In-stent Anchoring Facilitating Side-branch Balloon Delivery for Final Kissing: A Prospective, Single-center Registry Study.

BACKGROUND: Recrossing the compromised side branch (SB) with a balloon is sometimes technically challenging. The aim of this study was to evaluate whether in-stent anchoring (ISA) is safe and effective to facilitate SB balloon delivery for final kissing. METHODS: One hundred and fifty-nine consecutive patients were included (166 bifurcation lesions) in this prospective, single-center registry. ISA was used as a bailout method after unsuccessful SB crossing using conventional techniques, including low-profile balloons. Technique success was defined as SB balloon delivery and final kissing. RESULTS: Kissing-balloon delivery was successfully performed with conventional strategies in 149 of 166 lesions (89.8%). In the remaining 17 lesions (10.2%), recrossing of the main vessel stent strut was not successful; therefore, ISA was attempted. The balloon successfully crossed the stent struts, and final kissing was achieved in 15 of 17 lesions (88.2%). Total final kissing was achieved in 164 of 166 lesions (98.8%), with success rates of 100% in the single-stent group and 97.6% in the two-stent group. Two cases without balloon delivery had complex bifurcation lesions with severe calcification. There was no vessel dissection in the anchoring zone. CONCLUSIONS: ISA is safe and effective for recrossing stent struts when conventional low-profile balloons have failed. However, large-scale trials are warranted for further evaluation.

Protective effect of a polysaccharide from Salvia miltiorrhiza on isoproterenol (ISO)-induced myocardial injury in rats.

In this study, we investigated the cardioprotective effect of one purified polysaccharide (SMP1) from Salvia miltiorrhiza on isoproterenol (ISO)-induced myocardial infarction (MI) in rats. ISO-treated rats showed severe myocardial damage and high lipid peroxidation level, as well as decreased endogenous myocardial antioxidant function. Pretreatment with SMP1 (100 and 400mg/kg) for 30 days significantly increased the body weight, decreased the heart weight, attenuated the serum levels of creatine kinase (CK), creatine phospokinase-MB (CK-MB), dehydrogenase (LDH), alkaline phosphate (ALP), aspartate transaminase (AST), alanine transaminase (ALT), total cholesterol, triglyceride, and LDL-cholesterol (LDL-C), along with the increased concentration of HDL-cholesterol (HDL-C). In addition, SMP1 also enhanced myocardial superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities and elevated myocardial reduced glutathione (GSH) level, along with a decrease in thiobarbituric acid reactive substances (TBARS) concentration. Collectively, our results indicated that long-term oral administration of SMP1 offered significant protection against the damage induced by ISO in rat heart through enhancement of endogenous antioxidants and antihyperlipidemic activity.

Cardiovascular effects in vitro of a polysaccharide from Salvia miltiorrhiza.

A polysaccharide (SMP1) was isolated from the roots of Salvia miltiorrhiza. This study is designed to investigate whether SMP1 prevents H9c2 cells from hydrogen peroxide (H2O2)-induced apoptosis. The present study showed that exposure of H9c2 cells to 100mM H2O2 for 24h caused a significant increase in cell death and apoptosis, but pretreatment with SMP1 eliminated H2O2-induced apoptotic cell death. Furthermore, pretreatment with SMP1 significantly prevented the mitochondria disruption, cytochrome c release, the rise of the ratio between proapoptotic Bax and antiapoptotic Bcl-2 protein expression, and caspase-3 activation in H9c2 cells upon H2O2 stimulation. Moreover, the decline of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities together with the elevation of malondialdehyde (MDA) in PC12 cells exposed to H2O2 were remarkably reversed to normal levels by pretreatment with SMP1. These results suggest that SMP1 protects H9c2 cells from H2O2-induced apoptosis through inhibition of mitochondrial dysfunction, inactivation of caspase-3 cascade and enhancement of antioxidant capacity.

Evaluation on the efficacy and safety of domestic bivalirudin during percutaneous coronary intervention.

