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:

BackgroundChronic heart failure is associated with induction of secondary inflammatory mediators, including prostanoids. The latter exert diverse functional and morphological effects on cardiac myocytes. Induction of cyclooxygenase (COX), the enzyme responsible for generating prostanoids, requires activation of nuclear factor-kappa B (NF-kappa B). The aim of the present study was to determine the expression of COX-2 and activation of NF-kappa B in the failing human heart.Methods and Results-Myocardial tissue from 27 patients with end-stage heart failure (various etiologies: ischemic heart disease, n=16; idiopathic dilated cardiomyopathy, n=10; and valvular heart disease, n=1), 2 septic patients, and 8 normal control subjects was immunostained with antisera to COX-2 and NF-kappa B. Western blotting was performed and showed high anti-COX-2 antibody specificity and the presence of COX-2 protein in the sample tissues. In situ hybridization and immunohistochemistry showed little or no expression of COX-2 and NF-kappa B in the control hearts. In contrast, there was abundant expression of COX-2 mRNA and protein in myocytes and inflammatory cells in areas of fibrotic scar compared with regions of normal morphology in all cases of heart failure, except the cases with sepsis, which showed an abundance of COX-2 throughout the myocardium. Sites of NF-kappa B activation were associated with those of COX-2 expression.ConclusionsWe demonstrate induction of COX-2 and activation of NF-kappa B in the myocardium of failing human hearts. Induction of both molecules appears to be associated with the presence of inflammation and scar formation.(Circulation. 1998;98:100-103.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundOur rationale for this study was to analyze the risk for procedural failure of attempted stenting and the risk for major adverse cardiac events (MACE) after success and to develop a risk stratification protocol for successful procedures.Methods and Results-Stenting was attempted in 2894 procedures during the 5-year study period (success in 98.3% of 3815 lesions). After failure, the MACE rate was 42.6%. The risk for failure was higher for lesions in the left circumflex coronary artery or in venous bypass grafts and after an acute occlusion before stenting; it increased with stenosis length or grade and decreased with vessel size and growing institutional experience in stenting. After success, death occurred in 0.8%, death or myocardial infarction in 2.0%, and any MACE in 3.6%. Independent risk factors for MACE were older age, diabetes, acute myocardial infarction, unstable angina, impaired left ventricular function, residual dissections, stent overlap, longer stented segments, and a postprocedural regimen without ticlopidine. Procedural factors were substantially stronger predictors than operator-independent variables available before procedures. Overall, the risk declined after the first 3 days. Two major factors exhibited time-dependent variations of their influence: while residual dissections were the dominant risk factor within the first 3 days with a reduction after that, no protective effect of ticlopidine could be identified before day 3. From these results, we derived a risk stratification protocol for individual procedures.ConclusionsThese results underscore the importance of optimal angiographic results and the need for antiplatelet regimens with immediate onset. Our risk stratification protocol may guide individual postprocedural care and allow us to compare risk profiles of different study populations and to devise quality control programs for stenting. (Circulation. 1998;98:104-111.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundIntravascular ultrasound (IVUS) studies have demonstrated that stents are frequently suboptimally expanded despite the use of high pressures for deployment. The purpose of this study was to identify the mechanisms responsible for such residual lumen stenosis.Methods and Results-Fifty-seven lesions from 50 patients treated with high-pressure (median +/- interquartile range, 14 +/- 2 atm) elective (44 de novo, 13 restenotic lesions) stenting were prospectively studied (29 Wiktor, Medtronic; 28 Palmaz-Schatz, Cordis Corp). Balloon subexpansion was calculated as the difference between maximal and minimal balloon cross-sectional areas at peak pressure measured by automatic edge detection; elastic recoil was calculated as the difference between minimal measured balloon size and IVUS-derived minimal lumen area within the stent. Angiographic residual diameter stenosis was 10 +/- 13% (reference diameter, 3.1 +/- 0.7 mm; balloon to artery ratio, 1.12 +/- 0.23) and IVUS-derived stent expansion was 80 +/- 28%. However, although balloon nominal size was 9.6 +/- 1.3 mm2and maximal balloon size measured inside the coronary lumen was 12.5 +/- 3.2 mm2, final stent minimal lumen area was only 7.1 +/- 2.2 mm2. Balloon subexpansion of 4.0 +/- 1.8 mm2(33%) and elastic recoil of 1.6 +/- 2.3 mm2(20%) (both P<0.0001) were the two mechanisms responsible for residual luminal stenosis. Wiktor stent and peak inflation pressure correlated with balloon subexpansion, whereas Wiktor stent, de novo lesion, and minimal lumen area at baseline correlated with elastic recoil.ConclusionsDespite high-pressure deployment, lumen dimensions after stenting are only 57% of maximal achievable. Inadequate balloon expansion and elastic recoil are responsible for residual lumen stenosis, suggesting that plaque characteristics and stent resistance deserve further investigation. (Circulation. 1998;98:112-118.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundThe effect of long-term smoking on coronary vasomotion and vasodilator capacity in healthy smokers is unknown.Methods and Results-Myocardial blood flow (MBF) was quantified with [(13) N]ammonia and positron emission tomography (PET) at rest, during cold pressor testing (endothelium-dependent vasomotion), and during dipyridamole-induced hyperemia in 16 long-term smokers and 17 nonsmokers. MBF at rest did not differ between the 2 groups. Cold induced similar increases in rate-pressure product (RPP) in smokers and nonsmokers. However, MBF increased only in nonsmokers and was, during cold, higher than in smokers (0.91 +/- 0.18 versus 0.78 +/- 0.14 mL [middle dot] g-1[middle dot] min-1, P<0.05). MBF normalized to the RPP (derived from the ratio of MBF ([milliliters per gram per minute] to RPP [beats per minute times millimeters of mercury] times 10 000) declined in smokers but remained unchanged in nonsmokers (0.86 +/- 0.10 versus 0.72 +/- 0.11, P=0.0006, and 0.99 +/- 0.25 versus 0.96 +/- 0.27, P=NS). The hyperemic response to dipyridamole and the myocardial flow reserve did not differ between the 2 groups. In a multiple regression model adjusted for age, sex, serum lipid levels, years of smoking, and pack-years, years of smoking was the strongest predictor of the normalized blood flow response to cold (P<0.001), followed by the HDL/LDL ratio.ConclusionsThe normal hyperemic response to dipyridamole in long-term smokers indicates a preserved endothelium-independent coronary vascular smooth muscle relaxation, whereas the abnormal response to cold suggests a defect in coronary vasomotion likely located at the level of the coronary endothelium. Its severity depends on the total exposure time to smoking. (Circulation. 1998;98:119-125.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundLow-dose dopamine is frequently used in patients in the intensive care setting. Dopamine may inhibit chemoreceptor afferents and hence decrease chemoreflex sensitivity to hypoxia.Methods and Results-In a double-blind, randomized, crossover study, we determined the effects of dopamine (5 [micro sign]g [middle dot] kg-1[middle dot] min (-1)) and placebo infusion on oxygen saturation, minute ventilation, and sympathetic nerve activity during normoxia and 5 minutes of hypoxia in 10 normal young subjects. We further investigated the effects of dopamine and placebo on minute ventilation during normoxic breathing in 8 patients with severe heart failure and in 8 age-matched control subjects. Dopamine did not decrease minute ventilation during normoxia in normal subjects. During hypoxia, minute ventilation was 12.9 +/- 1.3 L/min on dopamine and 15.8 +/- 1.5 L/min on placebo (P<0.0001). Oxygen saturation during hypoxia was lower with dopamine (78 +/- 3%) than placebo (84 +/- 2%; P<0.0001). Sympathetic nerve activity during hypoxia was not enhanced with dopamine despite the lower O2saturation. Subjects were able to maintain a voluntary apnea to a lower oxygen saturation on dopamine than on placebo (P<0.05). In heart failure patients breathing room air, but not in age-matched control subjects, dopamine decreased minute ventilation despite decreased oxygen saturation and increased PETCO2during dopamine (all P<or=to0.02).ConclusionsDopamine inhibits chemoreflex responses during hypoxic breathing in normal humans, preferentially affecting the ventilatory response more than the sympathetic response. Dopamine also depresses ventilation in normoxic heart failure patients breathing room air. Ventilatory inhibition by low-dose dopamine may adversely influence outcome in hypoxic patients, especially in patients with heart failure. (Circulation. 1998;98:126-131.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundRecent reports have suggested that excessive amounts of endogenous NO may contribute to the myocardial dysfunction and injury in heart failure. In the present report, we investigate the cellular expression and activity of endothelial (eNOS) and inducible (iNOS) NO synthase in failing human hearts with special reference to the underlying lesion and drug therapy.Methods and Results-Myocardial tissues were obtained from 28 failing human hearts with various pathogeneses and 4 nonfailing hearts as controls. Only weak or focal expression of both eNOS and iNOS was seen in ventricles of nonfailing hearts. In failing hearts, immunoreactivity and hybridization signals for eNOS were increased only in cardiac myocytes of subendocardial areas. Signals for iNOS in cardiac myocytes were consistently seen in heart failure of various pathogeneses and were apparent in both infarcted and noninfarcted regions of ischemic cardiomyopathy. Apparent signals for iNOS were also seen in infiltrating macrophages in infarcted regions of ischemic cardiomyopathy, myocarditis, and septic hearts. The expression of eNOS but not iNOS in the myocytes was intimately associated with beta-adrenergic therapy before the operation, being more abundant in patients on beta-blockers compared with diminished presence in patients on beta-agonists. In contrast to immunohistochemical data, iNOS activity was more variable than constitutive NOS activity and correlated significantly with the density of infiltrating macrophages.ConclusionsThese results suggest that whereas increased eNOS and/or iNOS expression in failing cardiac myocytes may in general contribute to myocardial dysfunction, myocyte injury or death associated with inflammatory lesions may be caused in part by abundant iNOS expression within infiltrating macrophages rather than cardiac myocytes. (Circulation. 1998;98:132-139.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundCardiac effects of hypertension include increased left ventricular (LV) mass and LV hypertrophy, as well as increased left atrial size, a predictor of stroke and atrial fibrillation. Although literature on reduction of LV mass with antihypertensive therapy is extensive, little information is available on effects of treatment on left atrial size.Methods and Results-Patients with mild to moderate hypertension (diastolic blood pressure 95 to 109 mm Hg) were randomly allocated to treatment with atenolol, captopril, clonidine, diltiazem, hydrochlorothiazide, or prazosin in a double-masked trial. Two-dimensional targeted M-mode echocardiography was used to assess left atrial size and LV mass at baseline, 8 weeks, and 1 and 2 years. Longitudinal analysis examined changes in left atrial size from the baseline study, statistically adjusting for age, race, pretreatment left atrial size and LV mass, and serial measurements of systolic blood pressure, body weight, urinary sodium excretion, and physical activity score. Without adjustment for covariates, only hydrochlorothiazide was associated with decreases in left atrial size from baseline at 8 weeks (-1.0 +/- 5.2 mm; P=0.052), 1 year (-2.0 +/- 5.1 mm; P=0.02), and 2 years (4.6 +/- 7.2 mm; P=0.002). After adjustment for effects of covariates, patients with normal left atrial size had greater reduction (-3.3 mm) in left atrial size at 2 years with hydrochlorothiazide than with any other drug. For patients with left atrial enlargement, left atrial size decreased significantly with hydrochlorothiazide, atenolol, clonidine, and diltiazem at 1 year and with all treatments at 2 years. However, reduction at 2 years was greater with hydrochlorothiazide than with captopril or prazosin.ConclusionsAntihypertensive drugs differ in their effects on left atrial size. Hydrochlorothiazide was associated with greater overall reduction of left atrial size than other drugs effective for the treatment of hypertension. Reduction of left atrial size with therapy is in part independent of factors known to influence left atrial size, including LV mass and reduction of LV mass with treatment. The clinical benefit of reducing left atrial size with antihypertensive treatment remains to be determined. (Circulation. 1998;98:140-148.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundA large transmural myocardial infarction may initiate structural and geometric changes in the left ventricle that are commonly referred to as remodeling. Progressive, adverse remodeling of the myocardium may lead to ventricular dilatation and congestive heart failure. Recent studies have highlighted the effects of some cytokines on immune-mediated myocyte injury, postischemic myocardial inflammation, and cardiac function. However, studies of the involvement of cytokines in remodeling of the heart are few.Methods and Results-In a rat model of myocardial infarction, progressive dilatation of the left ventricular cavity and lack of appropriate hypertrophy of the surviving myocardium were confirmed by transthoracic echocardiography. The relative expression of mRNA for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6 in the infarcted and noninfarcted myocardium of these rats, as well as in a group of sham-operated animals, was assessed by the technique of quantitative polymerase chain reaction amplification. In the infarcted region, TNF-alpha, IL-1 beta, and IL-6 gene expression peaked at 1 week after infarction and decreased rapidly thereafter. In contrast, at 20 weeks after infarction, the gene expression levels of these cytokines remained significantly higher in the noninfarcted than in the infarcted zone or in the myocardium of sham-operated animals. Furthermore, the levels of these cytokines in the noninfarcted region correlated with the left ventricular end-diastolic diameter measured at 8 and 20 weeks after infarction. Among these cytokines, IL-1 beta expression was highest, and its level correlated well with collagen deposition in the noninfarcted myocardium at 8 and 20 weeks after surgery. At 20 weeks after infarction, immunohistochemical analysis revealed the presence of IL-1 beta in macrophages, endothelial cells, and vascular smooth muscle cells in the noninfarcted region, whereas no such immunoreactivity was found in the myocardium of sham-operated animals.ConclusionsThese findings suggest the possible involvement of cytokines during the remodeling process of the noninfarcted left ventricular myocardium. (Circulation. 1998;98:149-156.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID