ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Apoptosis has been recognized in normal, including rapidly proliferating, cell populations and is inferred to be potentially responsible for the maintenance of stable cell numbers in tissues with various degrees of proliferative activity. Previous studies performed in rats indicated that despite the persistence of a relatively high level of injury-induced proliferative activity, total arterial smooth muscle content at 12 weeks remained unchanged from that measured at 2 weeks, suggesting that accrual of vascular smooth muscle cells is mitigated by cell death. The extent to which apoptosis may be observed in human atherosclerosis and/or restenosis, however, has not been previously established.Methods and Results We performed immunohistochemical studies on 56 specimens retrieved from patients undergoing directional atherectomy for primary atherosclerotic lesions or recurrent arterial narrowing after percutaneous revascularization (restenosis). Immunohistochemical staining disclosed evidence of apoptosis in 35 (63%) of the 56 specimens studied. When present, immunohistochemical evidence of apoptosis was typically limited to <2% of cells in the specimen. The finding of apoptosis, however, was not distributed equally among four groups of specimens studied. Specimens retrieved from patients with restenosis were more frequently observed to contain foci of apoptosis than specimens retrieved from patients with primary atherosclerotic lesions. Among 14 peripheral arterial specimens from patients with restenosis, 13 (93%) contained foci of apoptosis; in contrast, apoptosis was observed in only 6 (43%) of 14 peripheral specimens from patients with primary lesions (P=.0046). Among coronary arterial specimens, apoptosis was observed in 12 (86%) of 14 specimens from patients with restenosis versus 6 (29%) of 14 specimens from patients with primary obstructions (P<.0075).Conclusions Apoptosis is a feature of human vascular pathology, including restenotic lesions and, to a lesser extent, primary atherosclerotic lesions. The findings of the present study suggest that apoptosis may modulate the cellularity of lesions that produce human vascular obstruction, particularly those with evidence of more extensive proliferative activity. (Circulation. 1995;91:2703-2711.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Reperfusion following myocardial ischemia causes a rapid and transient release of inositol (1,4,5)triphosphate (Ins(1,4,5)P sub 3). The aim of this study was to test whether this increased Ins(1,4,5)P3release was important for the development of ventricular arrhythmias and whether agents that inhibit this signal transduction pathway, such as aminoglycoside antibiotics, suppress arrhythmias.Methods and Results In perfused rat hearts, ventricular tachycardia (VT), ventricular fibrillation (VF), and accumulation of Ins(1,4,5)P sub 3 were measured during early reperfusion. A number of different compounds, including neomycin, gentamicin, streptomycin, spermine, reserpine, and prazosin, were effective in inhibiting the reperfusion-induced Ins(1,4,5)P sub 3 release and the onset of VT and VF in parallel. A strong correlation existed between Ins(1,4,5)P3content, measured at 2 minutes of reperfusion, and the incidence of reperfusion VT and VF. In addition, intravenous gentamicin suppressed the onset of arrhythmias under ischemic and reperfusion conditions in vivo.Conclusions Our results are consistent with the view that Ins(1,4,5)P sub 3 release plays a pivotal role in mediating arrhythmias during early reperfusion. Agents inhibiting Ins(1,4,5)P3release are antiarrhythmic and may have potential use clinically. (Circulation. 1995;91:2712-2716.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Ventricular dilation, indexed by marked shifts toward larger volumes of the end-diastolic pressure-volume relation (EDPVR), has been considered to represent an irreversible aspect of ventricular remodeling in end-stage heart failure. However, we hypothesized that such dilation could be reversed with sufficient hemodynamic unloading, such as can be provided by a left ventricular assist device (LVAD).Methods and Results The EDPVRs of hearts from seven patients with end-stage idiopathic cardiomyopathy and comparable baseline hemodynamics were measured ex vivo at the time of cardiac transplantation; these were compared with EDPVRs from three normal human hearts that were technically unsuitable for transplantation. Four of the patients received optimal medical therapy; three of the patients, who deteriorated on optimal therapy, underwent LVAD support for (approximately) 4 months. Compared with the normal hearts, EDPVRs of hearts from medically treated patients were shifted toward markedly larger volumes. In contrast, EDPVRs of hearts from LVAD patients were similar to those of normal hearts.Conclusions Chronic hemodynamic unloading of sufficient magnitude and duration can result in reversal of chamber enlargement and normalization of cardiac structure as indexed by the EDPVR, both important aspects of remodeling, even in the most advanced stages of heart failure. (Circulation. 1995;91:2717-2720.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background It has been reported that the D allele of an insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene is associated with conditions of increased cardiovascular risk, including left ventricular hypertrophy.Methods and Results Considering that a genetically determined overactivity of the renin-angiotensin system may influence cardiac as well as vascular growth, we investigated possible relations between ACE I/D genotype and carotid artery wall thickness (B-mode ultrasound) in 199 subjects, 50 to 64 years old, sampled from the general population of Vobarno, a small town in northern Italy. ACE DD genotype was associated with significantly higher common carotid artery intima-media thickness (P=.003). The occurrence of carotid atherosclerotic plaques was similar in the different genotypes. There was no association of the ACE I/D genotype with blood pressure values (either casual or 24-hour ambulatory monitored).Conclusions ACE DD genotype may be considered a risk factor for the development of common carotid intima-media thickening in our study population. (Circulation. 1995;91:2721-2724.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Early restoration and maintenance of normal (TIMI 3) blood flow during acute myocardial infarction is critical for optimal preservation of left ventricular function and survival. Recombinant plasminogen activator (r-PA, reteplase) is a nonglycosylated deletion mutant of wild-type tissue-type plasminogen activator (TPA) that has been shown to achieve more rapid and complete thrombolysis compared with other plasminogen activators in animal models.Methods and Results The RAPID Trial was designed to test the hypothesis that bolus administration of one or more dosage regimens of r-PA was superior to standard-dose alteplase (TPA) in achieving infarct-related artery patency 90 minutes after initiation of treatment. Six hundred six patients with acute myocardial infarction were randomized to one of four treatment arms: (1) TPA 100 mg IV over 3 hours, (2) r-PA as a 15-MU single bolus, (3) r-PA as a 10-MU bolus followed by 5 MU 30 minutes later, or (4) r-PA as a 10-MU bolus followed by 10 MU 30 minutes later. Coronary arteriography was performed at 30, 60, and 90 minutes after initiation of treatment and at hospital discharge. The 10+10-MU r-PA group achieved better 90-minute and 5- to 14-day TIMI 3 flow (63% (CI, 55% to 71%) versus 49% (41% to 57%), P=.019, and 88% (82% to 94%) versus 71% (63% to 79%), P<.001, respectively) than the TPA group. The TIMI 3 flow in the 10+10-MU r-PA group at 60 minutes was equivalent to that in the TPA group at 90 minutes (51 versus 49%). Global ejection fraction and regional wall motion in the 10+10-MU r-PA group were superior to those of the TPA group at hospital discharge (53+-1.3% versus 49+-1.3%, P=.034; -2.19+-0.12 versus -2.61+-0.13 SD per chord, P=.02, respectively). The 15-MU and 10+5-MU r-PA patency and left ventricular function results were similar to those of the TPA and inferior to those of the 10+10-MU r-PA group. Bleeding complications were similar between the groups.Conclusions r-PA given as a double bolus of 10+10 MU achieves more rapid, complete, and sustained thrombolysis of the infarct-related artery than standard-dose TPA, without an apparent increased risk of complications. This was associated with improved global and regional left ventricular function at hospital discharge. (Circulation. 1995;91:2725-2732.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Successful reversal of abrupt vessel closure without resultant major ischemic complications (death, Q-wave myocardial infarction, or coronary artery bypass graft surgery) is achieved in nearly half of all cases of abrupt vessel closure. The long-term outcome of these patients has not been previously addressed, and it is not clear whether they have a different prognosis than that of patients who have a successful procedure not associated with transient vessel closure.Methods and Results We examined 4863 consecutive patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) or directional coronary atherectomy (DCA). Eighty-eight patients had an uncomplicated, successfully reversed transient in-laboratory vessel closure (group 2) and were compared with 4775 patients who had a successful procedure not associated with transient in-laboratory closure (group 1). Clinical follow-up was available in 4839 patients (99.5%), with a mean duration of 41+-23 months (range, 1 to 104 months). Survival analysis showed that successfully treated, uncomplicated transient vessel closure per se does not have an adverse effect on long-term prognosis (death, myocardial infarction, or coronary interventions). However, when the procedure (PTCA or DCA) was associated with an increase in creatine kinase-MB (CK-MB), there was a significant adverse effect on long-term outcome. By multivariate logistic regression, an increase in postprocedure CK-MB was the most significant correlate for cardiac death (risk ratio, 1.25; P<.0001). An increase in CK-MB was also the most important correlate for major ischemic complications (death, infarction, or coronary interventions) on follow-up (risk ratio, 1.08; P=.0005).Conclusions Transient, uncomplicated in-laboratory vessel closure per se does not have an adverse long-term effect. However, a concomitant elevation of postprocedure cardiac enzymes has an important and significant adverse effect on long-term outcome. This study suggests that periprocedural creatine kinase isoenzyme determination in patients experiencing in-laboratory coronary closure has important prognostic implications. (Circulation. 1995;91:2733-2741.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID