发帖
每发1个新帖
可以获得0.5个丁当奖励
回帖

Circulation 2009年9月22日

只看楼主
页码直达：
直达末页

楼主

铁杆站友

+1 积分
1楼

这个帖子发布于11年零126天前，其中的信息可能已发生改变或有所发展。

Abstract 1 of 12 (Circulation. 2009;120:1029-1035.)
© 2009 American Heart Association, Inc.

--------------------------------------------------------------------------------

Arrhythmia/Electrophysiology

The First Evaluation of a Novel Vitamin K Antagonist, Tecarfarin (ATI-5923), in Patients With Atrial Fibrillation

Background— Tecarfarin (ATI-5923) is a novel oral vitamin K antagonist. Unlike warfarin, it is metabolized by esterases, escaping metabolism by the cytochrome P450 system and thereby avoiding cytochrome P450–mediated drug-drug or drug-food interactions as well as genetic variations found in the cytochrome P450 system. Both tecarfarin and warfarin can be monitored with the international normalized ratio. We hypothesized that the time in therapeutic range for tecarfarin will exceed values usually experienced with warfarin.

Methods and Results— This was a 6- to 12-week open-label, multicenter, phase IIA study of 66 atrial fibrillation patients with a mild to moderate risk of stroke to determine the safety and tolerability of tecarfarin and to ascertain an optimal tecarfarin dosing regimen. Sixty-four subjects (97%) were taking warfarin at enrollment and were switched to tecarfarin. After the initial 3 weeks of tecarfarin treatment, the mean interpolated time in therapeutic range was 71.4%. Only 10.9% of patients had time in therapeutic range of <45%. Times in extreme international normalized ratio ranges of <1.5 and >4.0 were 1.2% and 1.2%, respectively. The median daily dose (for an individual patient) to maintain an international normalized ratio between 2 and 3 was 15.6 mg (range, 6 to 29 mg).

Conclusions— This is the first study of tecarfarin in patients with atrial fibrillation. It appears that tecarfarin may possess advantages over the currently available standard of care, warfarin, by improving time in therapeutic range. Adequately powered prospective trials are warranted to definitively compare tecarfarin with warfarin in clinical settings for which warfarin is indicated.

--------------------------------------------------------------------------------

CLINICAL PERSPECTIVE
[Full Text of Ellis et al.] [Reprint (PDF) Version of Ellis et al.]

--------------------------------------------------------------------------------
Abstract 2 of 12 (Circulation. 2009;120:1036-1040.)
© 2009 American Heart Association, Inc.

--------------------------------------------------------------------------------

Arrhythmia/Electrophysiology

Antiarrhythmics After Ablation of Atrial Fibrillation (5A Study)

Background— Atrial arrhythmias are common early after atrial fibrillation (AF) ablation. We hypothesized that empirical antiarrhythmic drug (AAD) therapy for 6 weeks after AF ablation would reduce the occurrence of atrial arrhythmias.

Methods and Results— We randomized consecutive patients with paroxysmal AF undergoing ablation to empirical antiarrhythmic therapy (AAD group) or no antiarrhythmic therapy (no-AAD group) for the first 6 weeks after ablation. In the no-AAD group, only atrioventricular nodal blocking agents were prescribed. All patients wore a transtelephonic monitor for 4 weeks after discharge and were reevaluated at 6 weeks. The primary end point of the study was a composite of (1) atrial arrhythmias lasting more than 24 hours; (2) atrial arrhythmias associated with severe symptoms requiring hospital admission, cardioversion, or initiation/change of antiarrhythmic drug therapy; and (3) intolerance to antiarrhythmic agent requiring drug cessation. Of 110 enrolled patients (age 55±9 years, 71% male), 53 were randomized to AAD and 57 to no-AAD. There was no difference in baseline characteristics between groups. During the 6 weeks after ablation, fewer patients reached the primary end point in the AAD compared with the no-AAD group (19% versus 42%; P=0.005). There remained fewer events in the AAD group (13% versus 28%; P=0.05) when only end points of AF >24 hours, arrhythmia-related hospitalization, or electrical cardioversion were compared.

Conclusions— AAD treatment during the first 6 weeks after AF ablation is well tolerated and reduces the incidence of clinically significant atrial arrhythmias and need for cardioversion/hospitalization for arrhythmia management.

--------------------------------------------------------------------------------

CLINICAL PERSPECTIVE
--------------------------------------------------------------------------------
Abstract 3 of 12 (Circulation. 2009;120:1041-1047.)
© 2009 American Heart Association, Inc.

--------------------------------------------------------------------------------

Epidemiology and Prevention

Metabolic Syndrome, Inflammation, and Risk of Symptomatic Peripheral Artery Disease in Women
A Prospective Study

Background— The metabolic syndrome (MetS) is associated with incident myocardial infarction and stroke and is linked with subclinical inflammation; however, prospective data pertaining to MetS and future peripheral artery disease (PAD) are sparse, with few studies examining the role of inflammation. We therefore evaluated the relationship between MetS, inflammation, and incident PAD.

Methods and Results— We conducted a prospective cohort study among 27 111 women free of baseline cardiovascular disease who were participating in the Women’s Health Study. Subjects were followed for incident symptomatic PAD (n=114; median cohort follow-up 13.3 years). We used Cox proportional hazards models to compare PAD risk among women with and without MetS. We also evaluated relationships between MetS and subclinical inflammation as measured by high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-1 and adjusted for these biomarkers in multivariable models. Women with MetS had a 62% increased risk of future PAD (hazard ratio 1.62, 95% confidence interval 1.10 to 2.38). After multivariable adjustment, MetS remained significantly associated with PAD (adjusted hazard ratio 1.48, 95% confidence interval 1.01 to 2.18), with a 21% risk increase per additional MetS-defining trait (adjusted hazard ratio 1.21, 95% confidence interval 1.06 to 1.39). In women with and without MetS, respectively, median levels of high-sensitivity C-reactive protein were 4.0 versus 1.5 mg/L (P<0.0001), and median levels of soluble intercellular adhesion molecule-1 were 374 versus 333 ng/mL (P<0.0001). When high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-1 were added to multivariable models, risk associated with MetS was substantially attenuated and no longer significant (hazard ratio 1.14, 95% confidence interval 0.75 to 1.73).

Conclusions— MetS is associated with an increased risk of future symptomatic PAD in women. This risk appears to be mediated largely by the effects of inflammation and endothelial activation.

--------------------------------------------------------------------------------

CLINICAL PERSPECTIVE

--------------------------------------------------------------------------------
Abstract 4 of 12 (Circulation. 2009;120:1048-1055.)
© 2009 American Heart Association, Inc.

--------------------------------------------------------------------------------

Epidemiology and Prevention

Pathophysiological Changes in Calf Muscle Predict Mobility Loss at 2-Year Follow-Up in Men and Women With Peripheral Arterial Disease

Background— Associations of pathophysiological calf muscle characteristics with functional decline in people with lower extremity peripheral arterial disease are unknown.

Methods and Results— Three hundred seventy participants with peripheral arterial disease underwent baseline measurement of calf muscle area, density, and percent fat with the use of computed tomography. Participants were followed up annually for 2 years. The outcome of mobility loss was defined as becoming unable to walk 1/4 mile or walk up and down 1 flight of stairs without assistance among those without baseline mobility limitations. Additional outcomes were 20% decline in 6-minute walk distance and becoming unable to walk for 6 minutes continuously among participants who walked continuously for 6 minutes at baseline. With adjustment for age, sex, race, body mass index, the ankle-brachial index, smoking, physical activity, relevant medications, and comorbidities, lower calf muscle density (P for trend <0.001) and lower calf muscle area (P for trend=0.039) were each associated with increased mobility loss rates. Compared with participants in the highest baseline tertiles, participants in the lowest tertile of calf muscle percent fat had a hazard ratio of 0.18 for incident mobility loss (95% confidence interval, 0.06 to 0.55; P=0.003), and participants in the lowest tertile of muscle density had a 3.50 hazard ratio for incident mobility loss (95% confidence interval, 1.28 to 9.57; P=0.015). No significant associations of calf muscle characteristics with 6-minute walk outcomes were observed.

Conclusions— Our findings suggest that interventions to prevent mobility loss in peripheral arterial disease should focus on reversing pathophysiological findings in calf muscle.

--------------------------------------------------------------------------------

CLINICAL PERSPECTIVE

--------------------------------------------------------------------------------
Abstract 5 of 12 (Circulation. 2009;120:1056-1064.)
© 2009 American Heart Association, Inc.

--------------------------------------------------------------------------------

Epidemiology and Prevention

A Prospective Study of Bone Lead Concentration and Death From All Causes, Cardiovascular Diseases, and Cancer in the Department of Veterans Affairs Normative Aging Study

Background— Blood lead concentration has been associated with mortality from different causes in several studies. Many effects of lead exposure that might increase risk of death are likely to result from cumulative exposure, for which bone lead is a better biomarker than blood lead. The association between bone lead levels and mortality has not been explored.

Methods and Results— We prospectively assessed the association between both blood lead and bone lead, analyzed with the use of K-shell x-ray fluorescence, and mortality among 868 men in the Normative Aging Study. We identified 241 deaths over an average of 8.9 (SD=3.9) years of follow-up. We calculated adjusted hazard ratios and 95% confidence intervals using Cox proportional hazards. Compared with the lowest tertile of patella bone lead, the fully adjusted hazard ratios in the highest tertile for all-cause and cardiovascular mortality (n=137 deaths) were 2.52 (95% confidence interval, 1.17 to 5.41) and 5.63 (95% confidence interval, 1.73 to 18.3), respectively. The age-, smoking-, and race-adjusted hazard ratio for ischemic heart disease mortality (n=62 deaths) in the highest tertile was 8.37 (95% confidence interval, 1.29 to 54.4). Results were similar for tibia lead. Bone lead was not associated with cancer, and blood lead was not associated with any mortality category.

Conclusions— We found bone lead to be associated with all-cause and cardiovascular mortality in an environmentally exposed population with low blood lead levels. This study suggests that cumulative lead exposure from prior decades of high environmental exposures continues to significantly affect risk of death despite recent declines in environmental lead exposure.

--------------------------------------------------------------------------------

CLINICAL PERSPECTIVE
--------------------------------------------------------------------------------
Abstract 6 of 12 (Circulation. 2009;120:1065-1074.)
© 2009 American Heart Association, Inc.

--------------------------------------------------------------------------------

Heart Failure

Cardiomyocyte-Specific Overexpression of Human Stem Cell Factor Improves Cardiac Function and Survival After Myocardial Infarction in Mice
Background— Soluble stem cell factor (SCF) has been shown to mobilize bone marrow stem cells and improve cardiac repair after myocardial infarction (MI). However, the effect of membrane-associated SCF on cardiac remodeling after MI is not known. The present study investigated the effects of cardiomyocyte-specific overexpression of the membrane-associated isoform of human SCF (hSCF) on cardiac function after MI.

Methods and Results— A novel mouse model with tetracycline-inducible and cardiac-specific overexpression of membrane-associated hSCF was generated. MI was induced by left coronary artery ligation. Thirty-day mortality after MI was decreased in hSCF/tetracycline transactivator (tTA) compared with wild-type mice. In vivo cardiac function was significantly improved in hSCF/tTA mice at 5 and 30 days after MI compared with wild-type mice. Endothelial progenitor cell recruitment and capillary density were increased and myocardial apoptosis was decreased in the peri-infarct area of hSCF/tTA mice. Myocyte size was decreased in hSCF/tTA mice 30 days after MI compared with WT mice. Furthermore, hSCF overexpression promoted de novo angiogenesis as assessed by matrigel implantation into the left ventricular myocardium.

Conclusions— Cardiomyocyte-specific overexpression of hSCF improves myocardial function and survival after MI. These beneficial effects of hSCF may result from increases in endothelial progenitor cell recruitment and neovascularization and decreases in myocardial apoptosis and cardiac remodeling.

--------------------------------------------------------------------------------

CLINICAL PERSPECTIVE
--------------------------------------------------------------------------------
Abstract 7 of 12 (Circulation. 2009;120:1075-1083.)
© 2009 American Heart Association, Inc.

--------------------------------------------------------------------------------

Heart Failure

Engraftment, Differentiation, and Functional Benefits of Autologous Cardiosphere-Derived Cells in Porcine Ischemic Cardiomyopathy

Background— Cardiosphere-derived cells (CDCs) isolated from human endomyocardial biopsies reduce infarct size and improve cardiac function in mice. Safety and efficacy testing in large animals is necessary for clinical translation.

