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《循环》 2009年3月31日

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1.Arrhythmia/Electrophysiology

Molecular Architecture of the Human Sinus Node
Insights Into the Function of the Cardiac Pacemaker

Background— Although we know much about the molecular makeup of the sinus node (SN) in small mammals, little is known about it in humans. The aims of the present study were to investigate the expression of ion channels in the human SN and to use the data to predict electrical activity.

Methods and Results— Quantitative polymerase chain reaction, in situ hybridization, and immunofluorescence were used to analyze 6 human tissue samples. Messenger RNA (mRNA) for 120 ion channels (and some related proteins) was measured in the SN, a novel paranodal area, and the right atrium (RA). The results showed, for example, that in the SN compared with the RA, there was a lower expression of Nav1.5, Kv4.3, Kv1.5, ERG, Kir2.1, Kir6.2, RyR2, SERCA2a, Cx40, and Cx43 mRNAs but a higher expression of Cav1.3, Cav3.1, HCN1, and HCN4 mRNAs. The expression pattern of many ion channels in the paranodal area was intermediate between that of the SN and RA; however, compared with the SN and RA, the paranodal area showed greater expression of Kv4.2, Kir6.1, TASK1, SK2, and MiRP2. Expression of ion channel proteins was in agreement with expression of the corresponding mRNAs. The levels of mRNA in the SN, as a percentage of those in the RA, were used to estimate conductances of key ionic currents as a percentage of those in a mathematical model of human atrial action potential. The resulting SN model successfully produced pacemaking.

Conclusions— Ion channels show a complex and heterogeneous pattern of expression in the SN, paranodal area, and RA in humans, and the expression pattern is appropriate to explain pacemaking.

2. Arrhythmia/Electrophysiology

Funny Current Downregulation and Sinus Node Dysfunction Associated With Atrial Tachyarrhythmia
A Molecular Basis for Tachycardia-Bradycardia Syndrome

Background— Sinoatrial node (SAN) dysfunction is frequently associated with atrial tachyarrhythmias (ATs). Abnormalities in SAN pacemaker function after termination of ATs can cause syncope and require pacemaker implantation, but underlying mechanisms remain poorly understood. This study examined the hypothesis that ATs impair SAN function by altering ion channel expression.

Methods and Results— SAN tissues were obtained from 28 control dogs and 31 dogs with 7-day atrial tachypacing (400 bpm). Ionic currents were measured from single SAN cells with whole-cell patch-clamp techniques. Atrial tachypacing increased SAN recovery time in vivo by 70% (P<0.01), a change which reflects impaired SAN function. In dogs that underwent atrial tachypacing, SAN mRNA expression (real-time reverse-transcription polymerase chain reaction) was reduced for hyperpolarization-activated cyclic nucleotide-gated subunits (HCN2 and HCN4) by >50% (P<0.01) and for the β-subunit minK by 42% (P<0.05). SAN transcript expression for the rapid delayed-rectifier (IKr) -subunit ERG, the slow delayed-rectifier (IKs) -subunit KvLQT1, the β-subunit MiRP1, the L-type (ICaL) and T-type (ICaT) Ca2+-current subunits Cav1.2 and Cav3.1, and the gap-junction subunit connexin 43 (were unaffected by atrial tachypacing. Atrial tachypacing reduced densities of the HCN-related funny current (If) and IKs by 48% (P<0.001) and 34% (P<0.01), respectively, with no change in voltage dependence or kinetics. IKr, ICaL, and ICaT were unaffected. SAN cells lacked Ba2+-sensitive inward-rectifier currents, irrespective of AT. SAN action potential simulations that incorporated AT-induced alterations in If accounted for slowing of periodicity, with no additional contribution from changes in IKs.

Conclusions— AT downregulates SAN HCN2/4 and minK subunit expression, along with the corresponding currents If and IKs. Tachycardia-induced remodeling of SAN ion channel expression, particularly for the "pacemaker" subunit If, may contribute to the clinically significant association between SAN dysfunction and supraventricular tachyarrhythmias.

3.Epidemiology

Pericardial Fat, Intrathoracic Fat, and Measures of Left Ventricular Structure and Function
The Framingham Heart Study

Background— Pericardial fat has been implicated in the pathogenesis of obesity-related cardiovascular disease. Whether the associations of pericardial fat and measures of cardiac structure and function are independent of the systemic effects of obesity and visceral adiposity has not been fully explored.

Methods and Results— Participants from the Framingham Heart Study (n=997; 54.4% women) underwent chest and abdominal computed tomography and cardiovascular magnetic resonance imaging between 2002 and 2005. Pericardial fat, intrathoracic fat, and visceral adipose tissue quantified from multidetector computed tomography, along with body mass index and waist circumference, were examined in relation to cardiovascular magnetic resonance measures of left ventricular (LV) mass, LV end-diastolic volume, and left atrial dimension. In women, pericardial fat (r=0.20 to 0.35, P<0.001), intrathoracic fat (r=0.25 to 0.37, P<0.001), visceral adipose tissue (r=0.24 to 0.45, P<0.001), body mass index (r=0.36 to 0.53, P<0.001), and waist circumference (r=0.30 to 0.48, P<0.001) were directly correlated with LV mass, LV end-diastolic volume, and left atrial dimension. In men, pericardial fat (r=0.19 to 0.37, P<0.001), intrathoracic fat (r=0.17 to 0.31, P<0.001), visceral adipose tissue (r=0.19 to 0.36, P<0.001), body mass index (r=0.32 to 0.44, P<0.001), and waist circumference (r=0.34 to 0.44, P<0.001) were directly correlated with LV mass and left atrial dimension, but LV end-diastolic volume was not consistently associated with adiposity measures. Associations persisted after multivariable adjustment but not after additional adjustment for body weight and visceral adipose tissue, except for pericardial fat and left atrial dimension in men.

Conclusions— Pericardial fat is correlated with cardiovascular magnetic resonance measures, but the association is not independent of or stronger than other ectopic fat stores or proxy measures of visceral adiposity. An important exception is left atrial dimension in men. These results suggest that the systemic effects of obesity on cardiac structure and function may outweigh the local pathogenic effects of pericardial fat.

4.Epidemiology

Plasma Asymmetric Dimethylarginine and Incidence of Cardiovascular Disease and Death in the Community

Background— Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, induces endothelial dysfunction. Although elevated ADMA has been associated with an increased risk of cardiovascular disease events and death in referral samples, the prognostic significance of ADMA in the community has not been adequately evaluated.

Methods and Results— We related plasma ADMA, L-arginine (Arg), and the ratio of Arg to ADMA to the incidence of cardiovascular disease (fatal or nonfatal myocardial infarction, coronary insufficiency, angina pectoris, stroke or transient ischemic attack, intermittent claudication, or heart failure) and death in 3320 Framingham Offspring Study participants (1769 women; mean age, 59 years). Over a follow-up period of 10.9 years, 281 individuals of 2956 free of cardiovascular disease at baseline developed incident cardiovascular disease, and 285 participants died. In multivariable models adjusting for established risk factors and other biomarkers (B-type natriuretic peptide, renin, homocysteine, urine albumin excretion, and C-reactive protein), ADMA and the ratio of Arg to ADMA were significantly associated with all-cause mortality (adjusted-hazard ratio [HR] per 1-SD increment, 1.21; 95% CI, 1.07 to 1.37; and HR per 1-SD increment, 0.80; 95% CI, 0.69 to 0.93, respectively), whereas Arg was not (HR per 1-SD increment, 0.89; 95% CI, 0.77 to 1.02). We noted effect modification by diabetes status; ADMA was associated with death in individuals without diabetes (adjusted HR per 1-SD increment, 1.30; 95% CI, 1.13 to 1.50) but not in individuals with diabetes (adjusted HR per 1-SD increment, 0.85; 95% CI, 0.62 to 1.16). ADMA, Arg, and the ratio of Arg to ADMA were not associated with cardiovascular disease incidence (P>0.10).

Conclusions— In our large community-based sample, ADMA was significantly associated with all-cause mortality, particularly in nondiabetic individuals.

5.Exercise Physiology

Effects of Different Types of Exercise Training Followed by Detraining on Endothelium-Dependent Dilation in Patients With Recent Myocardial Infarction

Background— In coronary artery disease, exercise training (ET) is associated with an improvement in endothelial function, but little is known about the relative effect of different types of training. The purpose of this study was to prospectively evaluate the effect of different types of ET on endothelial function in 209 patients after a first recent acute myocardial infarction.

Methods and Results— Endothelial function was evaluated before and after 4 weeks of different types of ET and after 1 month of detraining by measuring flow-mediated dilation and von Willebrand factor levels at baseline and after ET. Patients were randomized into 4 groups: group 1, aerobic ET (n=52); group 2, resistance training (n=54); group 3, resistance plus aerobic training (n=53); and group 4, no training (n=50). At baseline, flow-mediated dilation was 4.5±2.6% in group 1, 4.01±1.6% in group 2, 4.4±4% in group 3, and 4.3±2.3% in group 4 (P=NS). After ET, flow-mediated dilation increased to 9.9±2.5% in group 1, 10.1±2.6% in group 2, and 10.8±3% in group 3 (P<0.01 versus baseline for all groups); it also increased in group 4 but to a much lesser extent (to 5.1±2.5%; P<0.01 versus trained groups). The von Willebrand factor level after ET decreased by 16% (P<0.01) similarly in groups 1, 2, and 3 but remained unchanged in group 4. Detraining returned flow-mediated dilation to baseline levels (P<0.01 versus posttraining).

Conclusion— In patients with recent acute myocardial infarction, ET was associated with improved endothelial function independently of the type of training, but this effect disappeared after 1 month of detraining.

6.Health Services and Outcomes Research

A Statewide Collaborative Initiative to Improve the Quality of Care for Patients With Acute Myocardial Infarction and Heart Failure

Background— To enhance quality improvement, we created a unique statewide collaboration among 3 organizations: the Virginia Health Quality Center (Virginia’s Medicare Quality Improvement Organization), the American College of Cardiology, and the American Heart Association. The goal was to improve discharge measures for acute myocardial infarction and heart failure.

Methods and Results— In 2004, 29 hospitals participated in the collaborative initiative. Using Medicare data submitted from 2004 through the second quarter of 2006, we analyzed adherence to individual discharge measures and all-or-none appropriate care measures for acute myocardial infarction, heart failure, and both. To control for differences in hospital characteristics, we were able to match 21 of the participating hospitals with 21 similar nonparticipating hospitals. In this paired analysis, the total appropriate care measure increased from 61% to 77% in participating hospitals compared with an increase from 51% to 60% in nonparticipating hospitals (P<0.0001). A generalized linear mixed model examining the full data set at the patient level failed to show a clear advantage among participating hospitals. Participating hospitals had higher baseline rates for most quality measures, suggesting a possible effect of a prior collaborative. Further analysis of only hospitals that participated in a prior collaborative showed that participants in the current collaborative initiative had higher rates of improvement for 7 of 10 quality measures and appropriate care measures for heart failure, acute myocardial infarction, or both (all P<0.05).

Conclusions— We report a unique collaboration of a Medicare Quality Improvement Organization and 2 national organizations to address quality of care for acute myocardial infarction and heart failure. A composite measure of quality (the total appropriate care measure) improved more in the participating hospitals during the timeframe of the intervention, although the greater improvement in this and other measures in the participating hospitals appeared to be dependent on participation in a prior collaborative initiative.

7.Heart Failure

Randomized Trial of Warfarin, Aspirin, and Clopidogrel in Patients With Chronic Heart Failure
The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) Trial

Background— Chronic heart failure remains a major cause of mortality and morbidity. The role of antithrombotic therapy in patients with chronic heart failure has long been debated. The objective of this study was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm.

Methods and Results— This prospective, randomized clinical trial of open-label warfarin (target international normalized ratio of 2.5 to 3.0) and double-blind treatment with either aspirin (162 mg once daily) or clopidogrel (75 mg once daily) had a 30-month enrollment period and a minimum of 12 months of treatment. We enrolled 1587 men and women 18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of 35%. The primary outcome was the time to first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke. For the primary composite end point, the hazard ratios were as follows: for warfarin versus aspirin, 0.98 (95% CI, 0.86 to 1.12; P=0.77); for clopidogrel versus aspirin, 1.08 (95% CI, 0.83 to 1.40; P=0.57); and for warfarin versus clopidogrel, 0.89 (95% CI, 0.68 to 1.16; P=0.39). Warfarin was associated with fewer nonfatal strokes than aspirin or clopidogrel. Hospitalization for worsening heart failure occurred in 116 (22.2%), 97 (18.5%), and 89 (16.5%) patients treated with aspirin, clopidogrel, and warfarin, respectively (P=0.02 for warfarin versus aspirin).

Conclusion— The primary outcome measure and the mortality data do not support the primary hypotheses that warfarin is superior to aspirin and that clopidogrel is superior to aspirin.

8.Hypertension

Effect of Sulfaphenazole on Tissue Plasminogen Activator Release in Normotensive Subjects and Hypertensive Patients

Background— A nitric oxide–independent response, possibly mediated by hyperpolarization, regulates vascular tone, acting as a compensatory mechanism in the presence of impaired nitric oxide availability. Cytochrome P450 2C9 (CYP 2C9) is a source of endothelium-derived hyperpolarizing factors and modulates tissue-type plasminogen activator (tPA) release from endothelial cells; however, no effect of hyperpolarization on fibrinolysis has been documented in humans. We aimed to assess the effect of sulfaphenazole, a specific CYP 2C9 inhibitor, on tPA release in normotensive subjects and patients with essential hypertension.

Methods and Results— tPA release was measured in the forearm microcirculation of 56 normotensivesubjects and 57 patients with essential hypertension after bradykinin (0.015 µg · 100 mL–1 · min–1) and acetylcholine (1.5 µg · 100 mL–1 · min–1) infusions, with or without sulfaphenazole (0.03 µg · 100 mL–1 · min–1). Bradykinin and acetylcholine infusions were repeated with NG-monomethyl-L-arginine (L-NMMA; 100 µg · 100 mL–1 · min–1) and/or sulfaphenazole. tPA release by bradykinin and acetylcholine was higher in normotensive subjects than in patients with essential hypertension (P<0.01). Sulfaphenazole (P<0.01) blunted bradykinin-induced but not acetylcholine-induced tPA release in both groups. In normotensive subjects, L-NMMA infusion reduced tPA release (P<0.01). When L-NMMA was coinfused with sulfaphenazole, tPA release induced by bradykinin, but not by acetylcholine, was further reduced (P<0.01). In patients with essential hypertension, tPA release by both agonists was unaffected by L-NMMA, but only bradykinin-induced tPA release was blunted by sulfaphenazole, alone or with L-NMMA (P<001).

Conclusions— Sulfaphenazole inhibits bradykinin-induced tPA release, which suggests a modulatory role of CYP 2C9–derived endothelium-derived hyperpolarizing factors in tPA release in humans. In patients with essential hypertension, tPA release depends exclusively on endothelium-derived hyperpolarizing factor, which is an ineffective compensatory mechanism in the presence of impaired nitric oxide availability.

9.Interventional Cardiology

Safety of Short-Term Discontinuation of Antiplatelet Therapy in Patients With Drug-Eluting Stents

Background— Antiplatelet therapy is often discontinued in patients with drug-eluting stents who are undergoing surgical procedures. However, discontinuation of antiplatelet therapy is an important risk factor for late stent thrombosis. Our objective was to examine the safety of short-term discontinuation of antiplatelet therapy.

Methods and Results— We systematically searched Medline for reported cases of late stent thrombosis and very late stent thrombosis published between January 2001 and July 2008. We restricted our search to Academic Research Consortium–defined definite cases. We identified 161 cases of late stent thrombosis or very late stent thrombosis from 84 articles (79 from case reports, 61 from registries, and 21 from randomized clinical trials). Patients had a mean age of 58.4±13.4 years, and 88% were male. A total of 19 cases occurred in patients who were receiving dual antiplatelet therapy at the time of the event. If patients stopped both antiplatelet agents simultaneously, the median time to event was 7 days. If patients had previously stopped a thienopyridine with no ill effect and subsequently stopped acetylsalicylic acid, the median time to event was also 7 days from the time of acetylsalicylic acid cessation. If the thienopyridine was stopped but acetylsalicylic acid was maintained, the median time to event was 122 days. Among the 48 patients who stopped both agents, 36 cases (75%) occurred within 10 days. Among the 94 patients who discontinued a thienopyridine but continued acetylsalicylic acid, only 6 cases (6%) occurred within 10 days.

Conclusion— If acetylsalicylic acid therapy is maintained, short-term discontinuation of a thienopyridine may be relatively safe in patients with drug-eluting stents.

10.Molecular Cardiology

Resveratrol Prevents the Prohypertrophic Effects of Oxidative Stress on LKB1

Background— Master regulators of protein synthesis such as mammalian target of rapamycin (mTOR) and p70S6 kinase contribute to left ventricular hypertrophy. These prohypertrophic pathways are modulated by a number of kinase cascades, including the hierarchical LKB1/AMP-activated protein kinase (AMPK) energy-sensing pathway. Because oxidative stress inhibits the LKB1/AMPK signaling axis to promote abnormal cell growth in cancer cells, we investigated whether oxidative stress associated with hypertension also results in the inhibition of this kinase circuit to contribute to left ventricular hypertrophy.

Methods and Results— In the spontaneously hypertensive rat, a well-established genetic model of hypertension and subsequent cardiac hypertrophy, the development of left ventricular hypertrophy is associated with an increase in the electrophilic lipid peroxidation byproduct 4-hydroxy-2-nonenal (HNE). Using isolated cardiomyocytes, we show that elevated levels of HNE result in the formation of HNE-LKB1 adducts that inhibit LKB1 and subsequent AMPK activity. Consistent with inhibition of the LKB1/AMPK signaling pathway, the mTOR/p70S6 kinase system is activated, which is permissive for cardiac myocyte cell growth. Treatment of cardiomyocytes with resveratrol prevents HNE modification of the LKB1/AMPK signaling axis and blunts the prohypertrophic p70S6 kinase response. Furthermore, administration of resveratrol to spontaneously hypertensive rats results in increased AMPK phosphorylation and activity and reduced left ventricular hypertrophy.

Conclusions— Our data identify a molecular mechanism in the cardiomyocyte involving the oxidative stress–derived lipid peroxidation byproduct HNE and the LKB1/AMPK signaling pathway that contributes to the development of left ventricular hypertrophy. We also suggest that resveratrol may be a potential therapy for patients at risk for developing pathological cardiac hypertrophy by preventing this prohypertrophic process.

11.Valvular Heart Disease

Detoxification and Endothelialization of Glutaraldehyde-Fixed Bovine Pericardium With Titanium Coating
A New Technology for Cardiovascular Tissue Engineering

Background— Endothelial cell seeding of glutardialdehyde-fixed biological heart valves is hypothesized to improve biocompatibility and durability; however, the toxicity of glutardialdehyde prevents its use as a biological coating. Therefore, different detoxification strategies are applied, including surface coating with titanium, before in vitro endothelialization of glutaraldehyde-fixed bovine pericardium as the base material for prosthetic heart valves.

Methods and Results— Bovine pericardium was fixed with 0.25% glutardialdehyde. Detoxification was performed with citric acid, aldehyde dehydrogenase, and plasma deposition with titanium at low temperatures of 30°C to 35°C. Toxic glutaraldehyde ligands were quantified photometrically, and the vitality of seeded cells was tested to validate detoxification methods. Detoxification agents and titanium coating were applied before seeding with human endothelial cells. Endothelial cells were visualized by electron microscopic surface scanning. To evaluate cell adhesion, shear stress was applied by a flow of 5 L/min over 24 hours. Compared with untreated glutaraldehyde-fixed samples, treatment with the different agents reduced free aldehyde groups gradually (citric acid 5% < citric acid 10% < titanium < aldehyde dehydrogenase). A combination of citric acid 10%, aldehyde dehydrogenase, and titanium coating resulted in a reduction of free aldehyde ligands to 17.3±4.6% (P0.05) and demonstrated a vitality of seeded cells of 94±6.7% (P0.05). This procedure yielded a completely confluent layer of regular human endothelial cells (n=5). After application of shear stress for 24 hours on these endothelial layers, cell vitality was 81%.

Conclusions— Titanium coating combined with chemical procedures yielded significant detoxification and complete endothelialization of conventional glutaraldehyde-fixed pericardium. This new technique might improve glutardialdehyde-fixed cardiovascular bioimplants for better biocompatibility and longer durability.

12.Vascular Medicine

Local Inflammation and Hypoxia Abolish the Protective Anticontractile Properties of Perivascular Fat in Obese Patients

Background— Inflammation in adipose tissue has been implicated in vascular dysfunction, but the local mechanisms by which this occurs are unknown.

Methods and Results— Small arteries with and without perivascular adipose tissue were taken from subcutaneous gluteal fat biopsy samples and studied with wire myography and immunohistochemistry. We established that healthy adipose tissue around human small arteries secretes factors that influence vasodilation by increasing nitric oxide bioavailability. However, in perivascular fat from obese subjects with metabolic syndrome (waist circumference 111±2.8 versus 91.1±3.5 cm in control subjects, P<0.001; insulin sensitivity 41±5.9% versus 121±18.6% in control subjects, P<0.001), the loss of this dilator effect was accompanied by an increase in adipocyte area (1786±346 versus 673±60 µm2, P<0.01) and immunohistochemical evidence of inflammation (tumor necrosis factor receptor 1 12.4±1.1% versus 6.7±1%, P<0.001). Application of the cytokines tumor necrosis factor receptor- and interleukin-6 to perivascular fat around healthy blood vessels reduced dilator activity, resulting in the obese phenotype. These effects could be reversed with free radical scavengers or cytokine antagonists. Similarly, induction of hypoxia stimulated inflammation and resulted in loss of anticontractile capacity, which could be rescued by catalase and superoxide dismutase or cytokine antagonists. Incubation with a soluble fragment of adiponectin type 1 receptor or inhibition of nitric oxide synthase blocked the vasodilator effect of healthy perivascular adipose tissue.

Conclusions— We conclude that adipocytes secrete adiponectin and provide the first functional evidence that it is a physiological modulator of local vascular tone by increasing nitric oxide bioavailability. This capacity is lost in obesity by the development of adipocyte hypertrophy, leading to hypoxia, inflammation, and oxidative stress.

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2009-03-31 07:15 浏览 : 3108 回复 : 23

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浅浅阳光编辑于 2009-05-03 18:39

• 临床要不要去做超声，超声科待遇怎么样？

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1. Molecular Architecture of the Human Sinus Node
人类窦房结的分子构成

Background— Although we know much about the molecular makeup of the sinus node (SN) in small mammals, little is known about it in humans. The aims of the present study were to investigate the expression of ion channels in the human SN and to use the data to predict electrical activity.
背景：尽管我们对小型哺乳动物窦房结的分子组成有了一定的了解，但是对人类窦房结的分子组成却知之甚少。本研究的目的即了解人类窦房结离子通道的表达并应用这些数据来预测其电活动。

Methods and Results— Quantitative polymerase chain reaction, in situ hybridization, and immunofluorescence were used to analyze 6 human tissue samples. Messenger RNA (mRNA) for 120 ion channels (and some related proteins) was measured in the SN, a novel paranodal area, and the right atrium (RA). The results showed, for example, that in the SN compared with the RA, there was a lower expression of Nav1.5, Kv4.3, Kv1.5, ERG, Kir2.1, Kir6.2, RyR2, SERCA2a, Cx40, and Cx43 mRNAs but a higher expression of Cav1.3, Cav3.1, HCN1, and HCN4 mRNAs. The expression pattern of many ion channels in the paranodal area was intermediate between that of the SN and RA; however, compared with the SN and RA, the paranodal area showed greater expression of Kv4.2, Kir6.1, TASK1, SK2, and MiRP2. Expression of ion channel proteins was in agreement with expression of the corresponding mRNAs. The levels of mRNA in the SN, as a percentage of those in the RA, were used to estimate conductances of key ionic currents as a percentage of those in a mathematical model of human atrial action potential. The resulting SN model successfully produced pacemaking.
方法与结果：我们应用定量PCR、原位杂交和免疫荧光技术分析了6个人类组织标本，测定了窦房结区、窦房结周围区以及右心房区120种离子通道相应mRNA和某些相关蛋白的表达。结果显示，与右心房区相比，窦房结区Nav1.5、Kv4.3、Kv1.5、ERG、Kir2.1、Kir6.2、RyR2、SERCA2a、Cx40以及Cx43的mRNAs表达减低，Cav1.3、Cav3.1、HCN1和HCN4的mRNAs表达增加。而窦房结周围区一些离子通道的表达则介于窦房结区和右心房区表达水平之间；但是Kv4.2、Kir6.1、TASK1、SK2和MiRP2在窦房结周围区的表达却显著高于窦房结区和右心房区。离子通道蛋白的表达与相应mRNA的表达一致。窦房结区mRNA的表达水平，与右心房区mRNA的表达水平一样，均在构建人类心房功能的数学模型中用于评估关键离子通道电流的大小。而应用这些结果所构建的窦房结模型，成功的实现了自主节律。

Conclusions— Ion channels show a complex and heterogeneous pattern of expression in the SN, paranodal area, and RA in humans, and the expression pattern is appropriate to explain pacemaking.
结论：离子通道在窦房结区、窦房结周围区以及右心房区的表达不仅复杂而且差异性较大，而这一表达的差异性却恰恰可以解释自主节律的产生机制。

人类窦房结的分子构成
背景：尽管我们对小型哺乳动物窦房结的分子组成有了一定的了解，但是对人类窦房结的分子组成却知之甚少。本研究的目的即了解人类窦房结离子通道的表达并应用这些数据来预测其电活动。
方法与结果：我们应用定量PCR、原位杂交和免疫荧光技术分析了6个人类组织标本，测定了窦房结区、窦房结周围区以及右心房区120种离子通道相应mRNA和某些相关蛋白的表达。结果显示，与右心房区相比，窦房结区Nav1.5、Kv4.3、Kv1.5、ERG、Kir2.1、Kir6.2、RyR2、SERCA2a、Cx40以及Cx43的mRNAs表达减低，Cav1.3、Cav3.1、HCN1和HCN4的mRNAs表达增加。而窦房结周围区一些离子通道的表达则介于窦房结区和右心房区表达水平之间；但是Kv4.2、Kir6.1、TASK1、SK2和MiRP2在窦房结周围区的表达却显著高于窦房结区和右心房区。离子通道蛋白的表达与相应mRNA的表达一致。窦房结区mRNA的表达水平，与右心房区mRNA的表达水平一样，均在构建人类心房功能的数学模型中用于评估关键离子通道电流的大小。而应用这些结果所构建的窦房结模型，成功的实现了自主节律。
结论：离子通道在窦房结区、窦房结周围区以及右心房区的表达不仅复杂而且差异性较大，而这一表达的差异性却恰恰可以解释自主节律的产生机制。

2009-03-31 08:04

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• 科技部通报李红良、饶毅教授、曹雪涛院士等有关论文涉嫌造假处理情况

武功再高也怕菜刀

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7.Heart Failure

Randomized Trial of Warfarin, Aspirin, and Clopidogrel in Patients With Chronic Heart Failure
The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) Trial
慢性心衰病人服用华法林，阿司匹林，氯吡格雷效果的随机试验：
华法林和抗血小板药物治疗慢性心衰的随机试验(WATCH)

Background— Chronic heart failure remains a major cause of mortality and morbidity.
背景——慢性心衰是导致死亡和发病的主要原因。

The role of antithrombotic therapy in patients with chronic heart failure has long been debated.
慢性心衰病人进行抗凝血治疗以来一直存在争议。

The objective of this study was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm.
本研究的目的是探讨窦性节律伴射血分数减少的心衰病人使用何种抗血栓药物效果最为理想。

Methods and Results— This prospective, randomized clinical trial of open-label warfarin (target international normalized ratio of 2.5 to 3.0) and double-blind treatment with either aspirin (162 mg once daily) or clopidogrel (75 mg once daily) had a 30-month enrollment period and a minimum of 12 months of treatment.
方法和结果：
本项前瞻性的随机临床试验登记注册期为期30个月，在华法林（国际标准化比率2.5到3.0）治疗的基础上，采用双盲法随机给予阿司匹林(每日一次162mg)或氯吡格雷(每日一次75mg)，治疗至少维持12个月。

We enrolled 1587 men and women 18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of 35%.
我们入选1587名18岁的男性和女性病人参加实验，他们出现心衰症状至少有3个月，而且为窦性心律，左室射血分数仅有35%。

The primary outcome was the time to first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke.
主要的结果是首次非致命性心肌梗塞，非致命中风或死亡。

For the primary composite end point, the hazard ratios were as follows: for warfarin versus aspirin, 0.98 (95% CI, 0.86 to 1.12; P=0.77); for clopidogrel versus aspirin, 1.08 (95% CI, 0.83 to 1.40; P=0.57); and for warfarin versus clopidogrel, 0.89 (95% CI, 0.68 to 1.16; P=0.39).
对于主要复合终点事件,危害比如下：华法林比阿司匹林为0.98 (95% 的可信区间 0.86 to 1.12; P=0.77); 氯吡格雷比阿司匹林为1.08 (95%的可信区间 0.83 to 1.40; P=0.57);华法林比氯吡格雷为0.89 (95%可信区间, 0.68 to 1.16; P=0.39)。

Warfarin was associated with fewer nonfatal strokes than aspirin or clopidogrel. Hospitalization for worsening heart failure occurred in 116 (22.2%), 97 (18.5%), and 89 (16.5%) patients treated with aspirin, clopidogrel, and warfarin, respectively (P=0.02 for warfarin versus aspirin).
与阿司匹林和氯吡格雷相比，华法林与非致命性中风的相关性较小。因心衰恶化而需住院治疗的比例，使用阿司匹林的病人有116个（22.2%），使用氯吡格雷的病人有97个（18.5%），使用华法林的病人89个（16.5%），华法林与阿司匹林之间没有显著差异（P=0.02）

Conclusion— The primary outcome measure and the mortality data do not support the primary hypotheses that warfarin is superior to aspirin and that clopidogrel is superior to aspirin.
结论：主要事件和死亡率数据并不支持以往华法林优于阿司匹林，氯吡格雷优于阿司匹林的假设。

2009-03-31 08:18

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武功再高也怕菜刀编辑于 2009-04-01 09:00

• #医生的昵称有多好笑#这是你们热爱工作的表现吗？哈哈哈哈

houliping

丁香园准中级站友

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认领4.Epidemiology

Plasma Asymmetric Dimethylarginine and Incidence of Cardiovascular Disease and Death in the Community

2009-03-31 08:44

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• 医生在抢救手术失败后会是什么感觉？

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《循环》 2009年3月31日

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