ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundFailing human myocardium is characterized by abnormal relaxation, a deficient sarcoplasmic reticulum (SR) Ca2+uptake, and a negative frequency response, which have all been related to a deficiency in the SR Ca2+ATPase (SERCA2a) pump.Methods and ResultsTo test the hypothesis that an increase in SERCA2a could improve contractile function in cardiomyocytes, we overexpressed SERCA2a in human ventricular myocytes from 10 patients with end-stage heart failure and examined intracellular Ca2+handling and contractile function. Overexpression of SERCA2a resulted in an increase in both protein expression and pump activity and induced a faster contraction velocity (26.7±6.7% versus 16.6±2.7% shortening per second,P<0.005) and enhanced relaxation velocity (32.0±10.1% versus 15.1±2.4%,P<0.005). Diastolic Ca2+was decreased in failing cardiomyocytes overexpressing SERCA2a (270±26 versus 347±30 nmol/L,P<0.005), whereas systolic Ca2+was increased (601±38 versus 508±25 nmol/L,P<0.05). In addition, the frequency response was normalized in cardiomyocytes overexpressing SERCA2a.ConclusionsThese results support the premise that gene-based therapies and targeting of specific pathways in human heart failure may offer a new modality for the treatment of this disease.

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundAngiotensin-converting enzyme (ACE) inhibitors are generally prescribed by physicians in doses lower than the large doses that have been shown to reduce morbidity and mortality in patients with heart failure. It is unclear, however, if low doses and high doses of ACE inhibitors have similar benefits.Methods and ResultsWe randomly assigned 3164 patients with New York Heart Association class II to IV heart failure and an ejection fraction ≤30% to double-blind treatment with either low doses (2.5 to 5.0 mg daily, n=1596) or high doses (32.5 to 35 mg daily, n=1568) of the ACE inhibitor, lisinopril, for 39 to 58 months, while background therapy for heart failure was continued. When compared with the low-dose group, patients in the high-dose group had a nonsignificant 8% lower risk of death (P=0.128) but a significant 12% lower risk of death or hospitalization for any reason (P=0.002) and 24% fewer hospitalizations for heart failure (P=0.002). Dizziness and renal insufficiency was observed more frequently in the high-dose group, but the 2 groups were similar in the number of patients requiring discontinuation of the study medication.ConclusionsThese findings indicate that patients with heart failure should not generally be maintained on very low doses of an ACE inhibitor (unless these are the only doses that can be tolerated) and suggest that the difference in efficacy between intermediate and high doses of an ACE inhibitor (if any) is likely to be very small.

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundMales have an earlier onset and greater prevalence of clinical atherosclerosis than age-matched females, which is consistent with an atheroprotective effect of the female sex steroids, estrogen and progesterone. We therefore examined the effects of estrogen and progesterone on human foam cell formation, a key early event in atherogenesis.Methods and ResultsMonocytes from healthy female and male donors were obtained from white cell concentrates and allowed to differentiate into macrophages over 10 days. These human monocyte-derived macrophages (MDMs) were exposed to either control (0.1% vol/vol ethanol) or estrogen or progesterone treatment on days 3 through 10. Lipid loading was achieved on days 8 through 10 by incubation with acetylated LDL. Lipid from the MDMs was then extracted for analysis of cholesteryl ester (CE) content. 17β-Estradiol at both physiological (2 nmol/L) and supraphysiological (20 and 200 nmol/L) concentrations produced a significant reduction in macrophage CE content (88±3%, 88±2%, and 85±4%, respectively;P<0.02 compared with control). Physiological and supraphysiological levels of progesterone (2, 10, and 200 nmol/L) produced an even more dramatic reduction in CE content (74±9%, 56±10%, and 65±8%, respectively;P<0.002 compared with control). This effect could be abrogated by coincubation with the progesterone receptor antagonist RU486. Neither estrogen nor progesterone produced a reduction in lipid loading in male-donor-derived MDMs. Detailed lipid trafficking studies demonstrated that both estrogen and progesterone altered macrophage uptake and/or processing of modified LDL.ConclusionsPhysiological levels of estrogen and progesterone are associated with a female-sex-specific reduction in human macrophage lipid loading, which is consistent with an atheroprotective effect.

