ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background—Mental stress is a risk factor for atherosclerosis and may precipitate myocardial ischemia and infarction. Because endothelial dysfunction is an early manifestation of atherosclerosis, we investigated the impact of mental stress on endothelial function.Methods and Results—The effects of a 3-minute mental stress task on endothelium-dependent vasodilation were studied in healthy subjects without cardiovascular risk factors. Flow-mediated (FMD) and nitroglycerin (0.4 mg sublingual)-induced vasodilation were studied before and after mental stress by high-resolution ultrasound of the radial artery. Additionally, FMD was assessed before and 10 to 45 minutes after mental stress during intraarterial infusion of a selective endothelin A receptor antagonist (BQ-123, 1 nmol/min) or saline, respectively. Endothelium-dependent vasodilation was reduced by half for about 45 minutes (8.0±1.1% versus 4.1±1.0%;P<0.002), whereas endothelium-independent vasodilation to nitroglycerin remained unaffected (15.6±1.6 versus 14.3±1.3%; NS). Intraarterial infusion of BQ-123, a selective endothelin-A receptor antagonist, but not saline prevented the impairment of endothelium-dependent vasodilation (8.6±1.2 versus 9.4±1.3%; NS). In contrast, intraarterial infusion of norepinephrine of similar duration as mental stress did not inhibit FMD.Conclusions—Mental stress induces prolonged endothelial dysfunction, which is prevented by selective endothelin-A receptor antagonism. This represents a novel and important link between mental stress and atherosclerotic vascular disease.

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background—Despite extensive proximal ablation, all potentials frequently cannot be eliminated from the left pulmonary veins (PV).Methods and Results—PV electrograms were analyzed during sinus rhythm, coronary sinus, and left atrial appendage (LAA) pacing, and PV and LAA angiography performed. During pacing, an initial low-amplitude slow potential was recorded on the anterior aspect of the left superior PV and anticipated with shortest activation time by LAA pacing. Its timing coincided with posterior LAA activation, shown to be immediately adjacent to the left superior PV by angiography. In the left inferior PV, the first potential was smaller and less sharp, coinciding with adjacent low LA activation. Angiographically, the LAA was at least 15 mm from the left inferior PV. The second sharper potential in both left PVs was eliminated by proximal ablation.Conclusion—Far field LAA activity consistently adds to PV myocardial electrograms in the left superior PV whereas lower, less sharp extravenous potentials in the left inferior PV originate from the inferior LA. They can be identified by LAA and coronary sinus pacing.

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background—Mild renal insufficiency is associated with an increased risk for cardiovascular events in women with coronary artery disease (CAD). However, the relationship between mild renal insufficiency and atherosclerotic CAD in women is not known.Methods and Results—Women with chest pain who were referred for coronary angiography in the NHLBI Women’s Ischemia Syndrome Evaluation (WISE) study underwent quantitative coronary angiography, blood measurements of creatinine, lipids, and homocysteine, and assessment of CAD risk factors. Fifty-six women had mild renal insufficiency (serum creatinine 1.2 to 1.9 mg/dL), and 728 had normal renal function (creatinine <1.2 mg/dL). Creatinine correlated with angiographic CAD severity score (r=0.11,P<0.004) and maximum coronary artery stenosis (r=0.11,P<0.003). Compared with women with normal renal function, those with mild renal insufficiency were more likely to have significant angiographic CAD (≥50% diameter stenosis in ≥1 coronary artery) (61% versus 37%;P<0.001) and CAD in multiple vessels (P<0.001 for association) and had greater maximum percent diameter coronary stenosis (59±35% versus 38±36%;P<0.001). Mild renal insufficiency was associated with significant angiographic CAD independent of age and risk factors (OR=1.9, 95%CI=1.1 to 3.5). After controlling for homocysteine in 509 women, mild renal insufficiency remained predictive of CAD (OR=3.2, 95%CI=1.4 to 7.2).Conclusions—In women with chest pain, mild renal insufficiency is an independent predictor of significant angiographic CAD. Mildly increased serum creatinine is probably a marker for unmeasured proatherogenic factors.

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background—Defective protein trafficking is a consequence of gene mutations. Human long-QT (LQT) syndrome results from mutations in several genes, including thehuman ether-a-go-go-related gene(HERG), which encodes a delayed rectifier K+current. Trafficking-defective mutant HERG protein is a mechanism for reduced delayed rectifier K+current in LQT2, and high-affinity HERG channel-blocking drugs can result in pharmacological rescue.Methods and Results—We postulated that drug molecules modified to remove high-affinity HERG block may still stabilize mutant proteins in a conformation required for rescue. We tested terfenadine carboxylate (fexofenadine) and terfenadine, structurally similar drugs with markedly different affinities for HERG block, for rescue of trafficking-defective LQT2 mutations. Terfenadine rescued the N470D mutation but blocked the channels. In contrast, fexofenadine rescued N470D with a half-maximal rescue concentration of 177 nmol/L, which is ≈350-fold lower than the half-maximal channel block concentration. The G601S mutation was also rescued without channel block.Conclusions—Pharmacological rescue can occur without channel block. This could represent a new antiarrhythmic paradigm in the treatment of some trafficking-defective LQT2 mutations.

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID