PMN-CD11b Levels and Its Correlation with Left Atrial Diameter in Patients with Atrial Fibrillation / 中山大学学报(医学科学版)

@#【Objective】To observe the levels of CD11b expressions in the surface of neutrophils in serum，and its correlation with left atrial diameter ，and to study the inflammatory mechanisms in atrial fibrillation（AF） patients. 【Methods】Clinical characteristics and blood samples of AF group and sinal rhythm group were collected. CD11b levels in the surface of neutrophils were examined by flow cytometry. Left atrial diameter was examined by echocardiography. 【Results】The AF group included 85 patients ：36 with paroxysmal AF；26 with persistent AF；23 with permanent AF. The sinal rhythm group includes 57 patients. PMN- CD11b levels were significantly higher in Af group than in sinal rhythm group（P＜0.01）. The left atrial diameter was larger in AF group than in sinal rhythm group（P＜0.01）. Multivariate analysis revealed that PMN-CD11b，left atrial diameter and Valvular heart disease were independent predictors of atrial fibrillation.【Conclusions】PMN- CD11b levels were elevated in paroxysmal AF when AF was present and in persistent， permanent AF patients，implying atrial fibrillation was closely related to inflammation；PMN-CD11b were correlated with left atrial diameter，inflammation might participate in the atrial structural remodeling in AF patients ；PMN-CD11b levels were elevated in AF patients with high risk thrombosis，inflammation might have some value to embolic risk stratification according to CHA2DS2-VASc score.

Association of higher resistin levels with inflammatory activation and endothelial dysfunction in patients with essential hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Some studies have shown that serum resistin levels increase in hypertensive patients. Whether the increase of resistin is related to inflammatory or vascular endothelial function is still unknown. We investigated the relationship of increased resistin levels to inflammatory factors and circulating biomarkers of vascular endothelial function in hypertensive patients.</p><p><b>METHODS</b>One hundred and forty-four nondiabetic patients with new onset, hypertension were recruited. Blood pressure, blood glucose, insulin, resistin, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), von Willebrand factor (vWF), endothelin-1 (ET-1) and nitric oxide (NO) were measured. The homeostasis model assessment, insulin resistance index (HOMA-IR) was calculated. Patients were divided into two groups according to the median level of resistin. Cytokine levels and indicators of vascular endothelial function were compared. Multiple linear regression was used to determine factors influencing resistin.</p><p><b>RESULTS</b>Serum resistin ranged from 2.57 ng/ml to 20.18 ng/ml in hypertensive patients. High resistin group (> 8.36 ng/ml) had higher levels of TNF-α, IL-6, vWF and ET-1 but lower level of NO compared with low resistin group (P < 0.01). Resistin was positively correlated with body mass index, systolic blood pressure, HOMA-IR, low-density lipoprotein cholesterol, TNF-α and ET-1 but negatively correlated with NO (all P < 0.05). Multiple linear regression analysis revealed that HOMA-IR, TNF-α, NO and ET-1 are independent predictors of resistin with standardized regression coefficients of 0.625, 0.368, -0.260 and 0.222, respectively (all P < 0.01).</p><p><b>CONCLUSIONS</b>We conclude that higher resistin levels are associated with inflammatory activation and endothelial dysfunction, because patients with essential hypertension have increased TNF-α, IL-6, vWF and ET-1 and decreased NO. Moreover, the statistical association of resistin with TNF-α, NO and ET-1 suggests involvement of resistin in the progression of hypertension by influencing inflammation and endothelial function.</p>

Potential proarrhythmic effect of cardiac resynchronization therapy during perioperative period: data from a single cardiac center / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cardiac resynchronization therapy (CRT) could improve heart function, symptom status, quality of life and reduce hospitalization and mortality in patients with severe heart failure (HF) with optimal medical management. However, the possible adverse effects of CRT are often ignored by clinicians.</p><p><b>METHOD</b>A retrospective analysis of CRT over a 6-year period was made in a single cardiac center.</p><p><b>RESULTS</b>Fifty-four patients were treated with CRT(D) device, aged (57 ± 11) years, with left ventricular ejection fraction of (32.1 ± 9.8)%, of which 4 (7%) developed ventricular tachycardia/ventricular fibrillation (VT/VF) or junctional tachycardia after operation. Except for one with frequent ventricular premature beat before operation, the others had no previous history of ventricular arrhythmia. Of the 4 patients, 3 had dilated cardiomyopathy and 1 had ischemic cardiomyopathy, and tachycardia occurred within 3 days after operation. Sustained, refractory VT and subsequent VF occurred in one patient, frequent nonsustained VT in two patients and nonparoxysmal atrioventricular junctional tachycardia in one patient. VT was managed by amiodarone in two patients, amiodarone together with beta-blocker in one patient, and junctional tachycardia was terminated by overdrive pacing. During over 12-month follow-up, except for one patient's death due to refractory heart and respiratory failure in hospital, the others remain alive and arrhythmia-free.</p><p><b>CONCLUSIONS</b>New-onset VT/VF or junctional tachycardia may occur in a minority of patients with or without prior history of tachycardia after biventricular pacing. Arrhythmia can be managed by conventional therapy, but may require temporary discontinuation of pacing. More observational studies should be performed to determine the potential proarrhythmic effect of CRT.</p>

PPAR gamma agonist rosiglitazone alleviates hypoxia/reoxygenation-induced oxidative stress and apoptosis in rat cardiac myocytes / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effects of different concentrations of PPAR gamma agonist rosiglitazone on hypoxia/reoxygenation-induced oxidative stress, cell viability and apoptosis in rat cardiac myocytes.</p><p><b>METHODS</b>Cultured rat cardiac myocytes were divided into 5 groups, namely group I (normal group), group II (20 micromo/L ROS group), group III (I/R group), group IV (I/R+20 micromo/L ROS group), and group V (I/R+80 micromo/L ROS group). Group IV and group V were treated with rosiglitazone 12 h before hypoxia/reoxygenation. The changes in cell morphology were observed under optical and transmission electron microscopy, and levels of malondialdehyde (MDA), superoxide dismutase (SOD) activity, and lactate dehydrogenase (LDH) content were determined after the treatment. MTT assay was performed to assess the cell viability and flow cytometry was used to analyze the cell apoptosis.</p><p><b>RESULTS</b>Hypoxia/reoxygenation resulted in significantly increased MDA and LDH contents and apoptosis of the cardiac myocytes (P<0.05), but lowered SOD activity and the cell viability (P<0.05). The MDA and LDH contents and apoptotic rate were significantly lower but SOD content and cell vitality significantly higher in groups IV and V than in group III (P<0.05). Group V showed significantly lower MDA and LDH contents and apoptotic rate but higher but SOD content and cell vitality than group IV (P<0.05). Electron microscopy revealed obvious apoptotic changes in group III, and only mild changes were found in group V.</p><p><b>CONCLUSION</b>Rosiglitazone can significantly reduce hypoxia/reoxygenation-induced oxidative stress in cardiac myocytes, improve the cell viability and dose-dependently reduce the apoptotic rate of the cardiac myocytes.</p>

R25G mutation in exon 1 of LMNA gene is associated with dilated cardiomyopathy and limb-girdle muscular dystrophy 1B / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mutations of the LMNA gene encoding lamin A and C are associated with dilated cardiomyopathy (DCM), conduction system defects and skeletal muscle dystrophy. Here we report a family with a mutation of the LMNA gene to identify the relationship between genotype and phenotype.</p><p><b>METHODS</b>All 30 members of the family underwent clinical and genetic evaluation. A mutation analysis of the LMNA gene was performed. All of the 12 exons of LMNA gene were extended with polymerase chain reaction (PCR) and the PCR products were screened for gene mutation by direct sequencing.</p><p><b>RESULTS</b>Ten members of the family had limb-girdle muscular dystrophy (LGMD) and 6 are still alive. Two patients suffered from DCM. Cardiac arrhythmias included atrioventricular block and atrial fibrillation; sudden death occurred in 2 patients. The pattern of inheritance was autosomal dominant. Mutation c.73C > G (R25G) in exon 1 encoding the globular domains was confirmed in all of the affected members, resulting in the conversion of arginine (Arg) to glycine (Gly).</p><p><b>CONCLUSIONS</b>The mutation R25G in exon 1 of LMNA gene we reported here in a Chinese family had a phenotype of malignant arrhythmia and mild LGMD, suggesting that patients with familial DCM, conduction system defects and skeletal muscle dystrophy should be screened by genetic testing for the LMNA gene.</p>

Effects of oxidative stress on ventricular remodeling after myocardial infarction in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of oxidative stress on ventricular remodeling after acute myocardial infarction (AMI) in rats.</p><p><b>METHODS</b>AMI was induced in 20 SD rats by ligation of the anterior descending coronary artery, and another 12 rats without the ligation served as the sham-operated group. Six weeks after the operation, the heart mass index (HMI), left ventricular mass index (LVMI), right ventricular mass index (RVMI), the indexes of heart function, cardiac myocyte apoptosis index, collagen content and collagen I/III ratio and the indexes of oxidative stress were measured.</p><p><b>RESULTS</b>After AMI, HMI, LVMI and RVMI increased significantly (P<0.05), the heart function deteriorated significantly (P<0.01), and the cardiac myocyte apoptosis index in the non-infarct area, collagen content and collagen I/III ratio in the infarct and non-infarct areas were all significantly increased (P<0.05 or 0.01). Myocardial superoxide dismutase (SOD) activity was significantly lowered after AMI, which resulted in significantly increased myocardial malondialdehyde (MDA) level and decreased ratio of SOD/MDA (P<0.05). Correlations were found between the indexes of oxidative stress in myocardium, those of the heart function and those pertaining to ventricular remodeling after AMI.</p><p><b>CONCLUSION</b>Oxidative stress may be involved in ventricular remodeling after AMI, and antioxidants can be an option for treatment of ventricular remodeling.</p>

Blockades of angiotensin and aldosterone reduce osteopontin expression and interstitial fibrosis infiltration in rats with myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been reported that osteopontin has an important role in cardiac fibrosis and remodeling. However, its direct mechanisms remain unclear. The purpose of this study was to investigate the role of angiotensin and aldosterone blockades in cardiac osteopontin expression associated with cardiac remodeling in myocardial infarcted (MI) rats.</p><p><b>METHODS</b>Fifty SD rats that survived 24 hours after ligating left anterior descending coronary artery were randomly divided into three groups: MI-saline group (n = 15, 5 ml/d), MI-perindopril group (n = 18, perindopril 2 mgxkg(-1)d(-1)) and MI-spironolacton (n = 17, spironolacton 20 mgxkg(-1)xd(-1)). A sham operation group (n = 15) was selected as non-infarcted control. At 6 weeks after treatment, hemodynamic pararmeters and left ventricular function were measured with catheterization, interstitial fibrosis infiltration and cardiomyocyte diameters were evaluated histologically. Myocardium osteopontin protein expression level in the non-infarcted myocardium was detected by Western blotting.</p><p><b>RESULTS</b>No osteopontin protein was detected in the myocardium of sham-operation rats. High levels of osteopontin protein expression were detected in the MI-saline rats, but the levels were suppressed in the MI-perindopril and MI-spironolacton rats at 6 weeks following MI (P < 0.01, respectively). Compared with the sham operation group, all rats in the MI group showed marked interstitial fibrosis infiltration in the non-infarction area, higher ventricular weight/body weight ratio, significantly increased cardiomyocyte diameter (P < 0.01, respectively), and developed significant systolic and diastolic dysfunction as indicated by decreased left ventricular systolic pressure (LVSP) and +/-dp/dt, as well as increased left ventricular end-diastolic pressure (LVEDP) (P < 0.01, respectively). Angiotensin and aldosterone blockades partly prevented cardiac fibrosis and systolic and diastolic dysfunction (P < 0.01, respectively).</p><p><b>CONCLUSION</b>Treatment with angiotensin and aldosterone blockades inhibits expression of osteopontin in the non-infarcted myocardium and prevents cardiac remodeling following MI.</p>

Association of angiotensin I-converting enzyme gene polymorphism with ACE and PAI-1 levels in Guangdong Chinese Han patients with essential hypertension / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the association between angiotensin I-converting enzyme (ACE) gene and the levels of ACE and PAI-1 in Chinese Han patients with essential hypertension (EH) in Guangdong Province.</p><p><b>METHODS</b>Polymerase chain reaction was used to examine the ACE genotype, colorimetry used to measure the serum ACE level, and spectrophotometric assay performed to examine the plasma PAI-1 level in 115 EH patients and 96 healthy controls in Guangdong Province.</p><p><b>RESULTS</b>The ACE DD genotype and D allele frequencies were significantly higher in EH group than in the control group (P<0.05), and the EH patients also had significantly higher serum ACE level and plasma PAI-1 level than the control subjects (P<0.01). The serum ACE level was positively correlated with plasma PAI-1 level in both EH group and control group (r=0.7913 and 0.7806, respectively, P<0.01). In EH group, the patients with DD genotype showed significantly higher serum ACE and plasma PAI-1 levels than those with ID and II genotypes (P<0.01), and patients with ID genotype had significantly higher ACE and PAI-1 levels than those with II genotype (P<0.05).</p><p><b>CONCLUSION</b>The DD genotype and D allele of ACE gene can be risk factors for essential hypertension in Chinese Han subjects in Guangdong Province, and the EH patients have elevated serum ACE and plasma PAI-1 levels. Increased ACE level due to DD polymorphism may play an important role in elevating plasma PAI-1 level. The genetic variation of ACE contributes to the balance of fibrinolytic pathway, which may be one of the pathological mechanisms linking the ACE I/D genotype and EH.</p>

Effects of perindopril on left ventricular remodeling and myocardial osteopontin expression in rats with myocardial infarction / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effects of perindopril on left ventricular remodeling and myocardial osteopontin expression in rats with myocardial infarction (MI).</p><p><b>METHODS</b>Male adult SD rats were randomly divided into sham-operation group, MI-saline group and MI-perindopril group, and in the latter two groups, ligation of the left anterior descending artery was performed to establish rat models of myocardial infarction and perindopril (2 mg/kg daily) or saline was administered since the next day of MI. Four weeks later, the left ventricular diameter (LVEDD and LVESD) and left ventricular ejection fraction were estimated with echocardiography, and the left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and -/+dp/dt(max) was obtained via hemodynamic measurement, with also evaluation of the cardiac myocyte diameter and interstitial fibrosis infiltration with histological methods. Western blotting was performed to detect the expression level of myocardium osteopontin protein.</p><p><b>RESULTS</b>Compared with the sham-operation group, all MI rats developed significant systolic and diastolic dysfunction, as indicated by decreased LVEF, LVSP and -/+dp/dt(max), as well as increased LVEDP. MI rats showed significantly dilated left ventricles and higher ventricular weight/body weight ratio, significantly increased cardiomyocyte diameter and marked interstitial fibrosis in the non-infarction area. Perindopril treatment partially prevented cardiac dysfunction and left ventricular remodeling as indicated by the above indices. No osteopontin was detected in the myocardium of sham-operation rats, and in MI rats, high level of osteopontin expression, as detected in MI-saline group, was significantly inhibited by perindopril treatment.</p><p><b>CONCLUSION</b>Perindopril treatment can significantly inhibit left ventricular remodeling and myocardium osteopontin expression in rats with MI.</p>

Effects of Probucol on Expression of Bcl-2,Bax and Oxidative Stress in Myocardial Infarcted Rats / 中华高血压杂志

Background Cardiomyocytes apoptosis was related to oxidative stress which has been shown to play an important role in ventricular remodeling after myocardial infarction(MI).Probucol is a hypolipidemic and antioxidant agents.Several reports demonstrated its cardioprotective effect after MI.However,the exact effect of probucol on the modification of the apoptosis related gene Bcl-2 and Bax is not clear.Objective To investigate the effects of probucol on mRNA and protein expression of Bcl-2,Bax and oxidative stress in myocardial infarcted rats.Methods Forty-one SD rats that survived 24 h after ligating left anterior descending coronary artery were randomly to receive placebo-saline(5 mL/d,n=20)or probucol(probucol 60 mg/kg?d,n=21).Twelve rats underwent sham operation were served as control(n=12).Six weeks after treatment,hemodynamic pararmeters and left ventricular function were measured with catheterization.Cardiomyocytes apoptosis were determined by TUNEL method.Myocardium mRNA of Bcl-2 and Bax expression levels in the non-infarcted myocardium were as- sessed by RT-PCR.The myocardium protein expression of Bcl-2 and Bax in the non-infarcted myocardium were de- termined by Western blot.Colorimetry was used to determine oxidative metabolism index in myocardium.Results 1)Compared with the sham rats,all MI rats showed marked decrease in Bcl-2 mRNA and protein expression in myo- cardium with increase of Bax mRNA and protein expression and apoptosis index(P