BACKGROUND: Bivalirudin was widely used as an anticoagulant during coronary interventional procedure in western countries. However, it was not available in China before this clinical trial was designed. This randomized, single-blind and multicenter clinical trial aimed to evaluate the efficacy and the safety of domestic bivalirudin during percutaneous coronary intervention (PCI). METHODS: A randomized, single-blind, multicenter trial was designed. Elective PCI candidates in five centers were randomized into a bivalirudin group and a heparin group, which were treated with domestic bivalirudin and non-fractional heparin during the PCI procedure. The efficacy was evaluated by comparing the activated coagulation time (ACT), the procedural success rate (residual stenosis < 20% in target lesions without any coronary artery related adverse events within 24 hours after PCI), and the survival rate without major adverse cardiac events at 30 days after PCI between the two groups. Safety was evaluated by the major/minor bleeding rate. RESULTS: A total of 218 elective PCI patients were randomized into a bivalirudin group (n = 110) and heparin group (n = 108). Except for two patients needing additional dosing in the heparin group, the ACT values of all other patients in both groups were longer than 225 seconds at 5 minutes after the first intravenous bolus. Procedural success rates were respectively 100.0% and 98.2% in the bivalirudin group and heparin group (P > 0.05). Survival rates without major adverse cardiac events at 30 days after PCI were 100.0% in the bivalirudin group and 98.2% in the heparin group (P > 0.05). Mild bleeding rates were 0.9% and 6.9% (P < 0.05) at 24 hours, and 1.9% and 8.8% (P < 0.05) at 30 days after PCI in the bivalirudin group and heparin group respectively. There was one severe gastrointestinal bleeding case in the heparin group. CONCLUSIONS: Domestic bivalirudin is an effective and safe anticoagulant during elective PCI procedures. The efficacy is not inferior to heparin, but the safety is superior to heparin.

Clinical outcome and left ventricular remodeling in AMI patients with insufficient myocardial reperfusion after recanalization.

AIM: Myocardial contrast echocardiography (MCE) is effective in predicting myocardial viability and functional recovery on a segmental level in patients with acute myocardial infarction (AMI). In this study, we investigated whether insufficient myocardial reperfusion plays an important role in left ventricular (LV) remodeling and functional recovery in patients with thrombolysis in myocardial infarction (TIMI) flow grade 3 and corrected TIMI frame count (CTFC) < 40 after recanalization of the infarct-related artery. METHOD: Patients underwent intracoronary injection of microbubbles for echocardiographic assessment of myocardial microvascular perfusion, wall motion score, LV volume and ejection function (EF) at baseline, 30 minutes, one month and six months after recanalization. The patients with MCESI < 1 were considered to have insufficient myocardial reperfusion (group A, n=11), while the patients with MCESI≥1 were considered to have sufficient myocardial reperfusion (group B, n=47) after AMI recanalization. RESULTS: The wall motion score index (WMSI) and the left ventricular ejection fraction (LVEF) showed significant improvement at 1 month and 6 months in group B, but only at six months in group A. Left ventricular end-systolic and end-diastolic volumes (LVESV and LVEDV) were also significantly decreased at one and six months in group B. WMSI, LVESV, LVEDV and LVEF were significantly improved in group B in comparison with group A at one month and six months (P < 0.01). By six months, significant correlations were seen in all patients between MCESI and changes in LVESV, LVEDV and LVEF at 6 months. Similar correlations were observed between the myocardial regional blood flow (Q) and changes in LVESV , LVEDV and LVEF. CONCLUSION: Insufficient myocardial reperfusion was a strong independent predictor of LV remodeling and functional recovery in AMI patients with TIMI flow grade 3 and CTFC < 40 after recanalization. MCE has important additional value for prognosis and risk assessment in patients with acute myocardial infarction following recanalization.

Isolation and characterization of human coronary artery-derived endothelial cells in vivo from patients undergoing percutaneous coronary interventions.