Methods and Results— Mesenchymal stem cells, which resemble CDCs in size and thrombogenicity, have been associated with infarction after intracoronary infusion. To maximize CDC engraftment while avoiding infarction, we optimized the infusion protocol in 19 healthy pigs. A modified cocktail of CDCs in calcium-free PBS, 100 U/mL of heparin, and 250 µg/mL of nitroglycerin eliminated infusion-related infarction. Subsequent infusion experiments in 17 pigs with postinfarct left ventricular dysfunction showed CDC doses 107 but <2.5x107 result in new myocardial tissue formation without infarction. In a pivotal randomized study, 7 infarcted pigs received 300 000 CDCs/kg (107 total) and 7 received placebo (vehicle alone). Cardiac magnetic resonance imaging 8 weeks later showed CDC treatment decreased relative infarct size (19.2% to 14.2% of left ventricle infarcted, P=0.01), whereas placebo did not (17.7% to 15.3%, P=0.22). End-diastolic volume increased in placebo, but not in CDC-treated animals. Hemodynamically, the rate of pressure change (dP/dt) maximum and dP/dt minimum were significantly better with CDC infusion. There was no difference between groups in the ability to induce ventricular tachycardia, nor was there any tumor or ectopic tissue formation.

Conclusions— Intracoronary delivery of CDCs in a preclinical model of postinfarct left ventricular dysfunction results in formation of new cardiac tissue, reduces relative infarct size, attenuates adverse remodeling, and improves hemodynamics. The evidence of efficacy without obvious safety concerns at 8 weeks of follow-up motivates human studies in patients after myocardial infarction and in chronic ischemic cardiomyopathy.

--------------------------------------------------------------------------------

CLINICAL PERSPECTIVE

--------------------------------------------------------------------------------
Abstract 8 of 12 (Circulation. 2009;120:1084-1090.)
© 2009 American Heart Association, Inc.

--------------------------------------------------------------------------------

Hypertension

Baseline Values but Not Treatment-Induced Changes in Carotid Intima-Media Thickness Predict Incident Cardiovascular Events in Treated Hypertensive Patients
Findings in the European Lacidipine Study on Atherosclerosis (ELSA)

Background— Baseline carotid intima-media thickness (IMT) and plaques are considered predictors of cardiovascular events, but whether they maintain predictive value in treated hypertensive patients and whether time-related (or treatment-induced) IMT changes are additional predictors are unknown.

Methods and Results— Analyses were performed of the data from the European Lacidipine Study on Atherosclerosis (ELSA), a large, randomized, intervention trial in which 2334 hypertensive patients from 7 European countries were followed up under effective antihypertensive treatment for 3.75 years. Kaplan–Meier curves indicated progressively lower survival free of any type of outcome except stroke, with increasing baseline IMT quartiles or increasing IMT values, even after adjustment for major baseline risk factors. Incidence of any outcome except stroke also was related to baseline number of carotid plaques. However, when both baseline and on-treatment IMT values were entered in Cox proportional-hazards models, differences in IMT compared with baseline did not predict cardiovascular outcomes. Although on-treatment rather than baseline IMT values significantly entered some of the proportional-hazards models, baseline and on-treatment IMTs were highly correlated, and therefore these results are inconclusive.

Conclusions— ELSA shows that carotid intima-media thickening and plaques are important added risks of cardiovascular outcomes in a treated hypertensive population independently of blood pressure and traditional risk factors. However, the analysis failed to show a predictive role of treatment-dependent IMT changes. These negative conclusions should be tempered by the limitations inherent in the smallness of these changes compared with the large individual differences in baseline IMTs.

--------------------------------------------------------------------------------

CLINICAL PERSPECTIVE

--------------------------------------------------------------------------------
Abstract 9 of 12 (Circulation. 2009;120:1091-1098.)
© 2009 American Heart Association, Inc.

--------------------------------------------------------------------------------

Imaging

Real-Time 3-Dimensional Echocardiography Provides New Insight Into Mechanisms of Tricuspid Valve Regurgitation in Patients With Hypoplastic Left Heart Syndrome

Background— Tricuspid regurgitation in hypoplastic left heart syndrome has an impact on outcome, but its mechanisms remain unclear.

Methods and Results— Real-time 3-dimensional echocardiography was performed in 35 patients with hypoplastic left heart syndrome (age, 1 month to 10 years; 10 after first-stage Norwood, 12 after superior cavopulmonary shunt, 13 after Fontan). From the 3-dimensional data set, we marked the annulus in systole and diastole. At mid systole, we marked the location of the papillary muscle tip and point of chordal attachment to the leaflet. We traced the surfaces of the tricuspid valve leaflets and measured the volume of leaflet prolapse, tethering, annular and septal leaflet areas, and papillary muscle position. Seventeen patients had moderate tricuspid regurgitation (prolapse, 7; tethered leaflets, 7) and 18 mild (prolapse, 0; tethered leaflets, 7). Multiple linear regression analysis revealed that moderate tricuspid regurgitation is associated with leaflet tethering and prolapse; that in hypoplastic left heart syndrome with tethered leaflets, the papillary muscle is displaced laterally and the tricuspid annulus is more planar; and that enlargement of the annulus at mid systole, small septal leaflet area, and age affect the degree of prolapse.

Conclusion— In hypoplastic left heart syndrome, moderate tricuspid regurgitation may be associated with increasing age, geometrical changes of the annulus, leaflet prolapse, lateral papillary muscle displacement, and subsequent leaflet tethering, as well as a smaller septal leaflet.

--------------------------------------------------------------------------------

CLINICAL PERSPECTIVE

--------------------------------------------------------------------------------
Abstract 10 of 12 (Circulation. 2009;120:1099-1107.)
© 2009 American Heart Association, Inc.

--------------------------------------------------------------------------------

Transplantation

Novel Small Interfering RNA–Containing Solution Protecting Donor Organs in Heart Transplantation

Background— Ischemia/reperfusion injury is a major factor in graft quality and subsequent function in the transplantation setting. We hypothesize that the process of RNA interference may be used to "engineer" a graft to suppress expression of genes associated with inflammation, apoptosis, and complement, which are believed to cause ischemia/reperfusion injury. Such manipulation of pathological gene expression may be performed by treatment of the graft ex vivo with small interfering RNA (siRNA) as part of the preservation procedure.

Methods and Results— Heart grafts from BALB/c mice were preserved in UW solution (control) or UW solution containing siRNAs targeting tumor necrosis factor-, C3, and Fas genes (siRNA solution) at 4°C for 48 hours and subsequently transplanted into syngeneic recipients. Tumor necrosis factor-, C3, and Fas genes were elevated by ischemia/reperfusion injury after 48 hours of preservation in UW solution. Preservation in siRNA solution knocked down gene expression at the level of messenger RNA and protein in the grafts after transplantation. All grafts preserved in siRNA solution showed strong contraction, whereas grafts preserved in control solution demonstrated no detectable contraction by high-frequency ultrasound scanning. siRNA solution–treated organs exhibited improved histology and diminished neutrophil and lymphocyte infiltration compared with control solution–treated organs. Furthermore, the treated heart grafts retained strong beating up to the end of the observation period (>100 days), whereas all control grafts lost function within 8 days.

Conclusion— Incorporation of siRNA into organ storage solution is a feasible and effective method of attenuating ischemia/reperfusion injury, protecting cardiac function, and prolonging graft survival.

--------------------------------------------------------------------------------

CLINICAL PERSPECTIVE

--------------------------------------------------------------------------------
Abstract 11 of 12 (Circulation. 2009;120:1108-1114.)
© 2009 American Heart Association, Inc.

--------------------------------------------------------------------------------

Valvular Heart Disease

Accelerated Infusion of Streptokinase for the Treatment of Left-Sided Prosthetic Valve Thrombosis
A Randomized Controlled Trial

Background— No large prospective studies have evaluated the efficacy of fibrinolytic therapy for left-sided prosthetic valve thrombosis, yet it remains the first line of treatment in developing countries.

Methods and Results— We performed a randomized controlled trial comparing an accelerated infusion with the conventional infusion of streptokinase in 120 patients with a first episode of left-sided prosthetic valve thrombosis. The primary outcome measure was the occurrence of a complete clinical response, defined as objectively documented complete restoration of valve function in the absence of major complications. The secondary outcome was a composite of death, major bleeding, embolic stroke, or non–central nervous system systemic embolism. Patients were recruited over a 2.5-year period at a single center in India. Complete clinical response occurred in 38 (64.4%) of 59 patients with the accelerated infusion compared with 32 (53.3%) of 60 with the conventional infusion (hazard ratio 1.6, 95% confidence interval 0.9 to 2.5, P=0.055). There was no significant difference in the occurrence of the composite secondary outcome (hazard ratio 1.4, 95% confidence interval 0.5 to 3.5, P=0.50) or major bleeding (hazard ratio 2.2, 95% confidence interval 0.6 to 7.7, P=0.24) with the accelerated infusion. The success rate with fibrinolytic therapy was low overall (59%) and very low in patients in New York Heart Association functional class III/IV (24%).

Conclusions— The large number of patients recruited from a single center underscores the massive burden of prosthetic valve thrombosis in developing countries. Fibrinolytic therapy with streptokinase is less efficacious than previously believed. The accelerated streptokinase infusion is not better than the standard infusion for left-sided prosthetic valve thrombosis. Developing countries urgently need more effective strategies to prevent and treat prosthetic valve thrombosis.

--------------------------------------------------------------------------------

CLINICAL PERSPECTIVE

--------------------------------------------------------------------------------
Abstract 12 of 12 (Circulation. 2009;120:1115-1122.)
© 2009 American Heart Association, Inc.

--------------------------------------------------------------------------------

Vascular Medicine

Improved Oral Anticoagulation After a Dietary Vitamin K–Guided Strategy
A Randomized Controlled Trial

Background— Dietary vitamin K is thought to be an important factor that interferes with anticoagulation stability, but the clinical applicability of this interaction has not been evaluated adequately in prospective studies.

Methods and Results— In a randomized controlled trial that enrolled outpatients with a recent international normalized ratio (INR) outside the therapeutic target, we compared 2 strategies to optimize long-term oral anticoagulation: (1) a conventional approach based on changes in anticoagulant prescription and (2) a dietary vitamin K–guided strategy based on simple modifications of the amount of vitamin K–rich foods ingested per week. The primary efficacy end point was the percentage of patients who achieved a prespecified INR target at 90 days after randomization. Study population (n=132) predominantly included men with mechanical heart prostheses (58%) or atrial fibrillation (35%). Over time, patients allocated to the vitamin K–guided strategy reached the prespecified INR more frequently so that after 90 days of follow-up, 74% were on target compared with 58% of patients managed conventionally (P=0.04). Patients allocated to the dietary vitamin K–guided strategy had the same magnitude and direction of INR variation as those observed with the conventional approach in the short term (15 days) for both underanticaogulated and overanticoagulated patients. Minor bleeding or use of parenteral vitamin K were also marginally less frequent in patients managed according to the dietary intervention (1 [1.5%] versus 7 [11%]; P=0.06).

Conclusions— A vitamin K–guided management strategy to adjust long-term oral anticoagulation is feasible and safe and may result in an increased chance of reaching target levels of INR.

邀请讨论

搜索

2009-09-22 08:37 浏览 : 2869 回复 : 22

投票
收藏 4
打赏
引用
分享
- 微信扫一扫
- 新浪微博
- 丁香客
- 复制网址
举报
- 广告宣传推广
- 政治敏感、违法虚假信息
- 恶意灌水、重复发帖
- 违规侵权、站友争执
- 附件异常、链接失效
- 其他

Bedlamite 编辑于 2009-09-22 08:44

• 患者家属撕心裂肺的一跪让我深思许久，记录一下规培生涯里遇到的一些人、一些事

paul321

重症医学科

铁杆站友

2楼

认领第10篇

2009-09-22 10:59

投票
收藏
打赏
引用
分享
- 微信扫一扫
- 新浪微博
- 丁香客
- 复制网址
举报
- 广告宣传推广
- 政治敏感、违法虚假信息
- 恶意灌水、重复发帖
- 违规侵权、站友争执
- 附件异常、链接失效
- 其他

paul321 编辑于 2009-09-22 11:09

• 浙一咋了？？爆炸了？？？

鹏程

丁香园准中级站友

3楼

认领第12篇

2009-09-22 12:10

投票
收藏
打赏
引用
分享
- 微信扫一扫
- 新浪微博
- 丁香客
- 复制网址
举报
- 广告宣传推广
- 政治敏感、违法虚假信息
- 恶意灌水、重复发帖
- 违规侵权、站友争执
- 附件异常、链接失效
- 其他

• 教育部：今年国家定向培养免费医学生，你会报考吗？——回帖

paul321

重症医学科

铁杆站友

+1 积分
4楼

第10篇移植
Novel Small Interfering RNA–Containing Solution Protecting Donor Organs in Heart Transplantation
心脏移植中含有小分子干扰RNA的新型溶液对供体器官具有保护作用

Background— Ischemia/reperfusion injury is a major factor in graft quality and subsequent function in the transplantation setting. We hypothesize that the process of RNA interference may be used to "engineer" a graft to suppress expression of genes associated with inflammation, apoptosis and complement, which are believed to cause ischemia/reperfusion injury. Such manipulation of pathological gene expression may be performed by treatment of the graft ex vivo with small interfering RNA (siRNA) as part of the preservation procedure.
背景—在移植过程中缺血/再灌注损伤是影响供体器官质量及其后功能的主要因素。炎症，凋亡和补体激活是引起缺血/再灌注损伤的主要原因，我们假设RNA干扰技术可以设定供体器官内的程序从而抑制相关基因的表达。在保存阶段应用小分子干扰RNA(siRNA)对供体器官进行体外处理可以达到调控病理状态下基因表达的目的。

Methods and Results— Heart grafts from BALB/c mice were preserved in UW solution (control) or UW solution containing siRNAs targeting tumor necrosis factor-α, C3, and Fas genes (siRNA solution) at 4°C for 48 hours and subsequently transplanted into syngeneic recipients. Tumor necrosis factor-α, C3 and Fas genes were elevated by ischemia/reperfusion injury after 48 hours of preservation in UW solution. Preservation in siRNA solution knocked down gene expression at the level of messenger RNA and protein in the grafts after transplantation. All grafts preserved in siRNA solution showed strong contraction, whereas grafts preserved in control solution demonstrated no detectable contraction by high-frequency ultrasound scanning. siRNA solution–treated organs exhibited improved histology and diminished neutrophil and lymphocyte infiltration compared with control solution–treated organs. Furthermore, the treated heart grafts retained strong beating up to the end of the observation period (>100 days), whereas all control grafts lost function within 8 days.
方法和结果—我们将取自BALB/c小鼠的心脏分别保存在UW溶液（对照组）或含有针对肿瘤坏死因子-α，补体C3和Fas 基因的siRNA的UW溶液中（siRNA处理组），保存条件为4°C，保存时间为48小时，随后将心脏移植入同源小鼠体内。移植后48小时缺血/再灌注损伤引起对照组心脏内肿瘤坏死因子-α，补体C3和Fas 基因表达显著上调。siRNA在信使RNA和蛋白水平使上述基因发生了基因沉默。高频超声扫描显示所有siRNA处理组心脏表现出良好的心肌收缩性，而对照组心脏没有明显的收缩。与对照组心脏相比，siRNA处理组心脏的组织学变化改善，中性粒细胞和淋巴细胞浸润减少。更加重要的是，处理组心脏在观察末期(>100天)仍然保持强有力的搏动，而对照组心脏在8天内丧失了功能。

Conclusion— Incorporation of siRNA into organ storage solution is a feasible and effective method of attenuating ischemia/reperfusion injury, protecting cardiac function and prolonging graft survival.
结论—在供体心脏保存溶液中加入siRNA是一种可行的、有效的减轻缺血/再灌注损伤，保护心脏功能并延长心脏存活时间的方法。

2009-09-22 12:48

投票
收藏
打赏
引用
分享
- 微信扫一扫
- 新浪微博
- 丁香客
- 复制网址
举报
- 广告宣传推广
- 政治敏感、违法虚假信息
- 恶意灌水、重复发帖
- 违规侵权、站友争执
- 附件异常、链接失效
- 其他

paul321 编辑于 2009-09-22 12:57

• 【讨论】游离腕横纹皮瓣

心血管

Circulation 2009年9月22日

提示

丁香园旗下网站

关于丁香园

官方链接

心血管

分享到：

微信扫一扫

Circulation 2009年9月22日

微信扫一扫

微信扫一扫

微信扫一扫

微信扫一扫

提示

丁香园旗下网站

关于丁香园

官方链接