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.

[Autologous mesenchymal stem cell implantation promotes myocardial expressions of growth factors and improves cardiac function in failing rat hearts].

OBJECTIVE: To explore the underlying mechanism of mesenchymal stem cells (MSCs) transfer induced cardiac function improvement in failing hearts. METHODS: Congestive heart failure (CHF) was induced in rats by cauterization of the heart wall. MSCs were cultured from autologous bone marrow and injected into the border zone and the remote myocardium 5 days after cauterization. RESULTS: Ten weeks later, cardiomyocyte nucleus mitotic index, capillary density and expression of insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) were significantly increased in the border zone and significantly reduced in the remote myocardium in CHF rats (all P<0.05 vs. sham). Besides cardiac function improvement and left ventricular remodeling attenuation evidenced by hemodynamic and echocardiographic examinations, expressions of IGF-1, HGF and VEGF in the remote myocardium and in the border zone were also significantly upregulated (P<0.05 or P<0.01 vs. CHF), and cardiomyocyte nucleus mitotic index as well as capillary density were significantly increased in CHF rats with MSCs (P<0.05 or P<0.01 vs. CHF). Moreover, collagen area was significantly reduced and myocardial area was significantly increased in the border zone in these rats too. CONCLUSION: Autologous MSC implantation upregulated expressions of growth factors enhanced cardioangiogenesis which might be the underlying mechanisms for improved cardiac function and attenuated left ventricular remodeling induced by MSCs transplantation in failing rat myocardium.

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.

[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.

[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.

[Beneficial effects of probucol on endothelial function in patients with acute coronary syndrome].

OBJECTIVE: The study investigate the antioxidant probucol on endothelial function in patients with acute coronary syndrome (ACS). METHODS: A total of 49 ACS patients randomly received standard therapy plus probucol (P, n = 24) or standard therapy (C, n = 25). Plasma oxidized low-density lipoprotein (ox-LDL), nitric oxide (NO) and circulating endothelial cells (CEC) were measured. The brachial arterial hyperemia-induced flow mediated dilation (FMD) and sublingual nitroglycerin (NTG) mediated vasodilatations were measured by high resolution ultrasound. These variables were analyzed before and after 3 months therapy. RESULTS: Plasma NO and FMD was significantly increased after 3 months therapy than before therapy [(80.46 +/- 10.24) micromol/Lvs (48.46 +/- 12.24) micromol/L, P < 0.01; (13.46 +/- 1.20)% vs (7.45 +/- 1.02)%, P < 0.05, respectively], while the number of CEC and ox-LDL were significantly decreased (P < 0.01) in P group. These values were similar before and after 3 months in C group. The linear correlation analysis showed that plasma ox-LDL negatively correlated with NO (r = -0.574, P < 0.01) and FMD (r = -0.517, P < 0.01) and positively correlated with CEC (r = 0.385, P < 0.01) in patients received 3 months probucol therapy. CONCLUSIONS: Chronic antioxidant probucol therapy could improve endothelial function in patients with ACS.

[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.

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.

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.

[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.

Growth factors induce the improved cardiac remodeling in autologous mesenchymal stem cell-implanted failing rat hearts.

Therapeutically delivered mesenchymal stem cells (MSCs) improve ventricular remodeling. However, the mechanism underlying MSC cardiac remodeling has not been clearly determined. Congestive heart failure (CHF) was induced in rats by cauterization of the left ventricular free wall. MSCs were cultured from autologous bone marrow and injected into the border zone and the remote myocardium 5 d after injury. Ten weeks later, when compared with sham operation, CHF significantly increased nucleus mitotic index, capillary density, and expression of insulin-like growth factor 1, hepatocyte growth factor and vascular endothelial growth factor in the border zone (P<0.01) and decreased each of them in the remote myocardium (P<0.05 or P<0.01). MSC implantation in CHF dramatically elevated expression of these growth factors in the remote myocardium and further elevated their expression in the border zone when compared with CHF without MSC addition (P<0.05 or P<0.01). This was paralleled by a higher nucleus mitotic index and a significantly increased capillary density both in the remote myocardium and in the border zone, and by a lower percentage of area of collagen and a higher percentage of area of myocardium in the border zone (P<0.05 or P<0.01), and cardiac remodeling markedly improved. Autologous MSC implantation promoted expression of growth factors in rat failing myocardium, which might enhance cardiomyogenesis and angiogenesis, and improved cardiac remodeling.

[Effect of carvedilol and perindopril on Ca(2+) pump activity and Ca(2+)-release channel density in myocardial sarcoplasmic reticulum in rats with chronic heart failure following myocardial infarction].

OBJECTIVE: To study the effects of carvedilol combined with perindopril on Ca(2+) pump activity and the density of Ca(2+)-release channel ryanodine receptor (RyR2) in the myocardial sarcoplasmic reticulum (SR) in rats with chronic heart failure caused by myocardial infarction. METHODS: Rat models of chronic heart failure established by left coronary artery ligation were divided into different groups and treated with carvedilol (6 mg.kg(-1).d(-1)), perindopril (4 mg.kg(-1).d(-1)), terazosin (2 mg.kg(-1).d(-1)), or the combination of carvedilol (6 mg.kg(-1).d(-1)) and perindopril (4 mg.kg(-1).d(-1)) for 9 weeks. Another 12 rats with sham operation served as the sham-operated group. The hemodynamic parameters, activity of SR Ca(2+) pump, and RyR2 density were determined. RESULTS: Compared with shame-operated group, the rats with chronic heart failure showed significantly increased left ventricular end-diastolic pressure (LVEDP) (P<0.01) and decreased +dP/dtmax, -dp/dtmax, activity of SR Ca(2+) pump and density of RyR2 (P<0.01). Both monotherapies with carvedilol and perindopril attenuated the increment of LVEDP, and significantly increased +dp/dtmax, -dp/dtmax, activity of SR Ca(2+) pump and density of RyR2 (P<0.01). Combined treatment even further enhanced the therapeutic effects, whereas terazosin produced no obvious effect. The activity of SR Ca(2+) pump was strongly correlated to +dp/dtmax and -dp/dtmax (r=0.596 and 0.684, respectively, P<0.01). CONCLUSION: Prolonged treatment with beta-blocker carvedilol in combination with ACE inhibitor perindopril may improve the hemodynamic parameters, enhance Ca(2+) pump activity and increase the density of RyR2 of myocardial SR more effectively than either monotherapy in preventing and treating chronic heart failure following myocardial infarction.