摘要:

BackgroundCigarette smoking has been associated with increased risk of atherosclerotic diseases in hospital–based studies and in studies of middle-aged populations but not in population-based studies of older adults with and without clinical cardiovascular disease.Methods and ResultsWe investigated the relation of smoking to carotid artery atherosclerotic disease, expressed as intimal-medial wall thickness and arterial lumen narrowing (stenosis) measured by ultrasound. Subjects were 5116 older adults participating in the baseline examination of the Cardiovascular Health Study, a community-based study of cardiovascular diseases in older age. With increased smoking there was significantly greater internal and common carotid wall thickening and internal carotid stenosis: current smokers > former smokers > never-smokers; for instance, the unadjusted percent stenosis was 24%, 20%, and 16%, respectively (P< .0001). A significant dose-response relation was seen with pack-years of smoking. These findings persisted after adjusting for other cardiovascular risk factors and were also confirmed when analyses were restricted to those without prevalent cardiovascular disease. The difference in internal carotid wall thickness between current smokers and nonsmokers was greater than the difference associated with 10 years of age among never-smoking participants (0.39 mm versus 0.31 mm). Among all participants, the prevalence of clinically significant (≥ 50%) internal carotid stenosis increased from 4.4% in never-smokers to 7.3% in former smokers to 9.5% in current smokers (P< .0001).ConclusionsThese findings extend previous reports of a positive relation between smoking and carotid artery disease to a population-based sample of older adults using several different indicators of atherosclerotic disease.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThere is substantial evidence that a low serum level of HDL cholesterol (HDLC) is a risk factor for coronary deaths. However, data on older people are scarce, and previous studies have not examined this association in relation to alcohol intake.Methods and ResultsCoronary mortality, all-cause mortality, and mortality due to alcohol and violence were related to HDLC levels among 7052 male smokers 50 to 69 years old in south and west Finland enrolled from 1984 to 1988 in the ATBC (AT, alpha-tocopherol; BC, beta-carotene) Study placebo group. During the average follow-up period of 4.7 years, 620 men died; 222 of these deaths were from coronary heart disease and 82 from causes related alcohol and violence. HDLC levels were inversely associated with coronary mortality, irrespective of age, whereas high total cholesterol was positively associated with coronary mortality among the younger men, 50 to 59 years of age, but not among the older men, 60 to 69 years old. Correction for temporal variation in HDLC measurement indicated a 43% stronger inverse association between HDLC and coronary mortality compared with that based only on a single value. The inverse association of HDLC and coronary mortality was less marked at higher levels of alcohol intake. All-cause and alcohol- and violence-related mortality were positively associated with HDLC among the younger men. All-cause mortality showed a U-shaped dose response among men ≥ 60 years old.ConclusionsPrevious studies may have underestimated the beneficial effect of high HDLC because of regression-dilution bias and the confounding effect of heavy alcohol intake. This study supports the view that, particularly among older men, lipoprotein fractions may be more appropriate for screening than total cholesterol.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundExogenous adenosine has been shown to increase muscle sympathetic nerve activity (MSNA), blood pressure, heart rate, and ventilation in conscious humans, effects attributed to peripheral chemoreceptor activation.Methods and ResultsTo determine whether endogenous adenosine has similar effects and whether they are mediated through chemoreceptor activation, we examined the effects of dipyridamole, an inhibitor of adenosine reuptake, on sympathetic nerve activity and ventilation. Twenty studies were conducted on separate days in 15 healthy volunteers. We examined responses to dipyridamole 0.56 mg/kg during room air breathing (n = 7), during hyperoxia (100% O2, n = 6), and during room air breathing after pretreatment with aminophylline (n = 7). During room air breathing, dipyridamole increased MSNA from 231 ± 42 to 504 ± 136 U/min, heart rate from 65 ± 3.8 to 96 ± 4.7 beats per minute, and systolic blood pressure from 129 ± 3.5 to 140 ± 4.8 mm Hg; central venous pressure decreased from 5.5 ± 0.4 to 4.5 ± 0.3 mm Hg (P< .01), and minute ventilation increased from 7.8 ± 0.6 to 9.1 ± 0.5 L/min (P< .01). During peripheral chemoreceptor suppression (with hyperoxia), there was a dissociation of the effects of dipyridamole on ventilation and sympathoexcitation. Effects on ventilation were attenuated, but sympathoexcitatory effects were not. Pretreatment with aminophylline, an adenosine receptor antagonist, either abolished (blood pressure, minute ventilation, and end-tidal CO2) or markedly attenuated (MSNA and heart rate) the effects of dipyridamole during room air breathing.ConclusionsAugmentation of endogenous adenosine with dipyridamole increases sympathetic nerve activity and ventilation in conscious humans. The ventilatory effects of endogenous adenosine are mediated predominantly by chemoreceptor activation, but the sympathetic and hemodynamic responses to endogenous adenosine are probably mediated by an additional afferent mechanism that is independent of peripheral chemoreceptor activation.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundBecause pulmonary artery size is considered by most investigators to be a major prognosticator of outcome in patients undergoing staged Fontan reconstruction, the objective of the present study was to determine the efficacy of noninvasive measures in determining pulmonary artery size.Methods and ResultsThis study analyzed the T1-weighted, spin-echo magnetic resonance and echocardiographic images of 36 functional single-ventricle patients throughout stages of Fontan reconstruction (prebidirectional and postbidirectional cavopulmonary anastomosis and after Fontan) and compared them with angiography images at cardiac catheterization. Magnetic resonance imaging had a high degree of agreement with angiography, with the McGoon index agreeing better than the Nakata index and absolute right and left pulmonary diameters. Although echocardiography had fair agreement with angiography, it agreed less well and had a wider standard deviation than magnetic resonance imaging for all indexes and measurements and, based on the prediction interval, would be a poorer prospective measure of pulmonary artery size in this population. In addition, echocardiography was a poorer measure of pulmonary artery size as the size of the vessel increases. Magnetic resonance imaging correctly detected five of five patients with nonconfluent branch pulmonary arteries and six of six patients with stenoses, whereas echocardiography was unable to visualize any of the patients with nonconfluent branch pulmonary arteries with certainty and only two of six (33%) with stenoses.ConclusionsMagnetic resonance imaging is a useful, noninvasive tool to determine pulmonary artery size in patients undergoing Fontan reconstruction and is superior to echocardiography. Echocardiography was a fair predictor of pulmonary artery size, but magnetic resonance imaging agreed with angiography better than echocardiography and outperformed echocardiography in diagnosing branch pulmonary artery discontinuity and stenoses. Magnetic resonance imaging may avoid unnecessary cardiac catheterization, especially in older patients, and may obviate the need for jugular or subclavian catheterization in those who have undergone bidirectional cavopulmonary anastomosis.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe inability to obtain complete diagnoses with transthoracic echocardiography in many adults with congenital heart disease provided the incentive to evaluate prospectively the individual and combined roles of magnetic resonance imaging (MRI) and transesophageal echocardiography (TEE) as “second-line” techniques for unresolved diagnostic problems.Methods and ResultsEighty-five patients were studied; 81 had MRI with a 0.5-T magnet to obtain spin- echo images, cine-MRI, and flow-velocity maps. Seventy-nine patients had TEE (37 biplane). A simple score (range, 0 to 1) was used for quantification of the results of MRI and TEE alone, for their comparison (in the 75 patients who had both), and for assessment of their combination. MRI, TEE, or their combination achieved a score of at least 0.75 in 18 of 25 diagnostic categories. A summary of the scores showed that for intracardiac anatomy. MRI scored 0.34, TEE scored 0.71 (P< .0001), and MRI plus TEE scored 0.84 (P< .003); for extracardiac anatomy, MRI scored 0.76, TEE scored 0.23 (P< .0001), and MRI plus TEE scored 0.84 (P= NS); and for hemodynamics and function, MRI scored 0.58, TEE scored 0.41 (P< .05), and MRI plus TEE scored 0.67 (P= NS). Total scores were MRI, 0.52; TEE, 0.50 (P= NS); and MRI plus TEE, 0.80 (P< .0001). MRI and TEE were inadequate for collateral and coronary arteries and pulmonary vascular resistance. Cine-MRI and flow-velocity maps comprised 43% of the MRI scores. Biplane TEE was better than single plane (scores of 0.59 versus 0.42,P< .0001).ConclusionsMRI and TEE are important and complementary “second-line” investigations for congenital heart disease. Analysis of their performance in a wide range of diagnostic categories provides guidelines for their judicious application. Where both are available, diagnostic catheterizations are either obviated or simplified.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundWe investigated the plasma concentration of thromboxane B2(TXB2), a stable metabolite of thromboxane A2(TXA2), to assess platelet activation in 78 patients who had pulmonary hypertension associated with congenital heart disease (PH group) and 16 patients with almost normal hemodynamics (control group).Methods and ResultsThe PH group was divided into two subgroups: pulmonary vascular resistance (Rp) ≤ 10 U/m2(Rp≤ 10 group) and > 10 U/m2(Rp > 10 group). In addition, the Rp ≤ 10 group was divided on the basis of clinical symptoms into groups with dyspnea (dyspnea[+] group) and without dyspnea (dyspnea[-] group). Plasma TXB2levels were measured by radioimmunoassay. Plasma TXB2levels in the three groups (control, Rp ≤ 10, and Rp > 10) were significantly different (P< .005); the TXB2levels in the Rp ≤ 10 group were significantly higher than the others. Among the Rp ≤ 10 patients, the plasma TXB2levels were significantly higher in the dyspnea(+) group than in the dyspnea(−) group (P< .0001). In addition, the pulmonary-to-systemic flow ratio and pulmonary blood flow divided by body surface area were significantly higher in the dyspnea(+) group than in the dyspnea(-) group (P< .02 andP< .002, respectively).ConclusionsThese findings suggest that platelet activation led to increased TXA2release in patients with pulmonary hypertension, especially those with dyspnea and Rp ≤ 10. TXA2release from platelets probably caused constriction of the pulmonary arterioles and the bronchi, thus worsening pulmonary hypertension and dyspnea in these patients. In the patients with high Rp values, it was considered that the number of pulmonary arterioles where platelets could be activated had been reduced.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundRestenosis after catheter-based revascularization has been demonstrated to be primarily caused by medial and/or intimal smooth muscle cell (SMC) proliferation. The objective of this study was investigate the ability of local emission of β-particles from a32P- impregnated titanium “stent” wire source to inhibit vascular SMC and endothelial cell proliferation in cell culture and to determine the dose-response characteristics of this inhibition.Methods and ResultsA series of experiments were performed using 0.20-mm-diameter titanium wires that were impregnated with varying low concentrations of32P (activity range, 0.002 to 0.06 μCi/cm wire, n = 47) or31P (nonradioactive control, n = 28) in cultures of rat and human aortic SMCs and in cultured bovine aortic endothelial cells. The zone of complete cell growth inhibition (in millimeters from stent wire) was measured using light microscopy in the cultures exposed to the radioactive (32P) or control (31P) wires at 6 and 12 days after plating. In both rat and human SMC cultures there was a distinct 5.5- to 10.6-mm zone of complete SMC inhibition at wire activity levels ≥ 0.006 μCi/cm. In contrast, there was no zone of inhibition surrounding the control (31P impregnated) wires (P< .001 versus32P wires at all wire activities ≥ 0.006 μCi/cm for human and rat SMCs). Proliferating bovine endothelial cells were more radioresistant than SMCs, with no zone of inhibition observed at wire activity levels up to 0.019 μCi/cm (P< .001 versus SMCs at 0.006 μCi/cm and 0.019 μCi/cm).ConclusionsWe conclude that very low doses of β-particle emission from a32P-impregnated stent wire (activity levels as low as 0.006 μCi/cm of wire) completely inhibit the growth and migration of both rat and human SMCs within a range of 5.5 to 10.6 mm from the wire. Endothelial cells appear to be much more radioresistant than SMCs. These data suggest that an intra-arterial stent impregnated with a low concentration of32P may have a salutary effect on the restenosis process. Whether this approach can be used successfully and safely to inhibit restenosis in vivo and in the clinical setting is under investigation.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundReperfusion after prolonged coronary artery occlusion may be followed by additional myocardial necrosis persisting for hours to days. Potential mechanisms include neutrophil-mediated injury and compromised flow within the microcirculation of the reperfused myocardium. Poloxamer 188 is a nonionic surfactant with beneficial hemorheological and neutrophil-inhibitory properties. The purpose of the present study was to determine if poloxamer 188 is capable of reducing the myocardial injury associated with sustained reperfusion and to examine the effect of treatment duration.Methods and ResultsThree groups of closed-chest dogs underwent 90 minutes of left anterior descending coronary artery occlusion (angioplasty balloon) and 72 hours of reperfusion. Poloxamer 188, formulated as RheothRx Injection (Burroughs Wellcome Co), was given as a 75 mg/kg IV bolus 15 minutes before reperfusion followed by a 150 mg·kg−1·h−1continuous IV infusion for 4 hours (n = 13) or 48 hours (n = 13); control dogs (n = 12) received saline for 48 hours. The 48-hour infusion of poloxamer 188 resulted in a 42% reduction in infarct size (as a percent of the area at risk) compared with the control group (25.0 ± 4.2% versus 43.3 ± 4.3%,P≤ .01), whereas the 4-hour group demonstrated a 25% reduction in infarct size compared with the control group (32.4 ± 4.3%,P= .08). ANCOVA demonstrated that the 48-hour infusion of poloxamer 188 reduced myocardial infarct size independent of differences in collateral blood flow (P= .002 versus control). A trend toward infarct size reduction was observed in the 4-hour infusion group (P= .098 versus control by ANCOVA). Plasma creatine phosphokinase concentration was lower in both poloxamer 188-treated groups (P< .05 versus control). Global left ventricular ejection fraction at 72 hours of reperfusion was improved in the 48-hour infusion group compared with the control group (43 ± 3.1% versus 33 ± 2.0%,P< .05), whereas ejection fraction in the 4-hour group was 37 ± 1.3% (P= NS versus control). Regional ventricular function was also significantly better in the 48-hour infusion group compared with the control group. In vitro studies demonstrated that at concentrations comparable to those achieved in vivo, poloxamer 188 inhibited neutrophil chemotaxis. This finding may represent a beneficial mechanism of action.ConclusionsA 48-hour infusion of poloxamer 188 reduced myocardial infarct size and improved left ventricular function in this dog model of 90 minutes of coronary artery occlusion and 72 hours of reperfusion. The finding that the 4-hour infusion of poloxamer 188 did not result in similar benefits suggests that additional reperfusion injury occurred between 4 and 48 hours.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundPlatelets play an important role in the pathophysiology of acute coronary syndromes. The interaction between the platelet glycoprotein Ib receptor and von Willebrand factor is a critical event allowing platelet adhesion and aggregation and subsequent thrombus formation in vessels with high shear rates and damaged endothelium. Therefore, we tested the hypotheses that VCL, an antagonist of von Willebrand–glycoprotein Ib binding domain, (1) attenuates/abolishes cyclic flow variations in stenosed, endothelium-injured coronary arteries in nonhuman primates and (2) reduces botrocetin-induced platelet aggregation in vitro after intravenous in vivo administration.Methods and ResultsCyclic flow variations were established in anesthetized, open-chest baboons (n = 18). The baboons were divided into three groups. One group (n = 8) received a bolus of VCL (4 mg/kg IV) followed by an infusion (6 mg·kg−1·h−1) for 90 minutes (schedule A). Another group (n = 6) received a 2-mg/kg bolus followed by an infusion of 3 mg·kg−1·h−1for 90 minutes (schedule B). The third group received a placebo infusion of normal saline. Under dosing schedule A, cyclic flow variations were abolished in 7 of 8 baboons after 33 ± 18 minutes and markedly attenuated in 1. The frequency of cyclic flow variations fell from 18 ± 9.4 per hour during the control period to 1 ± 2.5 per hour after VCL infusion,P< .002. After cessation of infusion, cyclic flow variations remained abolished in 5 of 7 animals for > 3 hours and returned in 2 of 7 after 2 to 2.5 hours. Under schedule B, cyclic flow variations were abolished in 3 of 6 baboons and markedly reduced in the remainder. The number of cyclic flow variations fell from 17 ± 4.8 per hour during the control period to 5 ± 4.9 per hour after the VCL infusion,P< .001. The cyclic flow variations returned spontaneously at 38 ± 40 minutes under this dosing schedule. Placebo infusion of saline had no effect on cyclic flow frequency or severity. VCL administration was associated with slight prolongation in bleeding time and a reduction in botrocetin-induced platelet aggregation. The bleeding time increased from a control time of 88 ± 32 to 276 ± 204 seconds,P< .03, and from 142 ± 28 to 176 ± 36 seconds,P= .056, for schedules A and B, respectively. VCL decreased platelet aggregation in response to botrocetin (20 μg/mL), from a control value of 66 ± 30.3 to 33 ± 31.3 ω,P< .05, and from 64 ± 23.5 to 46 ± 15.8 ω,P= .006, for dosing schedules A and B, respectively.ConclusionsTherefore, administration of a peptide fragment corresponding to von Willebrand–glycoprotein Ib binding domain (1) is effective in abolishing cyclic flow variations in stenosed, endothelium-injured coronary arteries and (2) reduces platelet aggregation in vivo in response to botrocetin in nonhuman primates.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundIn humans, chronic ventricular tachycardia (VT) is usually associated with myocardial infarcts that involve the interventricular septum. In an effort to more closely mimic the anatomic substrate that gives rise to chronic VT in humans, we developed a canine model of VT in which the anterior septal coronary artery was ligated. The site of earliest activation, the subsequent activation sequence, and the mechanism of VT associated with the resultant ventricular septal infarct was then evaluated to determine if this model accurately reflected the characteristics of human VT.Methods and ResultsSeventeen dogs underwent occlusion-reperfusion ventricular septal infarcts. Four to 7 days later, electrophysiological studies were performed. VT was initiated by programmed electrical stimulation and terminated by pacing at a cycle length of 50% to 75% of the VT cycle length. Electrophysiological studies were performed using a 256-channel mapping system. A total of 15 VT morphologies were mapped in 9 animals. Fourteen of 15 morphologies had septal subendocardial sites of earliest activation and 1 had a septal midwall site of earliest activation. VT ablation was performed using a nitrous oxide cryoprobe and confirmed the site of earliest activation by subsequently rendering VT noninducible. Electrophysiological studies demonstrated four distinct VT activation sequences: (1) circular reentrant (n = 7), (2) concentric spread (n = 5), (3) figure-of-eight (n = 2), and (4) septal midwall (n = 1).ConclusionsThis canine model of ventricular septal infarction produces VTs with sites of earliest activation and activation sequences similar to those in humans. A reentrant mechanism as the basis of these arrhythmias is supported by the following observations: (1) all VT was initiated and terminated with programmed electrical stimulation; (2) VT activation sequences were consistent with reentry; and (3) precise interruption of the sequence terminated the VT and rendered it noninducible.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID