Cyclophosphamide protects against myocardial ischemia/reperfusion injury in rats: one of the therapeutic targets is high sensitivity C-reactive protein.

OBJECTIVE: Cyclophosphamide has a role of decreasing high-sensitivity C-reactive protein in the treatment of autoimmune disorders. The effect of cyclophosphasmide on high-sensitivity C-reactive protein was investigated in myocardial ischemia/reperfusion rat. METHODS: Open-chest rats were submitted to 30 minutes of ischemia and followed for 3, 12, or 24 hours of reperfusion. All 72 rats survived and were divided into sham, ischemia/reperfusion (I/R) and cyclophosphamide groups, and each group included 3 time-point subgroups (3, 12, and 24 hours; n = 8 for each subgroup). Cyclophosphamide (0.75 g/m(2)) or saline was intraperitoneally administrated in the cyclophosphamide or I/R group. A polyethylene tube was inserted into the left ventricular cavity to detect left ventricular systolic pressure, left ventricular end-diastolic pressure, and maximum rate of rise or fall of left ventricular pressure. In the end, blood was collected for detection of high-sensitivity C-reactive protein, and hearts were harvested for histopathologic assessment and infarct size determination. RESULTS: Compared with the I/R group, rats treated with cyclophosphamide showed a significant recovery in myocardial function with improved left ventricular systolic pressure (88.27 +/- 3.78 vs 68.62 +/- 3.78 mm Hg at 3 hours, 92.04 +/- 3.77 vs 63.74 +/- 4.87 mm Hg at 12 hours, and 90.41 +/- 3.98 vs 64.21 +/- 4.88 mm Hg at 24 hours; P < .05, respectively). Left ventricular end-diastolic pressure and maximum rate of rise or fall of left ventricular pressure also had similar trends. Infarct size was reduced (26.1% +/- 0.4% vs 40.4% +/- 0.4% at 3 hours, 21.6% +/- 0.4% vs 49.9% +/- 0.4% at 12 hours, and 21.6% +/- 0.4% vs 40.0% +/- 0.4% at 24 hours; P < .01, respectively). Histopathologic damage score was attenuated (1.83 +/- 0.14 vs 2.17 +/- 0.14 at 3 hours, 2.33 +/- 0.14 vs 3.17 +/- 0.14 at 12 hours, and 2.83 +/- 0.14 vs 3.83 +/- 0.14 at 24 hours; P < .01, respectively). Plasma high-sensitivity C-reactive protein concentration was significantly reduced (29.28 +/- 0.51 vs 32.26 +/- 0.51 ng/mL at 3 hours, 29.06 +/- 0.50 vs 31.8 +/- 0.51 ng/mL at 12 hours, and 28.61 +/- 0.51 vs 31.86 +/- 0.51 ng/mL at 24 h; P < .01, respectively). CONCLUSION: Cyclophosphamide protects myocardial ischemia/reperfusion injury in the rat with a decrease in plasma concentration of high-sensitivity C-reactive protein.

Safety and efficacy of autologous endothelial progenitor cells transplantation in children with idiopathic pulmonary arterial hypertension: open-label pilot study.

Experimental data suggest that transplantation of EPCs attenuates monocrotaline-induced pulmonary hypertension in rats and dogs. In addition, our previous studies suggested that autologous EPC transplantation was feasible, safe, and might have beneficial effects on exercise capacity and pulmonary hemodynamics in adults with IPAH. Thus, we hypothesized that transplantation of EPCs would improve exercise capacity and pulmonary hemodynamics in children with IPAH. Thirteen children with IPAH received intravenous infusion of autologous EPCs. The right-sided heart catheterization and 6-MWD test were performed at baseline and at the time of 12 wk after cell infusion. At the time of 12 wk, mPAP decreased by 6.4 mmHg from 70.3 +/- 19.0 to 63.9 +/- 19.3 mmHg (p = 0.015). PVR decreased by approximately 19% from 1118 +/- 537 to 906 +/- 377 dyn s/cm(5) (p = 0.047). CO increased from 3.39 +/- 0.79 to 3.85 +/- 0.42 L/min (p = 0.048). The 6-MWD increased by 39 m from 359 +/- 82 to 399 +/- 74 m (p = 0.012). NYHA functional class also improved. There were no severe adverse events with cell infusion. The small pilot study suggested that intravenous infusion of autologous EPCs was feasible, safe, and associated with significant improvements in exercise capacity, NYHA functional class, and pulmonary hemodynamics in children with IPAH. Confirmation of these results in a randomized controlled trial are essential.

Transplantation of autologous endothelial progenitor cells may be beneficial in patients with idiopathic pulmonary arterial hypertension: a pilot randomized controlled trial.

OBJECTIVES: The goal of this study was to investigate the feasibility, safety, and initial clinical outcome of intravenous infusion of autologous endothelial progenitor cells (EPCs) in patients with idiopathic pulmonary arterial hypertension (IPAH). BACKGROUND: Experimental data suggest that transplantation of EPCs attenuates monocrotaline-induced pulmonary hypertension in rats and dogs. In addition, clinical studies suggest that autologous progenitor cell transplantation is feasible and safe in patients with ischemic diseases. METHODS: We conducted a prospective, randomized trial comparing the effects of EPC transplantation plus conventional therapy with those of conventional therapy alone in patients with IPAH. The primary end point was change in the 6-min walk distance using a standardized protocol. The secondary end points were changes in hemodynamic variables as assessed by right heart catheterization. RESULTS: After 12 weeks of follow-up, the mean distance walked in 6 min increased by 48.2 m in the cell infusion group (from 263 +/- 42 m to 312 +/- 34 m), and an increase of 5.7 m occurred in the conventional therapy group (from 264 +/- 42 m to 270 +/- 44 m). The mean difference between the 2 groups was 42.5 m (95% confidence interval 28.7 to 56.3 m, p < 0.001). The patients in the cell infusion group also had significant improvement in mean pulmonary artery pressure, pulmonary vascular resistance, and cardiac output. There were no severe adverse events with cell infusion. CONCLUSIONS: This preliminary study showed that intravenous infusion of autologous EPCs seemed to be feasible and safe, and might have beneficial effects on exercise capacity and pulmonary hemodynamics in patients with IPAH. (Safety and Efficacy Study of Transplantation of EPCs to Treat Idiopathic Pulmonary Arterial Hypertension; http://www.clinicaltrials.gov/ct/show/NCT00257413?order=1; NCT00257413).

[Alprazolam use improves psychological status and reduces hospitalization costs in patients with paroxysmal supraventricular tachycardia underwent radiofrequency catheter ablation].

OBJECTIVE: To evaluate the effect of alprazolam use on psychological status and hospitalization cost in patient with paroxysmal supraventricular tachycardia underwent electrophysiology studies or radiofrequency catheter ablation. METHODS: In this prospective, randomized, double-blind, placebo-controlled study, 142 inpatients [77 males, mean age (43.1 +/- 14.5) years] were randomly assigned to receive alprazolam (0.4 mg qd at 10PM for 3 days, n = 72) or placebo (n = 70) 3 days before scheduled electrophysiology studies or radiofrequency catheter ablation. All patients were examined by the Chinese version of Symptom Checklist-90 (SCL-90) at 24 hours before the procedure. RESULTS: Compared with the placebo group, the scores of somatization (1.38 +/- 0.40 vs. 1.65 +/- 0.56, P < 0.01), anxiety (1.50 +/- 0.39 vs. 1.69 +/- 0.50, P < 0.05), phobic anxiety (1.24 +/- 0.36 vs. 1.47 +/- 0.57, P < 0.01), psychotism constructs (1.24 +/- 0.34 vs. 1.35 +/- 0.30, P < 0.05) and global severity index (1.36 +/- 0.35 vs. 1.49 +/- 0.37, P < 0.05) were significantly decreased in alprazolam group. The hospitalization costs were also significantly lower in alprazolam group (32 498 +/- 1170) yuan compared to placebo group (32 947 +/- 1096) yuan, P < 0.05. CONCLUSION: The alprazolam use before electrophysiology studies and radiofrequency catheter ablation can improve the patients' psychological status and reduce the hospitalization costs.

[Psychologic status comparison in patients treated with transradial or transfermoral approach coronary catheterizations].

OBJECTIVE: We previously showed that factorial score of somatization, which was obtained by the examination of symptom checklist-90 (SCL-90), was higher in patients received transfemoral coronary catheterization than norm. The aim of the present study was to compare the patient's psychologic status between transradial approach and transfemoral approach percutaneous coronary catheterizations. METHODS: A total of 198 inpatients (105 transfemoral, 93 transradial) underwent scheduled first time coronary catheterizations were enrolled. All patients were studied by symptom SCL-90 on present psychologic status 24 hours before and 24-48 hours after coronary catheterizations. RESULTS: Age, sex, weight, smokers, employment, educational background, marriage status, family relations, family history of cardiovascular disease, income and medical insurance status were similar between the two groups. There was also no difference in diabetes, hypertension history as well as coronary heart disease confirmed by coronary catheterization between the 2 groups. Compared with the status before the procedure, factorial scores of somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, global severity index and total positive symptoms were significantly reduced after percutaneous coronary catheterizations (1.50 +/- 0.51 vs. 1.64 +/- 0.53, 1.50 +/- 0.48 vs. 1.67 +/- 0.55, 1.28 +/- 0.41 vs. 1.38 +/- 0.49, 1.42 +/- 0.43 vs. 1.55 +/- 0.53, 1.38 +/- 0.41 vs. 1.58 +/- 0.54, 1.32 +/- 0.35 vs. 1.44 +/- 0.41, 1.38 +/- 0.34 vs. 1.49 +/- 0.42, and 23.08 +/- 17.30 vs. 27.72 +/- 18.79, respectively, P all < 0.05). Scores on somatization, depression and positive symptom severity index were significantly lower in patients received transradial coronary catheterizations than those received transfemoral coronary catheterization approach (1.52 +/- 0.51 vs. 1.62 +/- 0.53, 1.43 +/- 0.54 vs. 1.54 +/- 0.43 and 2.36 +/- 0.66 vs. 2.50 +/- 0.43, respectively, P all < 0.05). CONCLUSION: Patients' psychologic status improved significantly after percutaneous coronary catheterizations. Improvement on psychologic status is significantly better in patients underwent transradial coronary catheterizations than that underwent transfemoral coronary catheterizations.

Captopril administered at night restores the diurnal blood pressure rhythm in adequately controlled, nondipping hypertensives.

The aim of our study was to evaluate whether captopril administered at night, can shift the circadian blood pressure (BP) from a nondipper to a dipper pattern in adequately controlled hypertensive patients, who continued their antihypertensive therapy. In a prospective, randomized, double blind, placebo-controlled designed study, we enrolled 121 treated, adequately controlled nondipping hypertensive patients. All patients were randomly assigned to 12.5 mg captopril or placebo treatment administered at night. In case of nondippers, the dosage of captopril or placebo was doubled after two weeks of treatment, while for dippers antihypertensive regimens were not changed. After another two weeks, all patients underwent ambulatory BP monitoring. Our results show that at the end of the active treatment period, the prevalence of a dipping diurnal BP pattern in the captopril group (70%) was significantly higher than that in the placebo group (9.8%, P < 0.001). Nighttime BP, night/day BP ratio, nighttime BP load and 24-h systolic BP were significantly lower after 4 weeks nighttime captopril treatment compared to baseline. In conclusion, the present study demonstrates for the first time that captopril administered at night can restore the diurnal BP rhythm and decrease the elevated night/day BP ratio in appropriately controlled, nondipper hypertensive patients. These results were mainly due to the decrease of nighttime BP.

A novel splice mutation of HERG in a Chinese family with long QT syndrome.

Congenital long QT syndrome (LQTS) is a genetically heterogeneous disease in which six ion-channel genes have been identified. The phenotype-genotype relationships of the HERG (human ether-a-go-go-related gene) mutations are not fully understood. The objective of this study is to identify the underlying genetic basis of a Chinese family with LQTS and to characterize the clinical manifestations properties of the mutation. Single strand conformation polymorphism (SSCP) analyses were conducted on DNA fragments amplified by polymerase chain reaction from five LQT-related genes. Aberrant conformers were analyzed by DNA sequencing. A novel splice mutation in C-terminus of HERG was identified in this Chinese LQTS family, leading to the deletion of 11-bp at the acceptor splice site of Exon9 [Exon9 IVS del (-12-->-2)]. The mutation might affect, through deficient splicing, the putative cyclic nucleotide binding domain (CNBD) of the HERG K(+) channel. This mutation resulted in a mildly affected phenotype. Only the proband had a history of syncopes, while the other three individuals with long QT interval had no symptoms. Two other mutation carriers displayed normal phenotype. No sudden death occurred in the family. The 4 affected individuals and the two silent mutation carriers were all heterozygous for the mutation. It is the first splice mutation of HERG reported in Chinese LQTS families. Clinical data suggest that the CNBD mutation may be less malignant than mutations occurring in the pore region and be partially dominant over wild-type function.

[Comparison of the antithrombotlic effect and safety between intravenous nadroparin and unfractionated heparin in patients undergoing percutaneous coronary intervention].

OBJECTIVE: The study was designed to compare the antithrombotic property and safety between nadroparin and unfractionated heparin during percutaneous coronary intervention (PCI). METHODS: A prospective, single blind, randomized study was performed. A total of 98 patients (aged 65.1 +/- 8.6 years, female, 28.6%, diabetes, 7.1%) undergoing selective PCI were randomized to be administered intravenously either nadroparin (0.075 ml/10 kg) or unfractionated heparin (100U/kg) for procedural anticoagulation, in whom stable angina was 42.9%, unstable angina, 27.6%, myocardial infarction, 29.6%, two or three-vessel disease, 23.5%, stent, 100%. Blood samples for anti-Xa level were assayed in the first 22 patients of the nadroparin group before and after administration at the following intervals: 8 min, 1 h, 2 h and 4 h. Bleeding complications were classified according to Thrombolysis In Myocardial Infarction (TIMI) criteria. The bleeding index (change in hemoglobin) was calculated. All patients were monitored for adverse clinical events (i.e. death, myocardial infarction, need for revascularization) during the period of 30 days after PCI. RESULTS: (1) There were no significant differences in baseline characteristics between the two randomized groups. (2) Plasma anti-Xa activities were 0.10 +/- 0.00 IU/ml at the time just before the administration of nadroparin, 1.89 +/- 0.24 IU/ml, 0.96 +/- 0.24 IU/ml, 0.47 +/- 0.13 IU/ml, and 0.30 +/- 0.12 IU/ml at the time of 8 min, 1 h, 2 h and 4 h after the use of nadroparin (and the rate of > 0.5 IU/ml were 100%, 100%, 45% and 9% patients), respectively. (3) There were no significant differences in the mean bleeding index, post-PCI hemoglobin and hematocrit between nadroparin and unfractionated heparin group [(1.16 +/- 5.80) g/L vs (0.90 +/- 6.50) g/L, P = 0.858; (129.5 +/- 13.6) g/L vs (125.5 +/- 14.9) g/L, P = 0.175; (39.0 +/- 3.9)% vs (37.9 +/- 4.6)%, P = 0.205]. (4) None of the patients in two randomized groups were observed hemorrhagic events, which including TIMI major or minor bleeding complications, gross or microscopic hematuria, melena, positive stool occult blood. There were no blood transfusions and no hematoma at the vascular access site in either of the group. (5) No death, no recurrent angina pectoris, and no urgent revascularization occurred within 30 days in both groups. One patient in nadroparin group was observed "no reflow" phenomenon that was accompanied with an elevated ST segment and a risen serum level of cTnI. This patient was diagnosed as non-Q-wave myocardial infarction. Though no myocardial infarction was found in unfractionated heparin group, there was no significant difference in the rate of myocardial infarction between the two groups of the study (P = 0.970). CONCLUSIONS: The administration of nadroparin before PCI seems effective and safe. Compared with unfractionated heparin, nadroparin was associated with neither an excess of bleeding nor an increase of clinical complications in this study.

[Profile on circadian blood pressure and the influencing factors in essential hypertensive patients after treatment].

OBJECTIVE: To explore the circadian blood pressure (BP) profile and its influencing factors in essential hypertensive patients after treatment. METHODS: Cross-sectional surveillance was carried out in essential hypertensive subjects after treatment whose clinic blood pressure had been under control as 140/90 mm Hg (1 mm Hg = 0.133 kPa) for at least one month. All patients underwent a twenty-four-hour ambulatory blood pressure monitoring device (spacelabs 90207). The nocturnal fall of blood pressure (BP) was calculated from (daytime mean BP-night-time mean BP)/daytime BP, while 'daytime' values were recorded between 6 h and 22 h and 'night-time' values between 22 h and 6 h. Non-dippers were defined as those whose nocturnal decrease in mean systolic BP and/or mean diastolic BP was < 10% of the daytime BP. Binary logistic regression analysis was used to evaluate the correlation between circadian blood pressure profile and factors as gender, age, height, body mass index (BMI), family history of premature cardiovascular disease, women under age 65 or men under age 55, smoking habits, grade of hypertension, and strategy of antihypertensive drugs. RESULTS: 208 treated essential hypertensive patients were enrolled in the study. 79 individuals were dippers and 129 were non-dippers. Data from logistic regression analysis showed that four factors as age, premature family history of cardiovascular disease, overweight or obesity, and strategy of antihypertensive drugs were significantly influencing the circadian blood pressure profile in treated hypertensive patients. The incidence of non-dippers in patients of 70 years of age or older and those between 60 and 69 were 3.3 and 2.3 times of those with less than 60 (P = 0.009 and 0.031, respectively). The prevalence of non-dippers in patients with a premature family history of cardiovascular disease was 3.7 times greater than those in subjects without a premature history of cardiovascular disease (P = 0.029). Similarly, the incidence of non-dippers in patients of overweight (24 /= 28) were 3.0 and 4.8 times of those in subjects of normal weight (P = 0.003 and 0.009, respectively). Compared with patients treated with long-acting calcium channel blockers (CCBs), patients treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) alone had less prevalence of nondippers (OR = 0.139, P = 0.010). Patients treated with joint antihypertensive scheme including ACE inhibitors or ARBs(but not including diuretics) had the tendency of lower incidence of abnormal circadian blood pressure rhythm (OR = 0.453, P = 0.118). Patients treated with joint antihypertensive scheme including diuretics (not including ACE inhibitors or ARBs) and with joint antihypertensive strategy including diuretics and ACE inhibitors or ARBs had lower incidence of nondippers (OR = 0.378 and 0.273, respectively; P = 0.030 and 0.011, respectively). CONCLUSIONS: Approximately 2/3 treated essential hypertensive patients had a non-dipper blood pressure profile. Age, premature family history of cardiovascular disease, overweight/obesity, and antihypertensive drugs strategy were correlated with circadian blood pressure profile. Compared with long-acting CCBs, diuretics, ACE inhibitors or ARBs might be helpful in keeping the circadian blood pressure rhythm at normal range.

[Identification of a novel mutation at the point of low density lipoprotein receptor gene from a subject with familial hypercholesterolemia].

Family hypercholesterolemia (FH) is a genetic disorder caused by mutation in the low density lipoprotein receptor (LDLR) gene. It is characterized by a high concentration of low density lipoprotein (LDL), which frequently gives rise to tendon xanthenes and premature coronary artery disease. We studied a FH family ,which was diagnosed by clinical features and blood lipid tests. The Total cholesterol level of the family was 19.05 mmol/L and the LDL level was 17.06 mmol/L in the proband homozygous FH subjects, while the total cholesterol was 7.96 mmol/L and LDL was 5.55 mmol/L in the heterozygous FH subjects. DNA segments amplified with PCR were sequenced in heterozygous and homozygous FH patients. Two novel identical mutation alleles of GAG683GCG, which caused an amino acid change from Glu to Ala, were detected in Exon4 of LDL receptor gene in homozygous proband. DNA sequencing revealed that the proband's parents were heterozygotes with the same mutational alleles as the proband. These results are in coincidence with the clinical diagnoses. Moreover Epstein-Barr virus transformed lymphocytes (EBV-Ls) were derived by routine virus infection transforming protocol. The cells bounded with the fluorescently conjugated LDL were measured by fluorescence flow cytometry. The ratios of functional LDLR in EBV-Ls originated from homozygous FH, heterozygous FH and normal control were 7.02%, 62.64% and 84.69%, respectively. As a result, the homozygous FH patient's LDLR had 8.29% and the heterozygous FH patient's LDLR had 73.96% of the activity of the control. It is apparent that LDL receptor activity of homozygous FH subject is significantly lower than normal control. The data from fluorescence flow cytometry analysis of EBV-Ls strongly support the clinical diagnoses and the results of DNA sequencing. In accordance with the updated version of UMD-LDLR, the mutant GAG683GCG in Exon4 of LDLR gene which we have identified is a novel mutation of the LDLR gene in human with hypercholesterolemia.

Statins contribute to enhancement of the number and the function of endothelial progenitor cells from peripheral blood.

The aim of the present study was to investigate whether fluvastatin augments the number of endothelial progenitor cells (EPCs), and promotes EPCs proliferation, migration and adhesion. Total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll density gradient centrifugation. The cells were then plated on fibronectin-coated culture dishes. After being cultured for 7 d, the attached cells were stimulated with fluvastatin (final concentrations: 0.01, 0.1, 1, 10 micromol/L), simvastatin (1 micromol/L) or a vehicle for the respective time points (6, 12, 24 and 48 h). EPCs were characterized as adherent cells double positive for DiLDL-uptake and lectin binding by direct fluorescent staining under a laser scanning confocal microscope. EPCs were further documented by demonstrating the expression of KDR, VEGFR-2 and AC133 with flow cytometry. EPCs proliferation, migration and in vitro vasculogenesis activity were assayed by MTT assay, modified Boyden chamber assay and in vitro vasculogenesis kit, respectively. EPCs adhesion assay was performed by replating it on fibronectin-coated dishes, and the adherent cells were then counted. In addition, we also studied EPCs culture assay of peripheral blood from fluvastatin-treated animals in vivo. Incubation of isolated human MNCs with fluvastatin dose- and time-dependently increased the number of EPCs, while reached the maximum 24 h after the administration at 1 micromol/L, (2.5-fold increase, P<0.05). Moreover, treatment of rats with fluvastatins elevated the number of EPCs (3-fold increase, P<0.05), thus extending the in vitro data. In addition, fluvastatin also promoted EPC proliferation, migration, adhesion and in vitro vasculogenesis in a concentration-dependent manner. The effects of fluvastatin on EPCs were compared with those of simvastatin at the same concentration (1 micromol/L), with a result of no statistical difference. The results of the present study define a novel mechanism of the action of statins: the augmentation of EPCs with enhanced functional activity.

[Effects of hypercholesterolemia on the number and activity of endothelial progenitor cells in peripheral blood].

OBJECTIVE: To investigate whether hypercholesterolemia has influences on the number and activity of endothelial progenitor cells (EPCs). METHODS: Mononuclear cells were isolated from patients with hypercholesterolemia (n = 20) and age-matched control subjects (n = 20). EPCs were characterized as adherent cells double positive for DiLDL-uptake and lectin binding by direct fluorescent staining under a laser scanning confocal microscope. EPCs proliferation and migration were assayed by MTT assay and modified Boyden chamber assay, respectively. EPCs adhesion assay was performed by replating cells on fibronectin-coated dishes, then counting the adherent cells. RESULTS: The number of EPCs was significantly reduced in patients with hypercholesterolemia as compared with that in control subjects [(41.8 +/- 8.7 vs 64.5 +/- 16.6) EPCs/x 200 fields; P < 0.05] and it was inversely correlated with total cholesterol levels (r = -0.659, P < 0.001) and LDL cholesterol levels (r = -0.611, P < 0.001). In addition, EPCs proliferative, migratory and adhesive capacity were also impaired. CONCLUSION: It is suggested that a novel pathophysiological mechanism of hypercholesterolemia may be defined i.e. reduction of EPCs with decreased functional activity.

[Expression of connexin in atrium of patients with atrial fibrillation and its signal transduction pathway].

OBJECTIVE: To explore the expression of connexin (Cx) and its signal transduction pathway in the atrium of patients with atrial fibrillation (AF). METHODS: Atrial tissue samples of 63 patients undergoing cardiac surgery, including patients with chronic AF or paroxysmal AF (PAF), and those with sinus rhythm, were collected during operation. The mRNA expressions of calcineurin B and mitogen-activated protein kinase-1 (MKP-1) were detected by semi-quantitative RT-PCR. The protein expressions of extracellular-signal regulated kinase 1 (ERK1), phospho-ERK1 (P-ERK1), Cx40 and Cx43 were analyzed by Western blotting. HE staining and immunohistochemistry were used to examine the distribution of Cx40 and Cx 43. RESULTS: Increased amounts of Cx40 protein (left atrium: 2.2 +/- 0.8, 2.2 +/- 0.6; right appendages: 2.1 +/- 0.5, 2.0 +/- 0.8) were found in the left atrium and right appendages of patients with Chronic persistent AF (CAF) or paroxysmal AF (PAF) (P < 0.05). The expression of Cx43 was only increased in the left atrium of patients with CAF and PAF (3.1 +/- 0.6, 2.8 +/- 0.7 vs 1.0 +/- 0.2, both P < 0.05). The amounts of Calcineurin B mRNA, MKP-1 mRNA and P-ERK1 of patients with CAF or PAF were significantly increased compared with patients in sinus rhythm (P < 0.05). Immunohistochemistry revealed that Cx40 and Cx43 of CAF patients and PAF patients acculmated in the intracellular site, and at the lateral member of atrial cells, both connexins redistributed. CONCLUSION: The increased expression and disorderly distribution of Cx 40 and Cx 43 protein in the atrium of AF patients may be related with the abnormal activation and disequilibria of regulation of ERK1, MKP-1 and calcineurin.

Number and activity of endothelial progenitor cells from peripheral blood in patients with hypercholesterolaemia.

Hypercholesterolaemia contributes to atherosclerosis and coronary artery diseases by inducing endothelial cell injury and dysfunction. Recent studies have provided increasing evidence that EPCs (endothelial progenitor cells) participate in ongoing endothelial repair and postnatal neovascularization. However, the changes in EPCs in patients with hypercholesterolaemia have not been elucidated to date. Therefore we investigated the number and functional activity of EPCs in patients with hypercholesterolemia. Total MNCs (mononuclear cells) were isolated from 20 patients with hypercholesterolaemia and 20 matched control subjects. EPCs were characterized as adherent cells double-positive for DiI-LDL (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanide percholate-labelled low-density lipoprotein) uptake and lectin binding by direct fluorescent staining under a laser scanning confocal microscope, and were characterized further by demonstrating the expression of KDR (kinase insert domain-containing receptor), CD34 and AC133 by flow cytometry. Proliferation, migration and in vitro vasculogenesis activity of EPCs were assayed using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay, modified Boyden chamber assay and an in vitro vasculogenesis kit respectively. EPC adhesion assay was performed by replating cells on fibronectin-coated dishes and then counting the adherent cells. As a result, the number of EPCs was significantly reduced in patients with hypercholes-terolaemia compared with that in control subjects (41.8 +/- 8.7 compared with 64.5 +/- 16.6 EPCs/x 200 field respectively; P < 0.05). The number of EPCs was inversely correlated with total cholesterol (r = -0.659, P < 0.001) and LDL-cholesterol (r = -0.611, P < 0.001) levels. In addition, the functional activities of isolated EPCs, such as proliferative, migratory, adhesive and in vitro vasculogenesis capacity, were also impaired. In conclusion, the results of the present study may state a novel pathophysiological mechanism of hypercholesterolaemia: the reduction of EPCs with decreased functional activity.

[Endothelium-independent vasorelaxant effect of puerarin on rat thoracic aorta].

OBJECTIVE: To investigate the vasorelaxant effect of puerarin in rat aortic rings and the mechanism. METHOD: The isolated thoracic aortic rings of male Sprague-Dawley rats were mounted on the organ bath and the contractile responses of the vessel were recorded. RESULT: Puerarin completely relaxed the contractions induced by phenylephrine in a concentration-dependent manner in endothelium-intact and endothelium-denuded rat aorta, but it had no effect on those preconstricted by a high concentration of potassium chloride (KCl, 60 mmol x L(-1)). The relaxant effect of puerarin was significantly inhibited by pretreatment of endothelium-denuded aorta with potassium channel antagonists tetraethylammonium, 4-aminopyridine but not glibenclamide. CONCLUSION: Puerarin induces an endothelium-independent relaxation in rat aortic rings. The mechanisms may involve the reduction in Ca2+ influx through the calcium channels operated by alpha-adrenergic receptor and the activation of the potassium channels (Kv and BKca, but not KATP).

[Psychological status and its influencing factors on patients undergoing electrophysiology studies and radiofrequency catheter ablation].

OBJECTIVE: To study the psychological status and its influencing factors in patients before and after electrophysiology studies and radiofrequency catheter ablation (RFCA). METHODS: 125 inpatients (71 men, 54 women, mean age 42.91 years +/- 16.1 years) who underwent a scheduled electrophysiology studies and RFCA for the first time and fulfilled entry criteria, were enrolled. They were randomly assigned to receiving either a consent which did not detail specific risk (group B) regarding the procedure or one that detailed the risks (group A). All patients were examined by the Chinese version of Symptom Check List-90 (SCL-90) within 24 hours before the procedure (after the consent) and on the third day after. RESULTS: (1) Before the electrophysiology studies and RFCA, scores of anxiety and phobic anxiety constructs were higher than the norm. After the procedure, no specific construct score became higher. (2) After the procedure, patients showed a significantly decrease in the scores of obsessive-compulsive, depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychotism constructs, global severity index, total positive symptoms and positive symptom severity index. (3) Women scored higher on somatization, depression, anxiety, phobic anxiety constructs, global severity index and positive symptom total before the procedure. (4) Detail informed consent was not associated with increased mental symptoms when compared with consent that did not detail specific risks. CONCLUSIONS: In this study, patients showed slightly anxiety and phobic anxiety before electrophysiology studies and RFCA with women having more mental symptoms before the procedure that called for special attention. Detail information including the course and specific risk regarding the procedure was not associated with increased psychological symptoms. It was suggested that the patients should receive detail information before electrophysiology studies and RFCA.

[Psychologic status and their influencing factors in patients suspected of coronary disease before and after coronary catheterization].

OBJECTIVE: To study the psychologic status and their influencing factors in patients suspected of having coronary disease before and after coronary catheterization. METHODS: A hundred fifty-eight inpatients (125 men, 33 women, mean age 66.1 +/- 9.6 years) who underwent a scheduled coronary catheterization for the first time and fulfilled entry criteria were enrolled. All the patients were examined by Symptom Check List-90 (SCL-90), a standard self-report symptom inventory on present psychologic status, within 24 hours before the coronary catheterization (after the information consent) and the third day after the procedure. RESULTS: (1) Before coronary catheterization, factorial scores of somatization, anxiety and phobic anxiety were higher than norm (P < 0.05 or P < 0.01). After the procedure, only somatization score was higher (P < 0.01). (2) Men had higher scores on obsessive-compulsive and psychotism than women (P < 0.05 and P < 0.01, respectively), however, women had higher scores on phobic anxiety (P < 0.05). (3) Compared with patients having coronary disease, those with angiographically normal coronary arteries seemed to have higher scores of somatization, obsessive-compulsive, interpersonal sensitivity, phobic anxiety, paranoid ideation, psychotism, global severity index and positive symptoms (P < 0.05 or P < 0.01). (4) After the procedure, significantly decreases in obsessive-compulsive, depression, hostility, global severity index and positive symptom severity index (P < 0.05 or P < 0.01) were seen. (5) Patients merely underwent coronary angiography had higher score in phobic anxiety construct than those having had coronary angiography and percutaneous transluminal coronary angioplasty (1.34 +/- 0.38 vs 1.15 +/- 0.23, P < 0.05). (6) When compared with the degree of explanation under informed consent, specific risk was not informed mentioned, a higher score in positive symptom severity index was seen (2.56 +/- 0.48 vs 2.46 +/- 0.37, P = 0.02). (7) Higher score was seen on positive symptom severity index when patients aged 70 years or more (2.62 +/- 0.45) than those under 60 years old (2.47 +/- 0.43, P < 0.05) or between 60 and 69 years old (2.45 +/- 0.40, P < 0.01). CONCLUSIONS: Patients' psychologic symptoms before and after the coronary catheterization seemed to be related to many factors. The most important appeared one was coronary catheterization itself. Women, patients with angiographically normal arteries, those of 70 years old or more were more likely to have elevated psychologic distress. Detail information including specific risk regarding the procedure was not associated with the increase of psychological symptoms. The findings emphasized the importance of psychologic assessment and counseling for patient who had undergone a scheduled coronary catheterization.

[Relationship of collagen content, intimal thickening and angiotensin II level of iliac arteries after balloon injury in rabbits]

OBJECTIVE: To investigate the relationship of collagen content intimal thickening and angiotensin II level of iliac arteries after balloon injury in rabbits. METHODS Fifty male New Zealand white rabbits were randomly devided into 6 groups: losartan groups, benazapril groups and control groups for 4 weeks or 8 weeks. Every rabbit underwent endothelial debridement of the right iliac artery. lorsartan (15 mg/kg/d) and benazapril (5 mg/kg/d) were orally administrated respectively in losartan groups and benazepril groups from 5 days before until 4 weeks or 8 weeks after balloon injury. RESULTS: Collagen content and intimal area of rabbit iliac arteries were increased after balloon injury. After intervention for 4 weeks with losartan and benazapril, collagen content was decreased in losartan and benazapril groups than in control group 23.58+/-6.16 % and 22.67+/-10.20 % compared with 35.20+/-7.25 % respectively, P<0.05. After intervention for 8 weeks, collagen content was significantly decreased (20.69+/-11.16)% and 25.41+/-11.00 % compared with 42.69+/-13.99 % respectively, P<0.05; Intimal area and intimal to medial area ratio were also decreased in losartan and benazapril groups than in control group; Lumen area was increased in losartan and benazapril groups than in control group(0.79+/-0.25)mm2 and (0.76+/-0.28)mm2 compared with (0.62+/-0.27)mm2 P<0.05; Tissue angiotensin II level was increased in losartan group (516.31+/-70.79)pg/mg.pro compared with (410.72+/-100.11)pg/mg.pro, P<0.05, and decreased in benazapril group than in control group (340.62+/-67.69)pg/mg.pro compared with (410.72+/-100.11)pg/mg.pro, P<0.05. There were close correlation between tissue angiotensin II level and intimal area, or between tissue angiotensin II level and intimal to medial area ratio, or and collagen content in benazapril group, respectively, P<0.05. Conclusion (1) Collagen protein is a dynamic participant in vascular injury. (2) Tissue renin angiotensin system may play an important role in collagen accumulation, intimal thickening and vascular injury after angioplasty. (3) Losartan and benazapril reduce vascular collagen content and inhibit intimal thickening after balloon injury.