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThere is controversy about the association betweenHelicobacter pyloriinfection and manifestations of coronary heart disease (CHD), the potential role of the more virulentH pyloristrains, and whether or not a positive serostatus is related to increased levels of markers of systemic inflammation.Methods and ResultsWe assessed the prevalence of an infection withH pyloriand in particular the anti-cytotoxin-associated protein A (CagA) antibody response of the more virulent strains expressing CagA in 312 patients with stable CHD and in 479 control subjects. Serological prevalence ofH pyloriinfection (IgG titer) was significantly higher in patients than in control subjects after adjustment for age and sex (44.2% versus 31.3%,P<0.001). After adjustment for various covariates in multiple logistic regression, the odds ratio (OR) for CHD was 1.3 (95% CI, 0.9 to 1.9) given a positive IgG serostatus. The prevalence of CagA-positive strains was 27.9% in patients and 21.7% in control subjects (P=0.076 adjusted for age and sex). The OR for CHD in the fully adjusted model was 1.1 (95% CI, 0.7 to 1.7). None of the inflammatory markers (C-reactive protein, fibrinogen, plasma viscosity, or leukocytes) was significantly different according to serostatus.ConclusionsIn this large case-control study, the association ofH pyloriinfection with stable CHD was strongly reduced and was no longer statistically significant after controlling for potential confounders. We also found no independent association between the more virulent strains and CHD. In addition, a positive serostatus was not associated with a systemic inflammatory response. Thus, these data do not support the hypothesis that infection withH pylorimight be a major risk factor for stable CHD.

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundPatients with obstructive sleep apnea (OSA) have high levels of muscle sympathetic nerve activity (MSNA). We tested the hypothesis that long-term continuous positive airway pressure (CPAP) treatment will decrease MSNA in OSA patients.Methods and ResultsWe measured blood pressure, heart rate, and MSNA in 11 normotensive, otherwise healthy patients with OSA who were treated with CPAP. The measurements were obtained at baseline and after 1 month, 6 months, and 1 year of CPAP treatment. These measurements were compared with those recorded in 9 otherwise healthy OSA patients who were not treated with CPAP for 1 year. In both untreated and treated patients, blood pressure and heart rate did not change over time. MSNA was similar during repeated measurements in the untreated group. By contrast, MSNA decreased significantly over time in patients treated with CPAP. This decrease was evident after both 6 months and 1 year of CPAP treatment (P=0.02 for both).ConclusionsCPAP treatment decreases muscle sympathetic traffic in patients with OSA. This effect of CPAP is evident only after an extended duration of therapy.

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Backgroundα1-adrenergic receptors (α1ARs) regulate blood pressure, regional vascular resistance, and venous capacitance; the exact subtype (α1a, α1b, α1d) mediating these effects is unknown and varies with species studied. In order to understand mechanisms underlying cardiovascular responses to acute stress and chronic catecholamine exposure (as seen with aging), we tested two hypotheses: (1) human α1AR subtype expression differs with vascular bed, and (2) age influences human vascular α1AR subtype expression.Methods and ResultsFive hundred vessels from 384 patients were examined for α1AR subtype distribution at mRNA and protein levels (RNase protection assays, ligand binding, contraction assays). Overall vessel α1AR density is 16±2.3fmol/mg total protein. α1aAR predominates in arteries at mRNA (P<0.001) and protein (P<0.05) levels; all 3 subtypes are present in veins. Furthermore, α1AR mRNA subtype expression varies with vessel bed (α1ahigher in splanchnic versus central arteries,P<0.05); competition analysis (selected vessels) and functional assays demonstrate α1aand α1b-mediated mammary artery contraction. Overall α1AR expression doubles with age (<55 versus ≥65 years) in mammary artery (no change in saphenous vein), accompanied by increased α1b>α1aexpression (P≤0.001).ConclusionsHuman vascular α1AR subtype distribution differs from animal models, varies with vessel bed, correlates with contraction in mammary artery, and is modulated by aging. These findings provide potential novel targets for therapeutic intervention in many clinical settings.

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe Telectronics Accufix pacing leads were recalled in November 1994 after 2 deaths and 2 nonfatal injuries were reported. This multicenter clinical study (MCS) of patients with Accufix leads was designed to determine the rate of spontaneous injury related to the J retention wire and results of lead extraction.Methods and ResultsThe MCS included 2589 patients with Accufix atrial pacing leads that were implanted at or who were followed up at 12 medical centers. Patients underwent cinefluoroscopic imaging of their lead every 6 months. The risk of J retention wire fracture was ≈5.6%/y at 5 years and 4.7%/y at 10 years after implantation. The annual risk of protrusion was 1.5%. A total of 40 spontaneous injuries were reported to a worldwide registry (WWR) that included data from 34 672 patients (34 892 Accufix leads), including pericardial tamponade (n=19), pericardial effusion (n=5), atrial perforation (n=3), J retention wire embolization (n=4), and death (n=6). The risk of injury was 0.02%/y (95% CI, 0.0025 to 0.072) in the MCS and 0.048%/y (95% CI, 0.035 to 0.067) in the WWR. A total of 5299 leads (13%) have been extracted worldwide. After recall in the WWR, fatal extraction complications occurred in 0.4% of intravascular procedures (16 of 4023), with life-threatening complications in 0.5% (n=21). Extraction complications increased with implant duration, female sex, and J retention wire protrusion.ConclusionsAccufix pacing leads pose a low, ongoing risk of injury. Extraction is associated with substantially higher risks, and a conservative management approach is indicated for most patients.

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID