摘要:

Background—Platelet glycoprotein IIb/IIIa receptor blockade not only enhances epicardial flow but also improves microvascular perfusion. Inhibition of abnormal platelet–endothelial interactions may contribute to this beneficial effect. The present study was designed to determine whether glycoprotein IIb/IIIa receptor blockade influences endothelial vasomotor function and NO bioactivity in patients with coronary artery disease.Methods and Results—Forty patients with symptomatic coronary artery stenosis were studied before planned percutaneous coronary intervention. By using venous occlusion plethysmography, endothelium-dependent and -independent vasodilation was determined by measuring forearm blood flow responses to acetylcholine with and withoutNG-monomethyl-l-arginine (L-NMMA) and sodium nitroprusside. Vascular function tests were repeated during glycoprotein IIb/IIIa receptor blockade by tirofiban in 27 patients and by eptifibatide in 13 patients. A subgroup of 10 patients was retested 6 hours after stopping infusion of tirofiban. Glycoprotein IIb/IIIa receptor blockade by both substances improved acetylcholine-induced vasodilation and L-NMMA responses. Six hours after withdrawal of tirofiban infusion, the beneficial effects were not evident. Sodium nitroprusside–induced vasodilation was not changed by glycoprotein IIb/IIIa receptor blockade.Conclusions—These findings support the concept that abnormal platelet-endothelial interactions contribute to endothelial dysfunction and impaired NO bioactivity in patients with symptomatic coronary artery disease.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Aspirin inhibits platelet activation and reduces atherothrombotic complications in patients at risk of myocardial infarction and stroke. However, a sufficient inhibition of platelet function by aspirin is not always achieved. The causes of this aspirin resistance are unknown.Methods and Results—Patients undergoing coronary artery bypass grafting (CABG) have a high incidence of aspirin resistance. To evaluate functional and biochemical responses to aspirin, platelet-rich plasma was obtained before and at days 1, 5, and 10 after CABG. Thromboxane formation, aggregation, and &agr;-granule secretion were effectively inhibited by 30 or 100 &mgr;mol/L aspirin in vitro before CABG, but this inhibition was prevented or attenuated after CABG. Whereas the inhibition of thromboxane formation and aggregation by aspirin in vitro partly recovered at day 10 after CABG, oral aspirin (100 mg/d) remained ineffective. The inducible isoform of cyclooxygenase in platelets, COX-2, has been suggested to confer aspirin resistance. In fact, immunoreactive COX-2 was increased 16-fold in platelets at day 5 after CABG, but the COX-2 selective inhibitor celecoxib did not alter aspirin-resistant thromboxane formation. By contrast, the combined inhibitor of thromboxane synthase and thromboxane receptor antagonist terbogrel equally prevented thromboxane formation of platelets obtained before (control) and after CABG.Conclusions—Platelet aspirin resistance involves an impairment of both in vivo and in vitro inhibition of platelet functions and is probably due to a disturbed inhibition of platelet COX-1 by aspirin.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—The high rate of periprocedural complications resulting from atherothrombotic embolization after percutaneous intervention in diseased saphenous vein grafts is reduced by distal microcirculatory protection using a balloon occlusion and aspiration system. Whether filter-based catheters, which offer the inherent advantages of maintained perfusion and ease of use, are as effective for this purpose has not been established.Methods and Results—A total of 651 patients undergoing percutaneous intervention of 682 saphenous vein graft lesions were prospectively randomized to distal protection with the filter-based FilterWire EX versus the GuardWire balloon occlusion and aspiration system. Device success was 95.5% and 97.2% with the FilterWire EX and GuardWire, respectively (P=0.25). Postprocedural measures of epicardial flow and angiographic complications were similar between the 2 groups, although bailout IIb/IIIa inhibitors were required slightly less frequently in the FilterWire EX group (0% versus 1.5%,P=0.03). The primary end point, the composite incidence of death, myocardial infarction, or target vessel revascularization at 30 days, occurred in 9.9% of FilterWire EX patients and 11.6% of GuardWire patients (difference [95% CI]=−1.7% [−6.4%, 3.1%];Pfor superiority=0.53,Pfor noninferiority=0.0008).Conclusions—Distal protection with the FilterWire EX may be safely used as an adjunct to percutaneous intervention of diseased saphenous vein grafts and, compared with distal protection with the GuardWire balloon occlusion and aspiration system, results in similar rates of major adverse cardiac events at 30 days.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—The effects of exercise training (ET) on left ventricular (LV) remodeling in chronic heart failure are not definitively established, and the safety of ET in these patients is still debated.Methods and Results—This multicenter study investigated the long-term effect of moderate ET on LV remodeling, work capacity, and quality of life (QoL) in 90 patients with stable chronic heart failure caused by LV systolic dysfunction, randomized to a 6-month ET program (T, n=45) or a control group (C, n=45). All patients underwent resting echocardiography, a cardiopulmonary exercise test, 6-minute walking test, and QoL assessment at entry and after 6 months. At entry, end-diastolic (EDV) and end-systolic (ESV) volume, ejection fraction, work capacity, peak &OV0312;o2, and walking distance were similar in the 2 groups. After 6 months, LV volumes diminished in T (EDV, from 142±26 to 135±26 mL/m2,P<0.006; ESV, from 107±24 to 97±24 mL/m2,P<0.05) but increased in C (EDV, from 147±41 to 156±42 mL/m2,P<0.01; ESV, from 110±34 to 118±34 mL/m2,P<0.01). Ejection fraction improved in T (P<0.001) but was unchanged in C (P=NS). Significant improvement in work capacity (P<0.001), peak &OV0312;o2(P<0.006), walking distance (P<0.001), and QoL (P<0.01) was observed in T but not in C (P=NS). T showed a trend toward fewer (P=0.05) hospital readmissions for worsening dyspnea in the absence of other adverse cardiac events.Conclusions—In stable chronic heart failure, long-term moderate ET has no detrimental effect on LV volumes and function; rather, it attenuates abnormal remodeling. Furthermore, ET is safe and effective in improving exercise tolerance and QoL.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Left ventricular (LV) hypertrophy is an independent risk factor for cardiovascular morbidity and mortality in hypertensive subjects. Sympathetic activation has been suggested to contribute to LV hypertrophy, but this has not yet been conclusively validated in humans.Methods and Results—We comprehensively assessed total systemic and regional sympathetic activity by radiotracer dilution methods and microneurography in 15 untreated hypertensive subjects with echocardiographic evidence of LV hypertrophy (EH+), 11 hypertensive subjects with similar blood pressure but without LV hypertrophy (EH−), and 10 age-matched normotensive control subjects (NT). LV mass index was 87±15 g/m2in NT, 106±11g/m2in EH−, and 138±17g/m2in EH+ (P<0.001). Total body and renal norepinephrine spillover were higher in both hypertensive groups compared with NT (total norepinephrine spillover, NT 223±145 versus EH− 418±135 versus EH+ 497±303 ng/min; renal norepinephrine spillover, NT 38.8±25.3 versus EH− 88.6±58.0 versus EH+ 103.4±56.2 ng/min; bothP<0.05). However, muscle sympathetic nerve activity (NT 25±6 versus EH− 38±20 versus EH+ 57±19 bursts per 100 heartbeats;P<0.01) and cardiac norepinephrine spillover (NT 11.7±6.2 versus EH− 13.1±7.2 versus EH+ 28.6±17.4 ng/min;P<0.01) were only increased in EH+. Cardiac norepinephrine spillover correlated positively with LV mass index in all subjects (r=0.52;P<0.001).Conclusions—Our findings demonstrate that hypertensive LV hypertrophy is associated with increased sympathetic activity largely confined to the heart, suggesting that increased cardiac norepinephrine release is related to the development of LV hypertrophy.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Low birth weight may be associated with high blood pressure in later life through genetic factors, an association that may be explained by alterations in sympathetic and parasympathetic activity. We examined the association of birth weight with cardiac pre-ejection period and respiratory sinus arrhythmia (indicators of cardiac sympathetic and parasympathetic activity, respectively) and with blood pressure in 53 dizygotic and 61 monozygotic adolescent twin pairs.Methods and Results—Birth weight of the twins was obtained from the mothers. Pre-ejection period and respiratory sinus arrhythmia were measured with electrocardiography and impedance cardiography at rest, during a reaction time task, and during a mental arithmetic task. In the overall sample, lower birth weight was significantly associated with shorter pre-ejection period at rest, during the reaction time task, and during the mental arithmetic task (P=0.0001,P<0.0001, andP=0.0001, respectively) and with larger pre-ejection period reactivity to the stress tasks (P=0.02 andP=0.06, respectively). In within-pair analyses, differences in birth weight were associated with differences in pre-ejection period at rest and during both stress tasks in dizygotic twin pairs (P=0.01,P=0.06, andP=0.2, respectively) but not in monozygotic twin pairs (P=0.9,P=1.0, andP=0.5, respectively). Shorter pre-ejection period explained approximately 63% to 84% of the birth weight and blood pressure relation.Conclusions—Low birth weight is associated with increased sympathetic activity, and this explains a large part of the association between birth weight and blood pressure. In addition, our findings suggest that the association between birth weight and sympathetic activity depends on genetic factors.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—A family history of coronary heart disease (CHD) is an independent risk factor for cardiovascular events. However, the mechanisms underlying this susceptibility have not been fully elucidated. We hypothesized that an important mediator of the familial predisposition to CHD is subclinical atherosclerosis, which is detectable by noninvasive imaging.Methods and Results—We studied 1662 subjects (mean age 57, 51% women) in the Framingham Offspring Study who underwent carotid ultrasonography and had both biological parents in the original (parental) cohort. Parental CHD events were validated prospectively by a physician endpoint committee. The associations of carotid intima-media thickness (IMT) with premature parental CHD (occurring before age 60) and any parental CHD (no age restriction) were examined in age- and multivariable-adjusted analyses. Age-adjusted mean internal carotid IMT was higher in subjects who had at least one parent with premature CHD than in those without a validated parental history of premature CHD (men 1.13 versus 1.04 mm,P<0.01; women 0.92 versus 0.85 mm,P=0.03). In both sexes, these differences remained significant after adjustment for cardiovascular risk factors. In analyses without a restriction on parental age of CHD onset, the association between carotid IMT and parental CHD was not statistically significant. There was also no significant association of common carotid IMT with premature or any parental CHD.Conclusions—These findings suggest that subclinical atherosclerosis, assessed in the carotid arteries, is more prevalent in individuals with a family history of CHD. Early-onset parental CHD, in particular, identifies offspring with a strong familial predisposition to atherosclerosis.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Cardiac troponin-T is a sensitive marker of myocardial damage. In a prospective study, the effect of 2 different pH strategies during cardiopulmonary bypass on ischemic myocardial injury and clinical outcome was measured in a pediatric population.Methods and Results—One hundred one patients (31 neonates 13.2±8.3 days and 70 children 34.5±44.1 months of age) undergoing open-heart surgery were selected to either &agr;-stat (n=51) or pH-stat (n=50) acid-based management protocol. Serum troponin-T levels were measured before and 30 minutes after bypass and then 4 and 24 hours postoperatively. Surgical procedure, bypass details, inotropic support requirement, and postoperative recovery were recorded. Baseline troponin-T level was higher in neonates than in children (0.18±0.22 versus 0.04±0.05 &mgr;g/L,P=0.02). Also, a higher baseline level was found in patients with pulmonary hypertension (0.13±0.21 versus 0.04±0.05 &mgr;g/L,P=0.04). Cyanotic children showed a higher peak troponin-T level (3.76±3.11 versus 1.67±1.33 &mgr;g/L,P=0.04). Peak troponin levels showed a correlation with the length of circulatory arrest and aortic cross-clamp time. Postoperative levels remained high at 24 hours in patients requiring inotropic support. Peak troponin-T levels were significantly lower in the pH-stat group in patients with pulmonary hypertension (P=0.03) and in cases where circulatory arrest (P=0.01) or inotropic support (P=0.01) was necessary during operation than in those with &agr;-stat technique. Postoperative ventilation time and length of intensive care unit stay were also significantly longer with &agr;-stat than with pH-stat technique (P=0.005 andP=0.006, respectively).Conclusions—Cardiac troponin-T sensitively reflects myocardial damage in children. Our results suggest that pH-stat acid-based management protocol may provide better protection against ischemic myocardial damage than &agr;-stat technique.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Aortic intramural hematoma (IMH) evolves very dynamically in the short-term to regression, dissection, or aortic rupture. The aim of the present study was to assess the long-term clinical and morphological evolution of medically treated IMH.Methods and Results—Fifty of 68 consecutive patients with aortic IMH monitored clinically and by imaging techniques at 3, 6, and 12 months and annually thereafter were prospectively studied. Mean follow-up was 45±31 months. In the first 6 months, total IMH regression was observed in 14 and progression to aortic dissection in 18 patients; in 14 of these, the dissection was localized, and 12 later developed pseudoaneurysm. At the end of follow-up, the IMH had regressed completely without dilatation in 17 patients (34%), progressed to classical dissection in 6 (12%), evolved to fusiform aneurysm in 11 (22%), evolved to saccular aneurysm in 4 (8%), and evolved to pseudoaneurysm in 12 (24%). Evolution to dissection was related to echolucency (P<0.02) and to longitudinal extension of IMH (P<0.01). Multivariate analysis showed an independent association between regression and smaller maximum aortic diameter and between aneurysm formation and atherosclerotic ulcerated plaque and absence of echolucent areas in IMH.Conclusions—The most frequent long-term evolution of IMH is to aortic aneurysm or pseudoaneurysm. Complete regression without changes in aorta size is observed in one third of cases, and progression to classical dissection is less common. A normal aortic diameter in the acute phase is the best predictor of IMH regression without complications, and absence of echolucent areas and atherosclerotic ulcerated plaque are associated with evolution to aortic aneurysm.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Segmental ostial ablation of the pulmonary veins (PVs) allows for successful control of paroxysmal atrial fibrillation in many patients. We hypothesized that mapping of the left atrial-PV junction with a 64-electrode basket catheter would allow characterization of conduction patterns that would identify sites where ablation is required to electrically isolate the PV.Methods and Results—A 64-electrode basket catheter was used to map the PVs of 50 patients undergoing PV isolation procedures for the treatment of atrial fibrillation. Activation along each spline was classified as reflecting either longitudinal, transverse, or no activation. A longitudinal activation pattern recorded along a spline during sinus rhythm in right-sided PV and during CS pacing in left-sided PV before the delivery of any RF energy application had a sensitivity and specificity for a required ostial ablation site of 83% and 82%, respectively. When longitudinal activation along the spline was present during preablation recordings in both sinus rhythm and CS pacing, the sensitivity and specificity were 92% and 90%, respectively. A longitudinal activation pattern after the first RF application that produced a change in PV activation sequence had a sensitivity and specificity for sites where further ablation was required of 91% and 94%, respectively.Conclusions—Mapping of PV activation with a 64-electrode basket catheter allows characterization of conduction patterns that predict requirement for ablation. The presence of a longitudinal activation pattern is a strong predictor of ostial sites where ablative energy is required to electrically isolate the PV.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID