ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundThe antiarrhythmic drugs quinidine and verapamil are known to block alpha1-adrenoceptors(alpha1ARs). alpha1ARs are a heterogeneous family of three subtypes (alpha1A, alpha1B, and alpha1D), and little is known about the effects of quinidine and verapamil on the different human alpha1AR subtypes.Methods and Results-Reverse transcriptase-polymerase chain reaction showed that all alpha1AR subtypes are expressed in both human heart (atrium and ventricle) and the mesenteric artery. Pharmacological profiles of quinidine and verapamil actions on the alpha1AR subtypes were characterized with Chinese hamster ovary cells stably expressing cloned human alpha1AR subtypes. Radioligand binding studies showed that quinidine and verapamil had high affinities for all alpha1AR subtypes. Also, both drugs synergistically inhibited alpha (1) AR-mediated inositol 1,4,5-triphosphate production at the clinical effective concentration range (1 [micro sign]mol/L quinidine and 0.1 [micro sign]mol/L verapamil).ConclusionsThe results show that all alpha1AR subtypes are expressed in the human cardiovascular system and that quinidine and verapamil may have a potent, synergistic inhibitory effect on the alpha1ARs. Clinically observed hypotension after quinidine plus verapamil can be explained by their synergistic inhibitory effects on human alpha1ARs. (Circulation. 1998;97:1227-1230.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundStudies of selected populations suggest that anticoagulation in atrial fibrillation is underused and that nonclinical factors influence the use of this stroke-preventing therapy. We wished to examine recent national trends and predictors of warfarin sodium use in atrial fibrillation.Methods and Results-A nationally representative sample of office visits from the 1989 to 1996 National Ambulatory Medical Care Surveys was used. We selected 1125 visits by patients with atrial fibrillation, including 877 visits to cardiologists and primary care physicians in which apparent contraindications for anticoagulation were absent. The principal outcome measure was the proportion of visits with warfarin reported. We analyzed trends in warfarin use and statistically evaluated the predictors of warfarin use. Warfarin use increased from 13% of atrial fibrillation visits in 1989 to 40% in 1993 (P for trend <.001) in patients without contraindications. Between 1993 and 1996, however, there was no change in warfarin use. Independent of other factors, warfarin was significantly more likely to be reported in patients with a history of stroke and in patients residing outside of the South.ConclusionsWarfarin use in atrial fibrillation has not increased recently, indicating inadequate implementation of this highly effective therapy. Barriers to anticoagulation in real-world clinical practice need to be identified and addressed. (Circulation. 1998;97:1231-1233.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundImprovement in endothelial function may be an important mechanism by which estrogen replacement therapy protects postmenopausal women against coronary artery disease. However, combined hormone replacement therapy is more frequently used owing to the risk of uterine cancer with estrogen-only therapy. Concurrent progesterone treatment may attenuate the beneficial effects of estrogens not only on the lipid profile but also on the endothelium.Methods and Results-We studied endothelial vasomotor function in 100 healthy postmenopausal women aged 53.3 +/- 2.9 years randomized to either combined hormone replacement therapy (n=46) or no substitution (n=54) 2.9 +/- 0.5 years earlier. In addition, 30 healthy premenopausal women aged 30.3 +/- 4.2 years were studied. With external ultrasound, brachial artery diameter was measured at rest, during reactive hyperemia (with increased flow causing endothelium-dependent dilation), and after sublingual nitroglycerin (causing endothelium-independent dilation). Compared with premenopausal women, flow-mediated dilation was significantly reduced in both postmenopausal groups. In the postmenopausal women, total cholesterol was lower in the treated women (5.66 +/- 0.83 versus 6.13 +/- 0.92 mmol/L; P=.025), whereas HDL cholesterol was similar (1.91 +/- 0.53 versus 1.85 +/- 0.46 mmol/L; P=NS). Dilation to flow and to nitroglycerin was similar in the two postmenopausal groups (flow: 2.5 +/- 2.9% versus 2.2 +/- 2.2%, P=NS; nitrate: 18.7 +/- 5.9% versus 17.2 +/- 6.2%, P=NS).ConclusionsLong-term combined oral hormone replacement therapy is without beneficial effects on endothelial vasomotor function in healthy postmenopausal women. This supports the view that progesterone may attenuate the beneficial effects of unopposed estrogen replacement. (Circulation. 1998;97:1234-1238.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundThe evolving technique of carotid stenting is being evaluated as an alternative to endarterectomy. Identification of the factors that predispose a patient to neurological complications would facilitate further refinement of the technique and optimize patient selection.Methods and Results-We analyzed the impact of various clinical, morphological, and procedural determinants on the development of procedural strokes in 231 patients who underwent elective (primary) stenting of 271 extracranial carotid arteries. The mean age of the patients was 68.7 +/- 10 years, 165 (71%) were males, and 139 (60%) had symptoms attributed to the lesion treated. This series represented a high-risk subset with 164 patients (71%) having significant coronary artery disease, 91 (39%) having bilateral disease, and 28 (12%) having contralateral carotid occlusion. Of the treated vessels, 59 (22%) had prior carotid endarterectomy, 66 (24%) had ulcerated plaques, and 87 (32%) had calcified lesions. Only 37 treated vessels (14%) would have been eligible for inclusion in the North American Symptomatic Carotid Endarterectomy Trial (NASCET). There were 17 (6.2%) minor and 2 (0.7%) major strokes during and within 30 days of the procedure. NASCET-eligible patients had a low (2.7%) risk of procedural strokes after carotid stenting. The results of multivariate analysis revealed advanced age (P=.006) and presence of long or multiple stenoses (P=.006) as independent predictors of procedural strokes.ConclusionsDuring this procedural developmental phase of carotid stenting, neurological complications were highly dependent on patient selection. Advanced age and long or multiple stenoses were independent predictors of procedural stroke. (Circulation. 1998;97:1239-1245.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundThe frequency of, course of, and factors associated with cardiovascular abnormalities in pediatric HIV are incompletely understood.Methods and Results-A baseline echocardiogram (median age, 2.1 years) and 2 years of follow-up every 4 months were obtained as part of a prospective study on 196 vertically HIV-infected children. Age- or body surface area-adjusted z scores were calculated by use of data from normal control subjects. Although 88% had symptomatic HIV infection, only 2 had CHF at enrollment, with a 2-year cumulative incidence of 4.7% (95% CI, 1.5% to 7.9%). All mean cardiac measurements were abnormal at baseline (decreased left ventricular fractional shortening [LV FS] and contractility and increased heart rate and LV dimension, mass, and wall stresses). Most of the abnormal baseline cardiac measurements correlated with depressed CD4 cell count z scores and the presence of HIV encephalopathy. Heart rate and LV mass showed significantly progressive abnormalities, whereas FS and contractility tended to decline. No association was seen between longitudinal changes in FS and CD4 cell count z score. Children who developed encephalopathy during follow-up had depressed initial FS, and FS continued to decline during follow-up.ConclusionsSubclinical cardiac abnormalities in HIV-infected children are common, persistent, and often progressive. Dilated cardiomyopathy (depressed contractility and dilatation) and inappropriate LV hypertrophy (elevated LV mass in the setting of decreased height and weight) were noted. Depressed LV function correlated with immune dysfunction at baseline but not longitudinally, suggesting that the CD4 cell count may not be a useful surrogate marker of HIV-associated LV dysfunction. However, the development of encephalopathy may signal a decline in FS. (Circulation. 1998;97:1246-1256.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundTwo populations of T cells contribute to allograft rejection. T cells with direct allospecificity are activated after recognition of intact MHC alloantigens displayed at the surface of donor passenger leukocytes carried within the graft. In contrast, T cells with indirect allospecificity recognize donor alloantigens as processed peptides associated with self (recipient)-MHC class II molecules. In small animal models of transplantation, direct pathway T cells dominate the acute rejection process and are rendered tolerant to the graft after the loss of donor passenger leukocytes. It has been argued that indirect pathway T cells contribute substantially to continual graft damage after passenger cell loss. The purpose of this study was to determine whether donor-specific tolerance could be detected in T cells with direct anti-donor allospecificity in human heart transplant recipients after prolonged graft residence.1:100 000, it was significantly lower than that estimated against the third-party control.ConclusionsDonor-specific hyporesponsiveness is demonstrated in 50% of recipients in both the HTLf and CTLf compartments of the direct alloresponse. Direct allorecognition therefore appears unlikely to be responsible for the progression of chronic rejection, implicating indirect allorecognition as the predominant immunological driving force. Furthermore, these data have potential implications for graft outcome, adjustment of immunosuppression, and recipient monitoring. (Circulation. 1998;97:1257-1263.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundLong-QT syndrome (LQTS) is an inherited cardiac arrhythmia that causes sudden death in young, otherwise healthy people. Four genes for LQTS have been mapped to chromosome 11p15.5 (LQT1), 7q35-36 (LQT2), 3p21-24 (LQT3), and 4q25-27 (LQT4). Genes responsible for LQT1, LQT2, and LQT3 have been identified as cardiac potassium channel genes (KVLQT1, HERG) and the cardiac sodium channel gene (SCN5A).Methods and Results-After studying 115 families with LQTS, we used single-strand conformation polymorphism (SSCP) and DNA sequence analysis to identify mutations in the cardiac potassium channel gene, KVLQT1. Affected members of seven LQTS families were found to have new, previously unidentified mutations, including two identical missense mutations, four identical splicing mutations, and one 3-bp deletion. An identical splicing mutation was identified in affected members of four unrelated families (one Italian, one Irish, and two American), leading to an alternatively spliced form of KVLQT1. The 3-bp deletion arose de novo and occurs at an exon-intron boundary. This results in a single base deletion in the KVLQT1 cDNA sequence and alters splicing, leading to the truncation of KVLQT1 protein.ConclusionsWe have identified LQTS-causing mutations of KVLQT1 in seven families. Five KVLQT1 mutations cause the truncation of KVLQT1 protein. These data further confirm that KVLQT1 mutations cause LQTS. The location and character of these mutations expand the types of mutation, confirm a mutational hot spot, and suggest that they act through a loss-of-function mechanism or a dominant-negative mechanism. (Circulation. 1998;97:1264-1269.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID