摘要:

BackgroundAlthough hormone replacement therapy has been associated with reduction of cardiovascular events in postmenopausal women, the mechanisms that mediate this apparent benefit are unclear. Because improvement in vaso-motor function may represent one of the beneficial effects of estrogen administration, we investigated the acute effects of physiological levels of estrogen on the vascular responses of estrogen-deficient postmenopausal women.Methods and ResultsThe study included 40 postmeno-pausal women 60±8 years old (mean±SD), 20 of whom had one or more conditions associated with vascular dysfunction (hypertension, hypercholesterolemia, diabetes, or coronary artery disease). The forearm vascular responses to the endo-thelium-dependent vasodilator acetylcholine were studied before and during infusion of 17β-estradiol into the ipsilateral brachial artery. In 31 subjects, the effect of estradiol on the responses to the endothelium-independent vasodilator sodium nitroprusside was also studied. Women with risk factors for vascular dysfunction had significantly reduced vasodilator responses to acetylcholine (P=.01) and to sodium nitroprusside (P<.001) compared with healthy subjects. Intra-arterial infusion of 17β-estradiol increased the forearm venous estradiol concentration from 16±10 to 318±188 pg/mL, levels typical of reproductive-age women at midcycle, but caused no vasodilation. However, estradiol potentiated the forearm vasodilation induced by acetylcholine by 18±30% (P<.001) in women with risk factors for vascular dysfunction and by 14±23% (P=.03) in healthy women. Estradiol also potentiated the forearm vasodilation induced by sodium nitroprusside in women with risk factors for vascular dysfunction by 14±21% (P<.001) but not in healthy women.ConclusionsPhysiological levels of 17,3-estradiol selectively potentiate endothelium-dependent vasodilation in healthy postmenopausal women and potentiate both endothelium-dependent and endothelium-independent vasodilation in post-menopausal women with risk factors for atherosclerosis and evidence of impaired vascular function. These vascular effects may be partly responsible for the long-term benefit of estrogen therapy on cardiovascular events in postmenopausal women.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundAortic counterpulsation has been observed to reduce the rate of reocclusion of the infarct-related artery after patency has been restored during acute myocardial infarction in observational studies. To evaluate the benefit-to-risk ratio of aortic counterpulsation during the early phase of myocardial infarction, a multicenter randomized clinical trial was performed.Methods and ResultsPatients who had patency restored during acute cardiac catheterization within the first 24 hours of onset of myocardial infarction were randomly assigned to aortic counterpulsation for 48 hours versus standard care. Intravenous heparin was used similarly in both groups and was continued for a median (25th, 75th percentile) of 5 (2,7) days. A total of 182 patients were enrolled; 96 were assigned to aortic counterpulsation and 86 to standard care. Repeat cardiac catheterization was performed at a median of 5 (4,6) days after randomization in 89% of patients assigned to aortic counterpulsation and in 90% of control patients. Patients randomized to aortic counterpulsation had similar rates of severe bleeding complications (2% versus 1%), number of units of blood transfused (mean, 1.3±2.6 versus 0.9±1.8 units), and vascular repair or thrombectomy (5% versus 2%) compared with patients treated in a conventional manner. Patients randomized to aortic counterpulsation had significantly less reocclusion of the infarct-related artery during follow-up compared with control patients (8% versus 21%,P<.03). In addition, there was a significantly lower event rate in patients assigned to aortic counterpulsation in terms of a composite clinical end point (death, stroke, reinfarction, need for emergency revascularization with angioplasty or bypass surgery, or recurrent ischemia): 13% versus 24%,P<.04.ConclusionsThis randomized trial showed that careful use of prophylactic aortic counterpulsation can prevent reocclusion of the infarct-related artery and improve overall clinical outcome in patients undergoing acute cardiac catheterization during myocardial infarction.