluate the influence of diabetes mellitus on the procedural and in-hospital outcomes. METHODS: 1294 consecutive patients underwent selective PCI from January to December 2002 in this institution were analyzed retrospectively. Baseline clinical, in-lab and in-hospital outcome information were recorded. Rates of procedural success, device success and clinical success were analyzed and logistic regression was performed to model the association between diabetes status and outcomes. RESULTS: Two hundred and sixty-nine patients (20.8%) complicated with diabetes. Type C lesion, double and triple vessel diseases were more prevalent in diabetics than those in non-diabetics. The pre-PCI diameter stenosis of diabetics was significantly more severe than that of non-diabetics (91.00 +/- 6.62 vs 89.81 +/- 6.64, P < 0.01). The balloon length, maximum balloon diameter and maximum balloon inflation pressure, maximum inflation duration were larger in diabetics than those in non-diabetics [(17.07 +/- 6.31) mm vs (16.07 +/- 7.28) mm, (2.30 +/- 1.11) mm vs (2.12 +/- 0.94) mm, (9.86 +/- 4.40) atm vs (9.05 +/- 4.75) atm, (20.94 +/- 14.69) s vs (18.26 +/- 14.65) s, respectively, P < 0.05]. The stent diameter was smaller in diabetics than that in non-diabetics [(3.15 +/- 0.47) mm vs (3.23 +/- 0.43) mm, P < 0.05]. The procedural success rate showed no significant difference between two groups (89.6% vs 90.3%, P > 0.05). But a higher incidence of acute/subacute stent thrombosis was observed in diabetics compared with that in non-diabetics (1.9% vs 0.5%, P < 0.05). The rate of clinical success was similar between diabetics and non-diabetics (99.3% vs 99.2%, P > 0.05). Diabetes was not an independent predictor of acute outcomes in the regression model. CONCLUSIONS: A higher incidence of acute/subacute stent thrombosis was observed in diabetics. The incidence of procedural and in-hospital major adverse cardiac events and the rate of clinical success were similar between diabetics and non-diabetics. Diabetes was not an independent predictor of in-hospital outcomes after selective PCI.

Oxidative stress in patients with acute coxsackie virus myocarditis.

OBJECTIVE: To study the state of oxidative stress in patients with acute coxsackie virus myocarditis (ACM), and to investigate the pathological chain reactions of a series of free radicals and oxidative and lipoperoxidative damages in their bodies. METHODS: Eighty ACM patients and 80 healthy adult volunteers (HAV) were enrolled in a case-control study, in which concentrations of nitric oxide (NO) in plasma, lipoperoxides (LPO) in plasma and LPO in erythrocytes (RBC), vitamin C (VC), vitamin E (VE) and beta-carotene (beta-CAR) in plasma as well as activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in RBC were determined by using spectrophotometric assays. RESULTS: Compared with the average values (AV) of the above biochemical parameters (BP) in the HAV group, the AV of NO in plasma, and LPO in plasma and RBC in the ACM group were significantly increased (P = 0.0001), while the AV of VC, VE, beta-CAR, SOD, CAT and GSH-Px in the ACM group were significantly decreased (P = 0.0001). The values of the above BP were used to estimate the relative risk ratio (RR) between the ACM group and the HAV group; the RR and its 95% confidence interval were 12.467 (5.745-27.051), 4.333 (2.126-8.834), 6.517 (3.225-13.618), 3.310 (1.598-6.858), 31.000 (12.611-76.201), 4.663 (2.228-9.759), 11.769 (5.440-25.462), 3.043 (1.486-6.229) and 6.594 (3.045-14.281) respectively, and their P levels ranged from 0.002 to 0.0001. The results were as follows: D = 22.143 - 0.017SOD + 0.008NO + 0.244LPO in RBC, Eigenvalue = 13.659, Canonical correlation = 0.965, Wilks' lambda = 0.068, chi 2 = 420.212, P = 0.0001. The correct rate of discrimination to the ACM group and to the HAV group was 87.5% and 95.0%, respectively, and 91.3% of originally grouped cases was correctly classified. CONCLUSION: The findings in this study suggested that the oxidative stress in bodies of ACM patients was severely aggravated, and marked high oxidative constituents and low antioxidants and antioxidases in the human body might increase the relative risk of inducing acute coxsackie virus myocarditis, and measuring the values of NO in plasma, SOD and LPO in RBC might increase the correct rates of discriminatory analysis of the ACM.

[Clinical evaluation of risk factors for coronary heart disease].

OBJECTIVE: To explore the relationship between risk factors for coronary heart disease (CHD) and coronary artery lesions. METHOD: Potential risk factors were studied in 341 patients underwent coronary angiography. RESULTS: (1) Coronary angiography showed coronary artery lesions in 214 patients (lesion group), and no lesion in 127 patients (non-lesion group). There was significant difference in age, past history of diabetes, family history of CHD, smoking history, high-density lipoprotein cholesterol (HDL-C), lower-density lipoprotein cholesterol (LDL-C), ratio of total cholesterol to HDL-C (TC/HDL-C), lipoprotein(a) [Lp(a)], fibrinogen (Fbg) and high-sensitivity C-reactive protein (hs-CRP) between two groups (P < 0.05). (2) There was significant correlation between severity of coronary artery lesions and hs-CRP, Lp(a), TC/HDL-C, Fbg, hyperlipidemia, TC, LDL-C and TG (with coefficients of correlation of 0.338, 0.250, 0.241, 0.207, 0.167, 0.147, 0.140 and 0.139; respectively, P < 0.05). (3) Analysis of receiver operating characteristics (ROC) curve for patients with coronary angiography and risk factors for CHD showed that the areas under ROC curve were 0.810, 0.669, 0.626, 0.625, 0.619 and 0.618 for hs-CRP, TC/HDL-C, Lp(a), Fbg, LDL-C and past history of hyperlipidemia, respectively. CONCLUSIONS: Past history of hyperlipidemia was a predictor for occurrence of CHD. Ratio of TC/HDL-C and blood level of Lp(a) could be used as predictors in screening for high blood lipid, which were much stronger than others. It is suggested that hs-CRP had an excellent predictive value in current coronary inflammatory lesions.