BACKGROUND/AIMS: Human coronary artery-derived endothelial cells (ECs) seem to be the most appropriate cells for the pathogenesis study of coronary artery disease. But limited availability of endothelial tissue is a major constraint. In this study, we developed a method to isolate human coronary artery ECs in vivo from patients. METHODS: Coronary guidewires were used to obtain EC samples from coronary arteries in 76 patients. Cells were eluted from wire tips and purified by immunomagnetic beads. Von Willebrand factor and CD31 were used as immunocytochemical markers to identify cells as endothelium. Cell viability was evaluated in terms of cell membrane integrity, energy-dependent uptake of DiI-labeled acetylated low-density lipoprotein, and apoptosis. Nitric oxide synthase (eNOS) expression and nitric oxide (NO) production of cells were detected to evaluate cell function. RESULTS: About 96 coronary artery ECs were obtained per guidewire. Cells manifested endothelial morphology and immunoreactivity for von Willebrand factor and CD31 with good viability. But eNOS expression and NO production of cells were decreased. CONCLUSIONS: Viable coronary endothelium could be obtained during routine percutaneous coronary interventions combined with immunomagnetic beads. These cells may be used for advanced cellular functional analyses such as immunocytochemistry and molecular biology. Such information could aid in understanding mechanisms of coronary artery diseases.

[Identification of human coronary artery endothelial cells obtained by coronary endovascular biopsy].

OBJECTIVE: To develop a method to obtain and identify human coronary artery endothelial cells obtained during percutaneous coronary interventions (PCI). METHODS: Coronary guide wires were used to obtain endothelial cells from coronary arteries in 28 patients undergoing PCI. The cells were eluted from the wire tips and then purified by magnetic beads coated with anti-CD146 antibody. von Willebrand factor (vWF) was used as an immunocytochemical marker for endothelial cells. The cellular viability was evaluated by observing cell membrane integrity and energy-dependent uptake of DiI-labeled acetylated low-density lipoprotein. RESULTS: An average of 96 coronary artery endothelial cells with good viability per patient were obtained by one guide wire. vWF identification showed their endothelial morphology and immunoreactivity. CONCLUSION: The viable coronary endothelial cells could be obtained during routine percutaneous coronary interventions combined with magnetic beads isolation technique. These cells may be used for further cellular functional analyses (such as immunocytochemistry and molecular biology) and expand our understanding on mechanisms of coronary artery diseases.

[Association among circulating endothelial progenitor cells, insulin resistance and severity of coronary lesions in patients with coronary artery disease].

OBJECTIVE: To investigate the correlation between the number and activity of circulating endothelial progenitor cells (EPCs), insulin resistance and severity of coronary lesions in patients with coronary artery disease (CAD). METHODS: Patients with coronary angiography evidenced CAD were divided in insulin resistance group (IR, n = 25) and insulin sensitive group (IS, n = 44) according to insulin level, 25 health volunteers served as control. Circulating EPCs were marked as KDR/CD133+ cells via fluorescence-activated cell sorter analysis. EPCs were also isolated from peripheral blood and cultured in vitro for 7 days, identified by DiI-acLDL uptake and lectin staining methods. EPCs migration activities were determined by modified Boyden chamber assay, EPCs proliferation activities were determined by MTT assay. RESULT: Circulating EPCs number was significantly lower in IR group compared with IS group [(0.34 +/- 0.08) per thousand vs. (0.47 +/- 0.09) per thousand, P < 0.01] and control group (P < 0.05). Both insulin resistance index (r = -0.291, P = 0.01)and Gensini score (r = -0.3984, P = 0.006)were negatively correlated with number of circulating EPCs. Proliferation and migration capacities of EPCs were also significantly lower in IR group compared to those in IS group (all P < 0.05) and control group (all P < 0.05). CONCLUSIONS: Insulin resistance/hyperinsulinemia could aggravate severity of coronary artery lesions via reducing the number and activities of circulating EPCs in patients with CAD.

Value of myocardial regional perfusion on long-term function in collateral-dependent myocardium.

BACKGROUND: Collateral circulation is considered key for left ventricular (LV) function recovery in patients with chronic total occlusion (CTO). However, there are conflicting reports about the influence of collaterals on LV recovery after revascularization. METHODS: Echocardiographic assessment of regional myocardial perfusion, wall motion score (WMS), and left ventricular ejection fraction (LVEF) were performed in patients with angiographically visible collateral circulation of grades 2 and 3. RESULTS: The WMS and LVEF of group B (with presence of myocardial regional perfusion) were significantly improved at one month and six months compared to those of group A (with absence of myocardial regional perfusion). The correlation between myocardial regional blood flow and changes in WMS and LVEF was significant at 6 months in patients with angiographically visible collateral circulation of grade 2 and 3. Similar correlations were observed on myocardial contrast echocardiography (MCE) score index. CONCLUSION: Myocardial function recovery in patients with CTO is determined by myocardial regional perfusion. MCE has important value for prognosis and risk stratification in patients with CTO undergoing cardiac catheterization.

[Significance of the ratio of circulating endothelial cell expressing endothelial lipase and supersensitivity C-reactive protein in prognosis of patients with coronary artery disease].

OBJECTIVE: To evaluate the significance of the ratio of circulating endothelial cell expressing endothelial lipase (EL(+)/CECs) and supersensitivity C-reactive protein (hsCRP) in prognosis of patients with coronary artery disease (CAD). METHODS: one hundred and seven patients with acute coronary syndrome (ACS), 69 patients with stable angina pain (SAP), and 82 patients in whom CAD was excluded to serve as control were included for study. Blood samples were collected from ulnar vein, and hsCRP was detected, circulating endothelial cells (CECs) were isolated, and the ratio of CEC (EL(+)/CECs) which expressed endothelial lipase (EL) was determined by immunohistochemistry. Over a follow-up period of 6 months, the incidence of cardiac event of all patients was recorded. RESULTS: In patients with CAD, the EL(+)/CECs and hsCRP were significantly different among groups (P<0.05 or P<0.01). Among them, hsCRP and EL(+)/CECs were higher in ACS group than SAP group patients, whose hsCRP and EL(+)/CECs higher than the control group. The incidence rate of cardiovascular event was significantly higher (all P<0.01) in those whose hsCRP or EL(+)/CECs was higher than those whose with lower average values of these two parameters. Regression analysis indicated that the EL(+)/CECs and hsCRP could be used as the prognostic factor of CAD. The prognostic value of combined determination of EL(+)/CECs and hsCRP was higher. CONCLUSION: The expression of EL in endothelial cells may play a role in the progression of CAD. The EL(+)/CECs may be a good prognostic factor. EL(+)/CECs together with hsCRP may increase the prognostic value.

[The relationship between circulating endothelial progenitor cells and the risk factors of CHD as well as the severity of coronary lesions, and its clinical significance].

OBJECTIVE: To investigate the correlation between circulating endothelial progenitor cells (EPCs) and the risk factors of coronary heart disease (CHD) as well as the severity of coronary lesions, and its clinical significance. METHODS: 42 patients with CHD and 36 patients excluding CHD (control) were studied. Total mononuclear cells were isolated from peripheral blood by Ficoll density gradient centrifugation, and were cultured in M199 medium supplemented with 20% fetal bovine serum, 50 ng/ml vascular endothelial growth factor (VEGF). After 14 days cultured, the numbers of colony-forming units of EPCs were counted by phase-contrast microscope. The relationship between the number of colony-forming units of EPCs and the risk factors of CHD (such as age, gender, hypertension, hypercholesterolemia, diabetes, smoking, positive family history of CHD) as well as the severity of coronary lesions were assessed. RESULTS: The number of risk factors of CHD was significantly correlated with a reduction of EPCs levels (r = -0.436, P = 0.014). Smoking was associated with significantly lower EPCs levels, whereas a minor but nonsignificant reduction of EPCs levels was detected in the presence of gender, hypertension, and a positive family history of CHD. It was observed that low density lipoprotein (LDL) and uric acid were negatively correlated with the number of colony-forming units of circulating EPCs (P < 0.05). A correlation existed between age, high density lipoprotein, apoprotein A and levels of circulating EPCs, however, this relation was not statistically significant. The number of colony-forming units of circulating EPCs in CHD groups was significantly lower than those in control group (12.8 +/- 6.34 versus 37.0 +/- 5.5, P < 0.001); and the circulating EPCs level of coronary artery lesion group (including single, double, triple vessels disease) was significantly lower than that of control group (P < 0. 01). CONCLUSIONS: The level of circulating EPCs was inversely associated with the risk factor scores of CHD and the severity of coronary artery lesion. These finding imply that endothelial injury in the absence of sufficient circulating EPCs may affect the degree of the heart disorder and the clinical situation.

[Effects of paclitaxel combined with bone marrow stromal stem cells implantation on vascular endothelial repair and smooth muscle cells growth in vitro].

OBJECTIVE: To investigate the effects of paclitaxel combined with bone marrow stromal stem cells (MSCs) implantation on inhibiting the smooth muscle cells (SMCs) growth and promoting endothelial repair by developing an endothelial repair model in vitro. METHODS: In a cell coculture system, rabbit endothelial cells (ECs) and human MSCs were seeded in the lower chamber and rabbit SMCs were seeded in the upper chamber. 3H-TdR incorporation and PCNA protein expression were used to evaluate SMCs proliferation at the 10th day after paclitaxel application (1, 10, 100 nmol/L; 20 min). Fluorescence immunocytochemistry was employed to observe the Flk-1 and vWF protein expression on MSCs. RESULTS: The SMCs 3H-TdR incorporation of the MSCs implant group was significantly lower than that of the proliferative ECs group (1 nmol/L: 12 265 +/- 991 vs. 14 505 +/- 1013 cpm/well; 10 nmol/L: 8401 +/- 783 vs. 10 511 +/- 934 cpm/well; 100 nmol/L: 5880 +/- 569 vs. 7457 +/- 768 cpm/well, n = 6, P < 0.05), but higher than that of the confluent ECs group (1 nmol/L: 12 265 +/- 991 vs. 8671 +/- 642 cpm/well; 10 nmol/L: 8401 +/- 783 vs. 6175 +/- 743 cpm/well; 100 nmol/L: 5880 +/- 569 vs. 4423 +/- 406 cpm/well, n = 6, P < 0.05). The expression of SMCs PCNA protein in MSCs implant group was lower than that of the proliferative ECs group (1 nmol/L: 0.92 +/- 0.06 vs. 1.15 +/- 0.07; 10 nmol/L: 0.97 +/- 0.07 vs. 1.07 +/- 0.08; 100 nmol/L: 0.91 +/- 0.05 vs. 1.18 +/- 0.11, n = 6, P < 0.05), but higher than that of the confluent ECs group (1 nmol/L: 0.92 +/- 0.06 vs. 0.74 +/- 0.07; 10 nmol/L: 0.97 +/- 0.07 vs. 0.78 +/- 0.06; 100 nmol/L: 0.91 +/- 0.05 vs. 0.71 +/- 0.05, n = 6, P < 0.05). The MSCs did not express vWF or Flk-1 protein before coculture. Although none cell expressed vWF, some of the MSCs began to express Flk-1 protein after cocultured with mature ECs for 10 days. CONCLUSION: MSCs implantation can partly inhibit the delayed SMCs proliferation. The MSCs cocultured with paclitaxel-treated mature ECs have the ability to differentiate into ECs.

[The significance and implications of coronary endothelial injury and dysfunction in patients with angina].

OBJECTIVE: To investigate the role of coronary endothelial injury and dysfunction in the development and progress of coronary heart disease. METHODS: 20 patients with unstable angina (UA), 17 patients with stable angina (SA) and 18 patients without coronary heart disease (control) were studied. Nitric oxide (NO), endothelin (ET) and circulating endothelial cells (CEC) were measured with both coronary sinus and peripheral blood during percutaneous coronary intervention (PCI). RESULTS: The level of NO in either coronary sinus or peripheral blood in patients with UA was lower, while the level of ET and CEC was markedly higher than that in the SA and control group (P < 0.01, or P < 0.05); The level of NO in SA was lower, while the level of ET and CEC was higher than those in the control group (P < 0.01, or P < 0.05). In UA patients, the level of NO in coronary sinus blood was lower (P < 0.05), while the level of ET and CEC was higher (P < 0.01, or P < 0.05) than that in peripheral blood. Similar differences appeared in patients with SA, but no obvious difference between coronary sinus and peripheral blood was observed in the control group (P > 0.05). CONCLUSIONS: It is suggested that coronary endothelial injury and dysfunction occur universally in angina patients, being consistent with the severity of coronary heart disease. Aggravation of coronary endothelial injury and dysfunction may contribute to the progress of the disease and may be the pathophysiological basis of acute coronary incidents.