Abstract:
BACKGROUND:Thrombolytic therapy of acute myocardial infarction (AMI) is evolving toward bolus administration. Derivatization of proteins with polyethylene glycol (PEG) may reduce their clearance. METHODS AND RESULTS:A staphylokinase (SakSTAR) variant with 12 amino acid substitutions to reduce its antigenicity, SakSTAR (K35A, E65Q, K74R, E80A, D82A, T90A, E99D, T101S, E108A, K109A, K130T, K135R), and with Ser in position 3 mutated into Cys (code SY161), was derivatized with maleimide-PEG with M:(r) of 5,000 (P5), 10,000 (P10), or 20,000 (P20). The PEGylated variants recognized only one third of the antibodies elicited with wild-type SakSTAR in AMI patients. In experimental animals, plasma clearances were reduced 2. 5- to 5-fold with P5, 5- to 20-fold with P10, and 20-fold with P20, and bolus injection induced pulmonary plasma clot lysis at doses inversely related to their clearance. Intravenous bolus injection of 5 mg of the P5, P10, or P20 variants in AMI patients was associated with plasma half-lives (t(1/2alpha)) of 13, 30, and 120 minutes and clearances of 75, 43, and 8 mL/min, respectively, compared with 3 minutes and 360 mL/min for SakSTAR. Injection of 5 mg P5 variant restored TIMI-3 flow within 60 minutes in 14 of 18 AMI patients (78%, 95% CI 55% to 91%) and of 2.5 mg in 7 of 11 patients (63%, 95% CI 35% to 85%), both in the absence of fibrinogen degradation. The immunogenicity of the variants was significantly (P:<0.002) reduced. CONCLUSIONS:The staphylokinase variant SY161-P5, derivatized with one linear polyethylene glycol molecule of M:(r) 5000, is a promising fibrin-selective agent for single-bolus coronary thrombolysis.
journal_name
Circulationjournal_title
Circulationauthors
Collen D,Sinnaeve P,Demarsin E,Moreau H,De Maeyer M,Jespers L,Laroche Y,Van de Werf Fdoi
10.1161/01.cir.102.15.1766subject
Has Abstractpub_date
2000-10-10 00:00:00pages
1766-72issue
15eissn
0009-7322issn
1524-4539journal_volume
102pub_type
临床试验,杂志文章相关文献
CIRCULATION文献大全abstract:BACKGROUND:As part of the Worcester Heart Attack Study, a community-wide study examining changes over time in the incidence and long-term case-fatality rates of greater Worcester, Mass, residents hospitalized with confirmed acute myocardial infarction (AMI), we investigated the hypothesis that census tract-level socioe...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.104.496174
更新日期:2005-06-14 00:00:00
abstract:BACKGROUND:Atrial fibrillation is the most common cardiac arrhythmia. Ventricular proarrhythmia hinders pharmacological atrial fibrillation treatment. Modulation of atrium-specific Kir3.x channels, which generate a constitutively active current (I(K,ACh-c)) after atrial remodeling, might circumvent this problem. Howeve...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.113.005019
更新日期:2013-12-24 00:00:00
abstract:BACKGROUND:Mechanical dyssynchrony is a potential means to predict response to cardiac resynchronization therapy (CRT). We hypothesized that novel echocardiographic image speckle tracking can quantify dyssynchrony and predict response to CRT. METHODS AND RESULTS:Seventy-four subjects were studied: 64 heart failure pat...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.105.571455
更新日期:2006-02-21 00:00:00
abstract:BACKGROUND:Biventricular direct cardiac compression (DCC) can potentially support the failing heart without the complications associated with a blood/device interface. The effect of uniform DCC on left and right ventricular performance was evaluated in 7 isolated canine heart preparations. METHODS AND RESULTS:A comput...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.99.16.2177
更新日期:1999-04-27 00:00:00
abstract::This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations for advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recen...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIR.0000000000000893
更新日期:2020-10-20 00:00:00
abstract::The directions and magnitudes of time-normalized P, QRS, and ST vectors, and other ECG parameters were analyzed during and after multistage exercise in 56 ostensibly healthy men aged 23 to 62. By selective averaging with a digital computer system a single representative beat was obtained from each stage. Measurements ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.52.4.570
更新日期:1975-10-01 00:00:00
abstract:BACKGROUND:Endothelial dysfunction may contribute to the risk of premature atherosclerosis in patients with diabetes. Endothelin (ET-1) may be involved in this process by activating smooth muscle cell mitogenesis and leukocyte adhesion. We sought to assess the activity of endogenous ET-1 in a group of patients with typ...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/01.cir.0000032260.01569.64
更新日期:2002-10-01 00:00:00
abstract:BACKGROUND:At physiological concentrations, 17beta-estradiol selectively enhances endothelium-dependent coronary vasodilation by an unknown mechanism in postmenopausal women. METHODS AND RESULTS:To assess the contribution of nitric oxide (NO) to the vascular effects of estradiol, we measured coronary epicardial and mi...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.96.9.2795
更新日期:1997-11-04 00:00:00
abstract:BACKGROUND:Several noninvasive methods are available to investigate the severity of extracoronary atherosclerotic disease. No population-based study has yet examined whether differences exist between these measures with regard to their predictive value for myocardial infarction (MI) or whether a given measure of athero...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000120708.59903.1B
更新日期:2004-03-09 00:00:00
abstract:BACKGROUND:The purposes of this study were to evaluate the comparative accuracy of dobutamine echocardiography and quantitative rest-redistribution 201Tl tomography in the prediction of recovery of function after revascularization and to assess the relation of contractile reserve to thallium uptake. METHODS AND RESULT...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.95.3.626
更新日期:1997-02-04 00:00:00
abstract::In a placebo-controlled, randomized, cross-over, double-blind study of 12 patients with stable exertional angina, we measured at rest and during bicycle exercise the effects of 20 mg of nifedipine administered sublingually on hemodynamics and systemic and regional oxygen extraction and metabolism. Nifedipine decreased...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.71.4.787
更新日期:1985-04-01 00:00:00
abstract:BACKGROUND:An objective of the United States' Healthy People 2010 Initiative is to eliminate disparities based on socioeconomic status. We assessed the effect of difficulty affording health care on the health status (symptoms, function, and quality of life) of patients treated with percutaneous coronary intervention or...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.104.474775
更新日期:2005-05-24 00:00:00
abstract:BACKGROUND:Angiogenesis is a critical feature of plaque development in atherosclerosis and might play a key role in both the initiation and later rupture of plaques that lead to myocardial infarction and stroke. The precursory molecular or cellular events that initiate plaque growth and that ultimately contribute to pl...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000093185.16083.95
更新日期:2003-11-04 00:00:00
abstract:BACKGROUND:The Doppler wire-derived (relative) coronary flow velocity reserve (CVR) that is used to evaluate functional significance of a coronary stenosis is a method performed only by interventional cardiologists. An angiographic method would be useful in the diagnostic catheterization laboratory. For this purpose, w...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/01.CIR.0000074279.44131.DE
更新日期:2003-06-24 00:00:00
abstract:BACKGROUND:Left ventricular wall motion (WM) abnormalities have recognized prognostic significance in patients with coronary or other heart diseases; however, whether abnormal WM predicts adverse events in adults without overt cardiovascular disease has not been assessed. Our objective was to determine whether echocard...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.106.652149
更新日期:2007-07-10 00:00:00
abstract:BACKGROUND:Carotid artery stenting (CAS) has recently emerged as a potential alternative to carotid endarterectomy. Cerebral embolization is the most devastating complication of CAS, and the echogenicity of carotid plaque has been indicated as one of the risk factors involved. This is the first study to analyze the rol...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000138103.91187.E3
更新日期:2004-08-10 00:00:00
abstract:BACKGROUND:A number of parameters reflecting the effects of idiopathic dilated cardiomyopathy (IDC) on the structure and function of myosin from the human myocardium were analyzed. METHODS AND RESULTS:The content of the regulatory light chain, LC2, was reduced in myopathic heart myosin in contrast to the controls in w...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.85.5.1720
更新日期:1992-05-01 00:00:00
abstract:BACKGROUND:Considerable controversy exists on the association between coffee consumption and cardiovascular disease (CVD) risk. A meta-analysis was performed to assess the dose-response relationship of long-term coffee consumption with CVD risk. METHODS AND RESULTS:PubMed and EMBASE were searched for prospective cohor...
journal_title:Circulation
pub_type: 杂志文章,meta分析,评审
doi:10.1161/CIRCULATIONAHA.113.005925
更新日期:2014-02-11 00:00:00
abstract:BACKGROUND:The CAPRICORN trial has shown that carvedilol improved outcome in patients with left ventricular dysfunction after acute myocardial infarction treated with ACE inhibitors. The aim of this substudy was to determine the effects of carvedilol on left ventricular remodeling in this patient group. METHODS AND RE...
journal_title:Circulation
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1161/01.CIR.0000108928.25690.94
更新日期:2004-01-20 00:00:00
abstract:BACKGROUND:Previous studies have reported an association between chronic Helicobacter pylori infection and ischemic heart disease. However, it is not clear whether this association is really due to the virulence of the bacterium or is merely the result of confounding factors (in particular, age and social class). METH...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.97.17.1675
更新日期:1998-05-05 00:00:00
abstract:BACKGROUND:Long-term rapid atrial pacing may result in atrial fibrillation (AF) in dogs. Whether there is histological evidence for neural remodeling is unclear. METHOD AND RESULTS:We performed rapid right atrial pacing in 6 dogs for 111+/-76 days to induce sustained AF. Tissues from 6 healthy dogs were used as contro...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.103.1.22
更新日期:2001-01-02 00:00:00
abstract:BACKGROUND:Atherosclerosis is a multifactorial disease in which inflammatory processes play an important role. Inflammation underlies lesion evolution at all stages, from establishment to plaque rupture and thrombosis. Costimulatory molecules of the tumor necrosis factor superfamily such as CD40/CD40L and OX40/OX40L ha...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.107.699173
更新日期:2008-03-11 00:00:00
abstract:BACKGROUND:Hypercholesterolemia and sickle cell disease (SCD) impair endothelium-dependent vasodilation by dissimilar mechanisms. Hypercholesterolemia impairs vasodilation by a low-density lipoprotein (LDL)-dependent mechanism. SCD has been characterized as a chronic state of inflammation in which xanthine oxidase (XO)...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000070589.61860.A9
更新日期:2003-05-13 00:00:00
abstract:BACKGROUND:Several clinical studies have demonstrated a general superiority of biphasic waveform defibrillation compared with monophasic waveform defibrillation using epicardial lead systems. To test the breadth of utility of biphasic waveforms in humans, a prospective, randomized evaluation of defibrillation efficacy ...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.84.2.665
更新日期:1991-08-01 00:00:00
abstract:BACKGROUND:The Ross operation is an alternative to mechanical aortic valve replacement in the young. Early dilatation of the pulmonary autograft root exposed to the systemic circulation has been reported. To define the prevalence of, risk factors for, and consequences of late autograft dilatation, outcome in all consec...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.0000089183.92233.75
更新日期:2003-09-09 00:00:00
abstract:BACKGROUND:Contrast agents can cause a reduction in renal function that may be due to the generation of reactive oxygen species. Conflicting evidence suggests that administration of the antioxidant acetylcysteine prevents this renal impairment. The action of other antioxidant agents has not been investigated. METHODS ...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.CIR.0000146396.19081.73
更新日期:2004-11-02 00:00:00
abstract:BACKGROUND:The renin-angiotensin system regulates blood pressure through its effects on vascular tone, renal hemodynamics, and renal sodium and fluid balance. METHODS AND RESULTS:Using data from a large population-based sample of 1488 siblings having a mean age of 14.8 years and belonging to the youngest generation of...
journal_title:Circulation
pub_type: 评论,杂志文章
doi:10.1161/01.cir.97.18.1773
更新日期:1998-05-12 00:00:00
abstract:BACKGROUND:Keratinocyte growth factor (KGF) has been shown to play an important role in pneumocyte proliferation and lung development. We hypothesized that exogenous KGF would enhance postpneumonectomy compensatory lung growth through alveolar proliferation. METHODS AND RESULTS:Adult Sprague-Dawley rats were used. Lef...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:2002-09-24 00:00:00
abstract:BACKGROUND:The site of cannulation for repair of ascending aortic dissection remains controversial. We present our experience with ascending aortic cannulation for acute aortic dissection type A. METHODS AND RESULTS:From January 1988 to September 2007, we operated on 242 patients for acute aortic dissection type A. Me...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.108.844480
更新日期:2009-09-15 00:00:00
abstract:BACKGROUND:Numerous scales exist for the classification of major bleeding events. Limited data compare the most commonly used bleeding scales within a single at-risk cohort of patients with atrial fibrillation. Here, we analyze bleeding outcomes according to the ISTH (International Society on Thrombosis and Hemostasis)...
journal_title:Circulation
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1161/CIRCULATIONAHA.119.041346
更新日期:2019-11-26 00:00:00