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundIt has been shown that successful reperfusion of the infarct-related artery by thrombolysis can prevent left ventricular dilation after acute myocardial infarction; these beneficial effects were detected from several days to several months after infarction. To date, however, no study has shown that these effects can be demonstrated within hours after the onset of infarction. Furthermore, data are scarce on the independent impact of thrombolytic therapy and late vessel patency on ventricular volume and function. The aim of this study was to assess separate effects of thrombolysis and patency of the infarct-related artery on left ventricular size and function by serial two-dimensional echocardiographic examinations.Methods and ResultsWe evaluated 131 consecutive patients with first acute myocardial infarction by two-dimensional echocardiography in the following sequence: days 1, 2, 3, 7, and after 3 and 6 weeks. Intravenous streptokinase was administered in 81 patients, and 50 patients were treated without thrombolysis. Left ventricular end-diastolic volume, end-systolic volume, and ejection fraction were determined from apical two-and four-chamber views using the Simpson biplane formula and normalized to body surface area. Coro-nary angiography was performed in 107 patients after a mean of 26.0±20.2 (mean±SD) days after infarction. Patency of the infarct-related artery was assessed using TIMI criteria, with 54 considered patent (TIMI 3) and 53 with TIMI grade <3. On day 1, end-systolic volume was significantly higher in patients not receiving thrombolysis (37.7±15.3 versus 33.0±10.6 mL/ mi2,P=.045). End-systolic volume (ESVi) was significantly higher in patients treated without thrombolysis throughout the study, whereas significant differences in end-diastolic volume (EDVi) were detected from day 3 (P=.041) onward and in ejection fraction (EF) from day 2 (P=.025) onward, all differences becoming progressively more significant with time (6- week values: EDVi, 78.8±25.4 versus 65.9±15.7 mL/m2,P=.001; ESVi, 45.4±22.6 versus 33.9±15.1 mL/m2,P=.002; EF, 45.1±11.6% versus 50.2±10.1%,P=.018). Patients with an occluded infarct-related artery (TIMI <3) demonstrated highly significant differences at 6 weeks compared with patients with patent vessels (EDVi, 76.8±24.7 versus 65.2±15.6 mL/m2,P=.006; ESVi, 44.6±23.3 versus 31.9±12.2mL/m2,P=.001; EF, 45.0±11.6% versus 52.1±9.0%,P<.001), but these differences developed more slowly than that seen among the thrombolytic subgroups. Indeed, multivariate analysis demonstrated that thrombolysis was the major determinant of initial volumes (P=.08,.02, and.08 for EDVi, ESVi, and EF, respectively), while vessel patency was the overwhelming determinant of subsequent changes (P=.0033,.0002, and.0024 for EDVi, ESVi, and EF, respectively). Additionally, ventricular volumes were significantly higher and ejection fractions lower in patients with anterior versus inferior infarction, but even adjusting for these differences as well as those associated with age, sex, and initial ventricular volume, the additive and independent impact of thrombolysis and infarct vessel patency persisted.ConclusionsThese data indicate that the beneficial effect of thrombolysis on left ventricular size and function can be demonstrated in the earliest phases of acute myocardial infarction and that subsequent changes are mediated primarily through patency of the infarct-related artery. Thrombolytic therapy and late vessel patency thus have an additive and complementary impact in reducing ventricular dilation after myocardial infarction.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe objective of this study was to compare coronary flow reserve (CFR) as a measure of vascular integrity in asymptomatic middle-aged men with family history of coronary artery disease (CAD) and a high-risk lipid profile with men without risk factors for CAD using positron emission tomography (PET). Previous studies suggested that the assessment of CFR is a sensitive means to detect vascular abnormalities before angiographic appearance of CAD. N-13 ammonia PET scanning allows noninvasive evaluation of regional and global myocardial blood flow and thereby quantification of CFR.Methods and ResultsWe used dynamic N-13 ammonia PET imaging in conjunction with intravenous adenosine to assess regional and global CFR in asymptomatic middle-aged men with high risk (group 1, n=16) and men without any known risk factors (group 2, n= 11) for CAD. Group 1 patients were selected based on positive family history of CAD, one or more lipid abnormalities, and a normal stress test. No patient had history of diabetes or hypertension. A three-compartment tracer kinetic model developed and validated in our institution was used to calculate myocardial blood flow. Absolute myocardial blood flow (mL/100 g per minute) was calculated in five territories for each patient. CFR was defined as the ratio of blood flow during maximum pharmacological vasodilatation to blood flow at rest. Comparisons of CFR between the two groups of patients were performed. The mean age was similar between groups (group 1, 49.3±0.5 years; group 2, 48.1±8.7 years;P=NS). Group 1 had higher total cholesterol (mg/dL) (241±43 versus 173±34,P<.001), total cholesterol to high-density lipoprotein cholesterol ratio (6.4±1.6 versus 4.1±1.4,P<.001), and low-density lipoprotein cholesterol (mg/dL) (167±33 versus 107±32). No group 1 patient had evidence of ischemia by exercise ECG or exercise or pharmacological radionuclide perfusion studies. The mean global absolute myocardial blood flow at rest was not significantly different among groups (group 1, 76±18; group 2, 66±8;P=NS; (in mL/100 g per minute). However, blood flow after adenosine infusion was higher for group 2 (group 1, 217±56; group 2, 264±39;P<.001), which resulted in a larger CFR for group 2 (group 1, 2.93±0.86; group 2, 4.27±0.52;P<.001). Univariate linear regression analysis revealed significant negative correlation of CFR to total cholesterol (P<.05,r=−.41), low-density lipoprotein (P<.05,r= −.38), and total cholesterol to high-density lipoprotein cholesterol ratio (P<.05,r= −.47).ConclusionsNoninvasive quantification of absolute myocardial blood flow by N-13 ammonia PET allows the detection of abnormal vasodilatory response to intravenous adenosine in male patients with family history of CAD and high-risk lipid profiles. Early assessment of alterations of vascular reactivity to adenosine in relation to high-risk lipid profiles in asymptomatic men may allow early detection of preclinical atherosclerosis and may initiate modification and/or elimination of risk factors that may slow, retard, or even reverse the progression of CAD.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

In a randomized open study, the combination of either prostaglandin E1(PGE1) or pentoxifylline with controlled vascular training was compared with vascular training alone in patients with peripheral arterial occlusive disease in stage IIb. Forty-four patients were randomly assigned to treatment either of intensive vascular training alone (n=15) or in combination with either IV pentoxifylline (200 mg over 2 hours BID, n= 15) or PGE, (40 μg over 2 hours BID, n= 14). The basic therapy was a well-defined routine for vascular training, which was identical for all groups. The duration of therapy was 4 weeks. In all three test groups, there was a significant increase in the walking distance. There was a 119% increase in symptom-free walking distance in the exercise-only group. In comparison with exercise alone, the additional administration of pentoxifylline produced no greater effect; the increase was 105%. In contrast, administration of PGE, combined with exercise achieved a remarkable improvement of 604%. Between-group comparison revealed the significant superiority of treatment with PGE1 (P<.05). During the 1-year follow-up, there was a reduction in the walking performance in all groups, albeit of variable extent. In the exercise-only and the pentoxifylline groups, the maintained increase in walking distance was only 30% compared with baseline values before the beginning of therapy. In the PGE1group, on the other hand, the maintained improvement was 149%. Nine of 14 patients were still in stage IIa of peripheral arterial occlusive disease 1 year after PGE1therapy.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe present study was performed to evaluate the effects of nitroglycerin (GTN) on plasma arteriovenous cGMP production and to compare its hemodynamic effects in patients with congestive heart failure (CHF). We also estimated the potential clinical value of plasma arteriovenous cGMP production as an indicator of nitrate tolerance.Methods and ResultsPlasma arterial and venous cGMP levels, atrial natriuretic peptide level, and hemodynamic parameters were measured before and after GTN infusion in 14 patients with CHF. Although the plasma levels of arterial cGMP and atrial natriuretic peptide decreased immediately after GTN, the plasma level of venous cGMP did not change. GTN infusion caused a dose-dependent increase in plasma arteriovenous cGMP production, and there was a positive correlation between the decrease of pulmonary capillary wedge pressure and the increase of plasma arteriovenous cGMP production immediately after GTN. Hemodynamic tolerance was observed after both 12 and 24 hours, when plasma arteriovenous GMP production was also attenuated.ConclusionsThese findings indicate that the plasma arteriovenous cGMP difference is a clinical indicator of vasodilatory action of GTN and a useful indicator of nitrate tolerance in patients with CHF.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundLeft ventricular dysfunction is a frequent cause of death after successful surgical repair of mitral regurgitation. The role of preoperative echocardiographic left ventricular variables in the prediction of postoperative survival and thus their clinical implications remain uncertain.Methods and ResultsThe survival of 409 patients operated on between 1980 and 1989 for pure, isolated, organic mitral regurgitation and with a preoperative echocardiogram (within 6 months of operation) was analyzed. The overall survival was 75% at 5 years (90% of expected), 58% at 10 years (88% of expected), and 44% at 12 years (73% of expected). Operative mortality was 6.6% and markedly improved from 1980 to 1984 (10.7%) to 1985 to 1989 (3.7%). Multivariate analysis showed that age (P=.0003), date of operation (P=.003), and functional class (P=.016) but not left ventricular function were predictors of operative mortality. In the most recent period (1985 to 1989), operative mortality was 12.3% in patients age 75 years or older and 1.1% in patients younger than 75 years. Late survival was analyzed in the operative survivors. Multivariate analysis showed that the most powerful predictor was echocardiographic ejection fraction (EF) (P=.0004), followed by age (P=.0031), creatinine level (P=.0062), systolic blood pressure (P=.0164), and presence of coronary artery disease (P=.0237). The late survival at 10 years was 32±12% for patients with EF <50%, 53±9% for EF 50% to 60%, and 72±4% for EF ≤60%. The hazard ratio compared with EF.60% was 2.79 (95% confidence interval, 1.65 to 4.72) for EF ≤50% and 1.81 (95% confidence interval, 1.11 to 2.95) for EF 50% to 60%. Echocardiographic EF remained the best predictor of late survival, even when combined with left ventricular angiographic variables. The survival of patients with EF >60% was 100% of expected at 10 years but was better in patients in class I or II than in those in class III or IV (82±6% versus 59±6%, respectively, at 10 years;P=.0021). The preoperative predictors of operative and late mortality remained significant independent of the type of surgical correction performed in combined multivariate analyses.ConclusionsIn organic mitral regurgitation, (1) operative mortality has markedly decreased recently, being at a low 1.1% in patients younger than 75 years, and is predicted by age and symptoms and not by left ventricular function, and (2) left ventricular EF measured by echocardiography is the most powerful predictor of late survival. These results suggest that surgical treatment should be considered early, even in the absence of severe symptoms, in patients with severe mitral regurgitation, before left ventricular dysfunction occurs.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundSympathetic hyperactivity and parasympathetic withdrawal in patients with congestive heart failure correlate closely with disease severity and overall survival. The modulating effects of drugs on the autonomic dysfunction may contribute to improve survival. Low-dose scopolamine has a vagomimetic effect in normal subjects and patients after acute myocardial infarction. We assessed whether transdermal scopolamine would increase vagal activity in patients with congestive heart failure.Methods and ResultsHeart rate variability was assessed at baseline, 24 hours after one patch of transdermal scopolamine, and 48 hours after scopolamine withdrawal in 21 patients with moderate to severe heart failure. Scopolamine increased both time- and frequency-domain parameters of heart rate variability. Specifically, the mean RR interval and its SD increased by 5.5% (P<.001) and 45% (P<.001), respectively. The change remained significant when corrected for mean heart rate with a 39% (P<.01) increase of the coefficient of variation. The absolute power of the high-frequency component was also significantly augmented. All the parameters returned to base-line after scopolamine withdrawal. Individual analysis showed that in the 7 patients in whom scopolamine did not increase mean RR interval, heart rate variability did not change.ConclusionsTransdermal scopolamine increases vagal activity as assessed by heart rate variability in patients with congestive heart failure. This autonomic modulation does not occur in all patients and can be predicted by RR interval changes. Whether such restoration of the autonomic balance might have beneficial effects in the long-term management of patients with congestive heart failure remains to be determined.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundNonrheumatic stenosis of trileaflet aortic valves, often termed senile or calcific valvular aortic stenosis, is considered a “degenerative” process, but little is known about the cellular or molecular factors that mediate its development.Methods and ResultsTo characterize the developing aortic valvular lesion, we performed histological and immunohisto-chemical studies on Formalin-fixed and methanol-Carnoy's-fixed parafflin-embedded aortic valve leaflets or on frozen sections obtained at autopsy from 27 adults (age, 46 to 82 years) with normal leaflets (n=6), mild macroscopic leaflet thickening (n= 15), or clinical aortic stenosis (n=6). Focal areas of thickening (“early lesions”) were characterized by (1) subendothelial thickening on the aortic side of the leaflet, between the basement membrane (PAS-positive) and elastic lamina (Verhoeff–van Gieson), (2) the presence of large amounts of intracellular and extracellular neutral lipids (oil red O) and fine, stippled mineralization (von Kossa), and (3) disruption of the basement membrane overlying the lesion. Regions of the fibrosa adjacent to these lesions were characterized by thickening and by protein, lipid, and calcium accumulation. Control valves showed none of these abnormalities. Immunohistochemical studies were performed using monoclonal antibodies directed against macrophages (anti-CD68 or HAM-56), and contractile proteins of smooth muscle cells or myofibroblasts (anti-α-actin and HHF-35) or rabbit polyclonal antiserum against T lymphocytes (anti-CD3). In normal valves, scattered macrophages were present in the fibrosa and ventricularis, and occasional muscle actin-positive cells were detected in the proximal portion of the ventricularis near the leaflet base, but no T lymphocytes were found. In contrast, early lesions were characterized by the presence of an inflammatory infiltrate composed of non-foam cell and foam cell macrophages, occasional T cells, and rare α-actin-positive cells. In stenotic aortic valves, a similar but more advanced lesion was seen.ConclusionsThe early lesion of “degenerative” aortic stenosis is an active inflammatory process with some similarities (lipid deposition, macrophage and T-cell infiltration, and basement membrane disruption) and some dissimilarities (presence of prominent mineralization and small numbers of smooth muscle cells) to atherosclerosis.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundIn hypertrophic cardiomyopathy, ejection fraction is normal or increased, and force-length relations are reduced. However, three-dimensional (3D) motion and deformation in vivo have not been assessed in this condition. We have reconstructed the 3D motion of the left ventricle (LV) during systole in 7 patients with hypertrophic cardiomyopathy (HCM) and 12 normal volunteers by use of magnetic resonance tagging.Methods and ResultsTransmural tagging stripes were automatically tracked to subpixel resolution with an active contour model. A 3D finite-element model was used to interpolate displacement information between short- and long-axis slices and register data on a regional basis. Displacement and strain data were averaged into septal, posterior, lateral, and anterior regions at basal, midventricular, and apical levels. Radial motion (toward the central long axis) decreased slightly in patients with HCM, whereas longitudinal displacement (parallel to the long axis) of the base toward the apex was markedly reduced: 7.5±2.5mm (SD) versus 12.5±2.0 mm,P<.001. Circumferential and longitudinal shortening were both reduced in the septum (P<.01 at all levels). The principal strain associated with 3D maximal contraction was slightly depressed in many regions, significantly in the basal septum (−0.18±0.05 versus −0.22±0.02,P<.05) and anterior (−0.20±0.05 versus −0.23±0.02,P<.05) walls. In contrast, LV torsion (twist of the apex about the long axis relative to the base) was greater in HCM patients (19.9±2.4° versus 14.6±2.7°,P<.01).ConclusionsHCM patients had reduced 3D myocardial shortening on a regional basis; however, LV torsion was increased.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID