[Multiple effect of simvastatin on vascular endothelium of hypercholesterolemia patients].

OBJECTIVE: To observe the multiple influence of cholesterol-lowering drug (simvastatin) on ankle brachial index (ABI), flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of brachial artery blood vessel endothelium, and plasma level of monocyte chemotactic protein 1 (MCP-1) of hypercholesterolemia patients without coronary heart disease (CHD). METHODS: In the study, 51 patients with hypercholesterolemia application were treated with simvastatin (20 mg/d) therapy for 12 weeks. The metabolic index, ankle brachial index (ABI), FMD of brachial artery blood vessel endothelium detected by color doppler ultrasound instrument, the NMD of artery endothelial and the level of MCP 1 were measured before and after therapy respectively. All the results were analyzed and compared with another 30 cases of hypercholesterolemia patients selected without simvastatin treatment. RESULTS: After simvastatin therapy, the TC (total cholesterol) and LDL-C (low density lipoprotein cholesterin) levels were reduced apparently,the values decreased from the original (6.06 ± 1.03) mmol/L and (3.60 ± 0.82) mmol/L to (4.98 ± 1.34) mmol/L and (3.41 ± 0.10) mmol/L respectively (P<0.01, P< 0.05). Compared with no simvastatin treatment, the bilateral ABI levels were significantly elevated. The right side of ABI (ABIR) elevated from 1.11 ± 0.06 to 1.19 ± 0.07, and the left side of ABI (ABIL) also elevated from 1.12 ± 0.06 to 1.19 ± 0.10 (both sides were P<0.01). The FMD significantly increased from 7.75% ± 11.30% to 14.20% ± 15.39% (P < 0.05). The plasma levels of MCP-1 were apparently reduced from (112.0 ± 7.8) ng/L to (108.9 ± 6.2) ng/L (P < 0.05). All these items showed no obvious change within the control group. CONCLUSION: The API, FMD and plasma levels of MCP-1 of hypercholesterolemia patients without clear coronary heart disease can be improved by simvastatin treatment.

[Correlation of large artery stiffness and coronary flow velocity reserve].

OBJECTIVE: Coronary flow velocity reserve (CFVR) is an important indicator of coronary endothelial functions and microcirculation. Pulse wave velocity (PWV) reflects the degree of aortic sclerosis and it is an independent predictor of cardiovascular events. The present study was designed to evaluate the correlation of large artery stiffness and CFVR. METHODS: A total of 101 consecutive subjects were enrolled to measure the brachial-ankle pulse wave velocity (baPWV). According to the presence or absence of higher baPWV (> 1400 cm/s), they were divided into 2 groups. Transthoracic echocardiography was employed to measure coronary flow velocity in coronary left anterior descending (LAD). Then after an intravenous infusion of adenosine triphosphate, the velocity of blood flow was measured when the vessel was in maximal dilation. The ratio of flow velocity of those in maximal dilation to those at rest was CFVR. RESULTS: The subjects with a higher baPWV (> 1400 cm/s) were markedly elder and had higher risks of hypertension and diabetes. Thus age, hypertension and diabetes contributed to arteriosclerosis. More importantly, the subjects with a higher baPWV (> 1400 cm/s) had a much lower level of CFVR (2.66 ± 0.74 vs 2.95 ± 0.76; P < 0.01) than those with a lower baPWV (< 1400 cm/s). Furthermore correlation analysis showed that CFVR and baPWV levels were significantly negatively correlated (r = -0.35, P < 0.01). CONCLUSIONS: A negative correlation exists between artery stiffness and coronary flow velocity reserve. The increased vascular stiffness may impair coronary endothelial function, cause the dysfunction of coronary microcirculation and raise the risks of cardiovascular events.

[Effects of advanced glycation end products on the secretion of proinflammatory chemokines in vascular smooth muscle cells].

OBJECTIVE: To investigate the effects of advanced glycation end products (AGEs) on the secretion of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in vascular smooth muscle cells (VSMCs) and explore its possible intracellular signaling mechanism. METHODS: Primary rat VSMCs were isolated and identified. VSMCs were treated with glycation serum albumin (GSA), an important component of AGEs, in series of concentrations and time. The role of MAPK and NF-κB inhibitors was confirmed. The levels of MCP-1 and IL-8 were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: VSMCs were treated with GSA at the doses of 10 µg/ml, 100 µg/ml and 500 µg/ml respectively. In comparison with the control group, the levels of MCP-1 (13.01 ng/ml ± 0.12 ng/ml vs 7.02 ng/ml ± 0.26 ng/ml, P < 0.05) and IL-8 (12.6 ng/ml ± 0.86 ng/ml vs 3.07 ng/ml ± 0.35 ng/ml, P < 0.05) increased in the GSA-treated group, especially at the concentration of 100 µg/ml. After adjustment for cells proliferation, the levels of MCP-1 and IL-8 were still higher in the GSA-treated group. After a pretreatment of PDTC (10 µmol/L), SB203580 (5 µmol/L) and MG132 (10 µmol/L), the levels of MCP-1 and IL-8 decreased. However, it had no change when pretreated with PD98059 (20 µmol/L). CONCLUSION: GSA promotes the secretion of MCP-1 and IL-8 in VSMCs. Such an effect is not dependent on cellular proliferation. It may be realized through an activation of NF-κB by p38MAPK-sensitive intracellular signaling pathway.

[A case report of left ventricular apical systolic dysfunction syndrome].

The left ventricular apical systolic dysfunction syndrome was a rare acute cardiac syndrome. Its clinical presentation and electrocardiography were similar to acute myocardial infarction. The syndrome was characterized by transient ventricular wall-motion abnormalities involving the left ventricular apex and mid-ventricle in the absence of obstructive epicardial coronary disease. Cardiac enzyme was normal or minor elevation. At present, the cause of the syndrome is unknown. In this paper, we describe a 56-year-old female patient. She was admitted in hospital for acute appendititis and the transient left ventricular apical ballooning syndrome. She developed acute heart failure and septic shock in the hospital. The drainage of the appendiceal abscess was done and the heart failure and septic shock recovered completely in a few days.

Synergistic proliferation induced by insulin and glycated serum albumin in rat vascular smooth muscle cells.

Hyperglycemia, advanced glycation end products (AGEs), hyperinsulinemia and dyslipidemia may play roles in the development of diabetes-associated atherosclerosis and post-angioplasty restenosis. Clinically, their effects seem to be synergic. However, few studies have focused on the synergistic action of these factors. In the present study, we investigated whether glycated serum albumin (GSA) has a synergistic effect with insulin on the proliferation of vascular smooth muscle cells (VSMCs). VSMCs were isolated from rat thoracic aortas and cultured in fetal bovine serum (FBS)-free medium for 24 h, then exposed to GSA, insulin or GSA + insulin for 48 h with or without pretreatment of mitogen-activated protein kinase (MAPK) inhibitors or the antioxidant N-acetylcysteine (NAC). Cell growth rate was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay or cell counting. The changes of phosphorylated-p38 MAPK and phosphorylated-C-Jun N-terminal kinase 1/2 (JNK1/2) were measured by Western blot analysis. The results showed that only p38 MAPK, but not JNK was activated by GSA and insulin co-incubation. VSMC proliferation was increased by insulin (10-1000 nmol/L) or GSA (10, 100 microg/mL). Co-incubation of insulin (100 nmol/L) and GSA (100 mug/mL) caused a more potent increase in VSMC proliferation than insulin or GSA incubation alone. p38 MAPK inhibitor, SB203580, as well as NAC, could inhibit the VSMC proliferation induced by co-incubation of GSA and insulin. The results show that insulin enhances GSA-induced VSMC proliferation, which may be mediated through a reactive oxygen species (ROS)-p38 MAPK pathway. The synergism of AGEs and insulin may play a detrimental role in the pathogenesis of diabetic atherosclerosis and post-angioplasty restenosis.

[Anti-apoptotic effects of mesenchymal stem cells on cardiac myocytes: in vitro study with rats].

OBJECTIVE: To investigate the anti-apoptotic effects of mesenchymal stem cells (MSCs) on hypoxia-injured cardiac myocytes. METHODS: MSCs were isolated from the bone marrow of 6 - 8 week-old Sprague-Dawley rats. Cardiac myocytes from neonatal rat were cultured under hypoxia, then the hypoxia-injured cardiac myocytes were divided into 3 groups: cultured alone (control group), co-cultured with the MSCs, or co-cultured in MSC-conditioned media in conditions of anoxia (95% N(2) + 5% CO(2), continuous hypoxia group) or normoxia [hypoxia/reoxygen (H/R) group] for 72 hours. The cell apoptosis was measured by Hoechst staining, and Western blotting was used to test the protein expression of Bcl-2 and Bax in the cardiac myocytes. RESULTS: The apoptotic rate of the cardiac myocytes cultured under hypoxia was 51.6% +/- 2.4%, significantly higher than those of the cardiac myocytes co-cultured with MSCs and MSC-conditioned media respectively (15.1% +/- 5.4% and 24.0% +/- 4.2% respectively, both P < 0.001). The apoptotic rate of the H/R group was 20.9% +/- 2.7%, significant higher than that of the MSC group (11.5% +/- 3.7%, P < 0.05), however, not significantly different from that of the MSC-conditioned media group (20.1% +/- 4.2%, P > 0.05). The protein expression of Bcl-2 was not significantly different among different groups. The Bax protein expression of the MSC group and MSC-conditioned media group were 2.28 +/- 0.46 and 3.01 +/- 0.26 respectively, both significantly lower than that of the control group (7.62 +/- 1.28, both P < 0.05). The decreased expression of Bax in the cardiac myocytes was greatly related to the decreasing of apoptosis. CONCLUSION: Co-cultured MSCs show significant anti-apoptotic effects on cardiac myocytes both in continuous hypoxia and in H/R conditions with the possible mechanism of direct cell to cell interaction and paracrine of cytokines which effect the expression of Bax in the myocytes.

[Folic acid attenuates homocysteine induced human monocytes chemokine secretion via reducing NADPH oxidase activity].

OBJECTIVE: To investigate the effect of folic acid on homocysteine (Hcy)-induced chemokine secretion and NADPH oxidase activity in human monocytes. METHODS: Human monocytes from healthy volunteers were incubated with Hcy (100 micromol/L) with or without folic acid (5 micromol/L) for 24 h; MCP-1 and IL-8 were assessed by ELISA. DCFH-DA was added to monitor intracellular ROS production on confocal microscopy. A cytochrome c reduction assay was used to measure NADPH oxidase activity. RESULTS: The Hcy-induced secretion of MCP-1 and IL-8 was significantly reduced by folic acid [(1.88 +/- 0.51) ng/ml vs. (4.36 +/- 0.72) ng/ml vs. (2.40 +/- 0.60) ng/ml and (4.9 +/- 1.9) ng/ml vs. (12.7 +/- 1.5) ng/ml vs. (7.2 +/- 1.9) ng/ml, all P < 0.05]. The Hcy-induced production of ROS was also significantly attenuated by folic acid. Moreover, the Hcy-induced NADPH oxidase activity increase was significantly inhibited by cotreatment with folic acid. CONCLUSION: Folic acid may attenuate oxidative stress induced by Hcy by reducing NADPH oxidase activity in monocytes.

[The changes of electrocardiogram and impact of early invasive strategy in patients with acute coronary syndromes without ST-segment elevation].

OBJECTIVE: To investigate the changes of electrocardiogram (ECG) and impact of early invasive strategy in patients with acute coronary syndrome (ACS) without ST-segment elevation. METHODS: Five hundred and forty-five consecutive ACS patients without ST-segment elevation were randomly assigned to early conservative treatment group and early invasive treatment group. The combined cardiovascular events, including cardiac death, nonfatal myocardial infarction, nonfatal heart failure, and re-hospitalization due to recurrent ischemia angina, within 30 days and 6 months were analyzed and the effects of varied ECG changes and different intervention strategies on outcomes of patients were evaluated. RESULTS: The incidences of each and combined cardiovascular events were higher in the patients with ST-segment depression than in those without ST-segment depression. ST-segment depression was one of independent predictive factors for an increase in cardiovascular events within 6 months (OR 3.864, 95% CI: 1.668 approximately 9.451, P < 0.001). Early invasive strategy was associated with a lower rate of re-hospitalization due to recurrent ischemia angina within 30 days and a decreased incidence of combined cardiovascular events within 30 days and 6 months in comparison with the early conservative treatment group (all P < 0.05). Subgroup analysis implied that incidences of combined cardiovascular events within 30 days and 6 months decreased significantly only in patients with ST-segment depression treated with early invasive strategy, and no such benefit was seen in the patients without ST-segment depression. CONCLUSION: ST-segment depression is an effective indicator for identifying those patients with non-ST segment elevation ACS most likely to benefit from early invasive strategy. Early invasive strategy markedly decreases the cardiovascular events in ACS patients with ST-segment depression than early conservative strategy.

[Prediction of 2-year outcome by combining TIMI myocardial perfusion grading with sum ST segment resolution in patients with acute myocardial infarction].

OBJECTIVE: To evaluate the value of combining TIMI myocardial perfusion (TMP) grading with sum ST segment resolution (sumSTR) in prediction of the 2-year outcome and heart function in patients with acute myocardial infarction (AMI) after emergency percutaneous intervention (PCI). METHODS: Seventy-seven consecutive patients of AMI with elevated ST segment, 62 males and 15 females, aged 63 +/- 12 (30-91), underwent PCI. TMP grading was used in combination of electrocardiography to calculate the sumSTR so as to evaluate the effect of myocardial reperfusion. The patients with TMP grade 2-3 and sumSTR > or = 30% were included in the group of better perfusion, and those with the TMP grade 0-1 and sumSTR < 30% were included in the group of lower perfusion. The cardiac events, including death, reinfarction, revascularization, angina pectoris, and heart failure were recorded. The left ventricular end-diastolic dimension (LVEDD) and left ventricular ejection fraction (LVEF) were measured by echocardiography 72 hours and 2 years after the PCI. RESULTS: There were 37 patients in the lower perfusion group and 39 patients in the better perfusion group. Cos regression showed that TMP grade 0-1 associated with sumSTR < 30% was an independent factor for 2-year cardiac events (RR = 13.186, 95% CI 2.149 - 80.917, P = 0.005). The LVEDD 2 years after PCI was 60 mm +/- 4 mm, significantly higher than that 72 hours after PCI (53 mm +/- 4 mm. P < 0.01) in the lower perfusion group. The LVEDD increased by 7.1 mm +/- 1.9 mm two years after PCI in the lower perfusion group, significantly more than that in the better perfusion group (1.5 mm +/- 1.2 mm, P < 0.01). The myocardial perfusion after PCI was closely correlated with the extent of heart function improvement 2 years after (chi(2) = 50.58, P < 0.01). CONCLUSION: TMP grading combined with sumSTR helps predict the 2-year outcome and heart function in the patients with AMI after emergency PCI.

Effect of homocysteine on plaque formation and oxidative stress in patients with acute coronary syndromes.

BACKGROUND: Cardiovascular diseases, especially coronary artery disease (CAD), are major causes of death in industrialized countries. Elevated concentrations of plasma homocysteine (Hcy) have been associated with an increased risk of CAD. Increased plasma levels of chemokine, characterized by their ability to induce migration and activation of leukocytes, may contribute to the pathogenesis of CAD. This study was designed to investigate the changes of plasma Hcy, monocyte chemoattractant protein-1 (MCP-1) and oxidative stress markers in acute coronary syndrome patients. METHODS: A total of 149 subjects were divided into four groups: 50 patients with unstable angina, 30 patients with acute myocardial infarction, 20 coronary restenosis patients after percutaneous coronary intervention and 49 healthy control subjects. Plasma levels of Hcy, MCP-1, malondialdehyde and superoxide dismutase were measured. RESULTS: Plasma levels of Hcy and MCP-1 showed significant increases in unstable angina, acute myocardial infarction and restenosis patients compared with control subjects (P < 0.05, respectively). Plasma levels of malondialdehyde were significantly increased in unstable angina and acute myocardial infarction patients when compared with control subjects (P < 0.05, respectively). Plasma superoxide dismutase levels were significantly reduced in acute myocardial infarction patients when compared with control group (P < 0.01). CONCLUSION: Hcy might act as an atherogenic factor through promoting chemokine, reactive oxygen species and oxidized low density lipoprotein production and thereby convert a stable plaque into an unstable potentially occlusive lesion.

Calcitonin gene-related peptide gene therapy suppresses reactive oxygen species in the pancreas and prevents mice from autoimmune diabetes.

Reactive oxygen species (ROS) is involved in autoimmune destruction of islet beta cells, which has been proven to be an important underlying pathogenesis for insulin dependent diabetes mellitus (IDDM). Calcitonin gene-related peptide (CGRP) is a widely distributed neuropeptide, which has been found to play an important role in protecting myocytes from ROS. We hypothesized that exogenous CGRP gene administration before the pathogenic stage of insulitis might suppress the production of ROS and provide a hopeful therapeutic intervention for autoimmune diabetes. We performed CGRP gene transfer by injecting naked plasmid directly into skeletal muscles of mice with electroporation enhancement to achieve a continuous expression of CGRP in skeletal muscles, and thereby its secretion into the circulation. The effect of CGRP gene transfer on the pathogenesis of diabetes was studied in autoimmune diabetic mice induced by multiple low dose streptozotocin (MLDS). The CGRP gene therapy decreased morbidity of autoimmune diabetes, and significantly ameliorated hyperglycemia in these mice. CGRP gene transfer inhibited the production of ROS and malondialdehyde (MDA). In addition, it enhanced the activity of catalase (CAT) and superoxide dismutase (SOD) significantly. The data suggest that intramuscular CGRP gene transfer ameliorates autoimmune destruction of islet beta cells, resulting in significant reduction in diabetes incidence of MLDS diabetes mice. CGRP benefits might be mediated at least in part by inhibiting the oxidative stress in islet beta cells of these mice.

[Acute coronary syndrome is a common clinical manifestation of in-stent restenosis].

OBJECTIVE: To study the common clinical manifestations of in-stent restenosis. METHODS: Of 431 patients who underwent percutaneous coronary intervention and repeat catheterization between January 1, 1996 and December 31, 2002, 236 consecutive patients with recurrent ischemia and restenosis were identified: 188 patients with (group I) and 48 without (group II) stenting. Patients who developed early acute stent thrombosis were excluded from the study. In the study we compared the clinical manifestations of in-stent restenosis with those of restenosis without stenting. RESULTS: Recurrent clinical ischemia occurred at a mean of 5.3 months in group I and 6.1 months in group II (P > 0.05). Rest angina (Braunwald class 2 and 3, 43% vs 27%, P < 0.05), the combination of rest angina and acute myocardial infarction (43% vs 27%, P < 0.05), and angiographically visible thrombosis (7% vs 0%, P < 0.05) were more frequent in group I than in group II. CONCLUSION: Acute coronary syndromes are the common clinical manifestations of restenosis in patients undergoing percutaneous coronary intervention and occur more frequently in patients with in-stent stenosis than in those with restenosis without stenting.

[Clinical manifestation and prognosis of myocardial bridge].

OBJECTIVE: To study the clinical manifestation, angiographic features, and prognosis of myocardial bridge. METHODS: A retrospective analysis was made on the data of the clinical manifestation, coronary angiography, and prognosis of 35 patients with myocardial bridge, 29 males and 6 females, with an average age of 52.0 +/- 9.5 years, out of 2 871 patients undergoing coronary angiography 1 January 1996 - 20 February 2001. RESULTS: The detection rate of myocardial bridge, mostly in the middle or distal parts of left anterior descending branch and 24 being isolated myocardial bridge, was 1.22% in coronary angiography. There was a significant difference in the extent of diameter stenosis during systolic stage between the group with atherosclerosis (68% +/- 15%, n = 15) and the group without atherosclerosis (54% +/- 14%, n = 20) in the vessel proximal to myocardial bridge (P < 0.01). The systolic diameter stenosis was more severe in the abnormal ECG group (63% +/- 13%, n = 12) than in the normal ECG group (54% +/- 14%, n = 12), P < 0.05. However, the systolic stenosis extent of myocardial bridge in the patients with typical angina pectoris (58% +/- 15%, n = 11) was not significantly different from that in the patients with atypical angina pectoris (54% +/- 15%, n = 13). The systolic stenosis extent of myocardial bridge were 69% +/- 9% (n = 7) and 58% +/- 16% (n = 26) in the patients with and without left ventricular wall hypertrophy respectively (P = 0.09). No malignant event occurred during the follow-up period of 3 - 50 months. CONCLUSION: (1) The more severe the extent of systolic diameter stenosis, the more severe the myocardial ischemia and the more the possibility of abnormal ECG. (2) Myocardial bridge tends to promote or accelerate the atherosclerosis of the vessels proximal to it. (3) Left ventricular wall hypertrophy may promote the formation of myocardial bridge clinically. (4) The prognosis of myocardial bridge is good.

Association between serum resistin level and cardiovascular events in postmenopausal women with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: As an adipocytokine, resistin has been proposed as a link between inflammation, metabolic disorder and atherosclerosis. The aim of the study is to evaluate whether serum resistin is associated with acute coronary syndrome (ACS) and major adverse cardiovascular events (MACEs) among postmenopausal women with ACS undergoing percutaneous coronary intervention (PCI). METHODS: A total of 106 consecutive postmenopausal women who underwent coronary angiography for evaluation of suspected myocardial ischemia were enrolled. Pre-procedure serum resistin, inflammatory and metabolic biomarkers were measured. All participants were followed for seven years for MACEs, including cardiovascular death, recurrent nonfatal myocardial infarction, and re-PCI. RESULTS: Patients with ACS (n = 69) had significantly higher resistin levels than those without coronary artery disease (CAD) (n = 37) (4.61 (1.79 - 10.80) ng/ml vs. 2.36 (0.85 - 4.15) ng/ml, P = 0.002). Correlation analysis revealed positive correlations between resistin levels and inflammatory and metabolic factors (P < 0.05). A follow-up of a mean of 83.4 months showed that patients with ACS suffered more MACEs than those without (13.0% vs. 2.7%, P = 0.05). Adjusted for cardiovascular risks, inflammatory and metabolic factors, multiple Logistic regression analysis indicated that an elevated resistin level was an independent predictor of ACS onset (OR = 1.139, 95%CI 1.024 - 1.268, P = 0.017) and of MACEs after PCI (OR = 1.099, 95%CI 1.015 - 1.189, P = 0.019). To clarify the association between resistin levels and MACEs, ACS patients were divided into two subgroups on the basis of resistin levels. Compared with the low resistin subgroup (≤ 4.35 ng/ml, n = 32), patients in the high resistin subgroup (> 4.35 ng/ml, n = 37) were more prone to suffer MACEs (21.6% vs. 3.1%, P = 0.015). Kaplan-Meier analysis showed a significantly lower event-free survival rate in ACS patients with high resistin levels than in the low resistin subgroup (78.4% vs. 96.9%, Log rank 5.594, P = 0.018). CONCLUSION: An elevated serum resistin level is associated with ACS and cardiovascular events and acts as a predictor in progression of ACS in postmenopausal women.

Low density lipoprotein cholesterol level inversely correlated with coronary flow velocity reserve in patients with Type 2 diabetes.

OBJECTIVES: To evaluate the association of coronary artery endothelial function and plasma levels of low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in patients with Type 2 Diabetes Mellitus (DM). METHODS: We investigated 90 participants from our institution between October 2007 to March 2010: non-DM (n = 60) and DM (n = 30). As an indicator of coronary endothelial dysfunction, we used non-invasive Doppler echocardiography to quantify coronary flow velocity reserve (CFVR) in the distal part of the left descending artery after rest and after intravenous adenosine administration. RESULTS: Plasma level of LDL-C was significantly higher in patients with DM than in non-DM (3.21 ± 0.64 vs. 2.86 ± 0.72 mmo/L, P < 0.05), but HDL-C level did not differ between the groups (1.01 ± 0.17 vs. 1.05 ± 0.19 mmo/L). Furthermore, the CFVR value was lower in DM patients than non-diabetics (2.45 ± 0.62 vs. 2.98 ± 0.68, P < 0.001). Plasma levels of LDL-C were negatively correlated with CFVR in all subjects (r = -0.35, P < 0.001; 95% confidence interval (CI): -0.52 - -0.15) and in the non-DM (r = -0.29, P < 0.05; 95% CI: -0.51- -0.05), with an even stronger negative correlation in the DM group (r = -0.42, P < 0.05; 95% CI: -0.68 - -0.06). Age (ß = -0.019, s = 0.007, sß = -0.435, 95% CI: -0.033 - -0.005, P = 0.008), LDL-C (ß = -0.217, s = 0.105, sß = -0.282, 95% CI: -0.428 - -0.005, P = 0.045) remained independently correlated with CFVR in the DM group. However, we found no correlation between HDL-C level and CFVR in any group. CONCLUSIONS: Diabetes may contribute to coronary artery disease (CAD) by inducing dysfunction of the coronary artery endothelium. Increased LDL-C level may adversely impair coronary endothelial function in DM. HDL-C may lose its endothelial-protective effects, in part as a result of pathological conditions, especially under abnormal glucose metabolism.

Thorombolytic therapy with rescue percutaneous coronary intervention versus primary percutaneous coronary intervention in patients with acute myocardial infarction: a multicenter randomized clinical trial.

BACKGROUND: Although thrombolytic therapy with rescue percutaneous coronary intervention (PCI) is a common treatment strategy for ST-segment elevation acute myocardial infarction (STEMI), scant data are available on its efficacy relative to primary PCI, and comparison was therefore the aim of this study. METHODS: This multicenter, open-label, randomized, parallel trial was conducted in 12 hospitals on patients (age < or = 70 years) with STEMI who presented within 12 hours of symptom onset (mean interval > 3 hours). Patients were randomized to three groups: primary PCI group (n = 101); recombinant staphylokinase (r-Sak) group (n = 104); and recombinant tissue-type plasminogen activator (rt-PA) group (n = 106). For all patients allocated to the thrombolytic therapy arm, coronary angiography was performed at 90 minutes after drug therapy to confirm infarct-related artery (IRA) patency; rescue PCI was performed in cases with TIMI flow grade < or = 2. Bare-metal stent implantation was planned for all patients. RESULTS: After randomization it required an average of 113.4 minutes to start thrombolytic therapy (door-to-needle time) and 141.2 minutes to perform first balloon inflation in the IRA (door to balloon time). Rates of IRA patency (TIMI flow grade 2 or 3) and TIMI flow grade 3 were significantly lower in the thrombolysis group at 90 minutes after drug therapy than in the primary PCI group at the end of the procedure (70.5% vs. 98.0%, P < 0.0001, and 53.0% vs. 85.9%, P < 0.0001, respectively). Rescue PCI with stenting was performed in 117 patients (55.7%) in the thrombolytic therapy arm. Rates of patency and TIMI flow grade 3 were still significantly lower in the rescue PCI than in the primary PCI group (88.9% vs. 97.9%, P = 0.0222, and 68.4% vs. 85.0%, P = 0.0190, respectively). At 30 days post-therapy, mortality rate was significantly higher in the thrombolysis combined with rescue PCI group than in primary PCI group (7.1% vs. 0, P = 0.0034). Rates of death/MI and bleeding complications were significantly higher in the thrombolysis with rescue PCI group than in the primary PCI group (10.0% vs. 1.0%, P = 0.0380, and 28.10% vs. 8.91%, P = 0.0001, respectively). CONCLUSIONS: Thrombolytic therapy with rescue PCI was associated with significantly lower rates of coronary patency and TIMI flow grade 3, but with significantly higher rates of mortality, death/MI and hemorrhagic complications at 30 days, as compared with primary PCI in this group of Chinese STEMI patients with late presentation and delayed treatments.

Functional alpha1-adrenergic receptor subtypes in human right gastroepiploic artery.

AIM: To study the functional alpha1-adrenergic receptor (alpha1-AR) subtypes in human right gastroepiploic artery (RGA). METHODS: The effects of alpha2-AR, alpha1-AR, and alpha1-AR subtype selective antagonists on norepinephrine (NE)-induced vasoconstriction in isolated human RGA were observed by contractile function experiment. RESULTS: Cumulative concentration-response curves for NE were competitively antagonized in RGA by alpha2-AR selective antagonist yohimbine (pA2 6.82+/-0.28, slope 1.12+/-0.40),alpha1-AR selective antagonist prazosin (pA2 9.77+/-0.22, slope 0.90+/-0.22),alpha1A-AR selective antagonists RS17053 (pA2 8.42+/-0.20, slope 0.93+/-0.20) and 5-MU (pA2 8.42+/-0.22, slope 0.88+/-0.18),alpha1D-AR selective antagonist BMY7378 (pA2 6.84+/-0.32, slope 1.05+/-0.17), and alpha1A-,alpha1B-AR selective antagonist WB4101 (pA2 8.88+/-0.20, slope 1.15+/-0.16). The correlation coefficients between these pA2 values of alpha1-AR selective antagonists with pKi values of which obtained from alpha1A-, alpha1B- and alpha1D-AR cloned cells are 0.95, 0.82, and 0.42. After the vessels were pretreated by chlorethylclonidine (CEC), an alpha1B- and alpha1D-AR irreversible alkylating agent, the pD2 values were changed from 5.9+/-0.5 to 5.6+/-0.6 and the maximal contraction was changed from (8.9+/-3.2) g to (8.0+/-3.2) g, respectively. The difference was not significant. CONCLUSION: In human RGA, the contraction response is mainly mediated by alpha1-AR, of which alpha1A-AR plays an important role, whereas alpha1B- and alpha1D-AR are not involved in the contraction response.