摘要:

Background The major morbidity of percutaneous transluminal coronary angioplasty is acute thrombosis and restenosis of the dilated lesion.Platelet-thrombus deposition occurs within minutes after injury, is primarily mediated by thrombin, causes acute occlusion, and contributes to late restenosis. Experimentally, specific thrombin inhibitors have prevented mural thrombosis. However, local therapy may be more effective than systemic treatment. We tested the hypothesis that high local concentrations of an antithrombin drug at the site of arterial injury following balloon angioplasty inhibit platelet thrombus formation equally or better than conventional systemic treatment and at lower systemic anticoagulant levels.Methods and Results Balloon angioplasty of the carotid arteries of 29 pigs was performed using systemic intravenous treatment with heparin (100 U/kg, groups I and II), suboptimal r-hirudin (0.3 mg/kg, group III), and higher-dose r-hirudin (0.7 mg/kg, group IV), which is the lowest dose that completely inhibited arterial thrombosis in the pig. Immediately after balloon angioplasty of the first carotid, additional local therapy with placebo (group I) or r-hirudin (groups II, III, and IV; 0.3 mg/kg in 1 mL) was administered with distal perfusion through a new percutaneous double-balloon catheter. After 1 hour of local drug delivery, angioplasty of the contralateral carotid was performed. Reflow for 1 hour was permitted to both carotids to compare the short-term effect of local plus systemic treatment with systemic treatment on quantitative Indium-111-labeled platelet deposition and macroscopic mural thrombus formation on deeply injured carotid segments. Local drug delivery of placebo compared with systemic heparin treatment resulted in no change of platelet deposition (x 106/cm2, mean+-SEM) in controls (group I, 91.0+-23.5 versus 80.8+-19.4), but local delivery of r-hirudin resulted in a significant reduction in group II (15+-2.5 versus 71.3+-14.5; P<.02) and group III (11.4+-2.5 versus 80.5+-11.4; P<.01) and was borderline in group IV (7.4+-1.8 versus 14.1+-7.4; P=.05), respectively. The incidence of macroscopic mural thrombus formation with local and systemic treatment was 86% and 75% in group I, 16% and 70% in group II, 14% and 71% in group III, and 0% and 16% in group IV, respectively.Conclusions Local therapy with the specific thrombin inhibitor r-hirudin significantly reduces short-term quantitative platelet deposition and macroscopic mural thrombus formation following balloon angioplasty compared with systemic treatment of conventional doses of heparin and hirudin and requires a significantly smaller amount of the recombinant drug. (Circulation. 1994;90:2474-2480.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Effects of systolic left ventricular pressure (LVP) on rates of pressure fall remain incompletely understood.This study analyzed phase-plane dP/dt versus LVP plots to differentiate between accelerating and decelerating effects and to investigate the variability in reported load effects on rates of LVP fall.Methods and Results Abrupt aortic occlusions were performed by inflating a balloon positioned in the ascending aorta of anesthetized open-chest dogs (n=17). The occlusions resulted in clamp elevations of systolic LVP. In protocol A, the elevations of systolic LVP induced by total aortic occlusions were timed at early, mid, and late ejection. The magnitude of the elevations was 36.0+-3.6 mm Hg for early, 11.6+-0.6 mm Hg for mid, and negligible for late occlusions. The course of LVP fall appeared to be more complex than previously appreciated. Pressure fall might be subdivided in an initial accelerative phase, an intermediate decelerative phase, and a terminal decelerative phase. The initial phase accelerated with mid and late occlusions. The intermediate phase slowed down with early and to a lesser extent with mid occlusions. The terminal phase was never affected by aortic clamp occlusions. In protocol B, early elevations of systolic LVP were obtained with multiple graded aortic occlusions. The effects of matched LVP elevations of 12 mm Hg on rate of LVP fall were evaluated with the time constant of LVP fall (tau) and showed an interanimal variability ranging from acceleration and a 20% decrease in tau to deceleration and a 35% increase in tau. Changes in tau were moderately correlated with commonly used indexes of contractility (peak +dP/dt, r=-.78; regional fractional shortening, r=-.63). These changes in tau showed a close correlation with the systolic LVP of the test beat, expressed as a percentage of the peak isovolumetric LVP, obtained with total aortic occlusion (r=.984). This suggested that the contraction-relaxation coupling should be analyzed in terms of peak force development rather than contraction velocity or ejection fraction.Conclusions LVP fall could be subdivided into an initial accelerative phase, an intermediate decelerative phase, and a terminal decelerative phase.Effects of elevations in systolic LVP on rate of LVP fall could be predicted by knowing peak isovolumetric LVP. Nonuniformity of LVP fall and adequate interpretation of load effects should be taken into account when clinical situations or pharmacological interventions are considered. In congestive heart failure, slow LVP fall could mainly reflect working conditions close to isovolumetric rather than relaxation disturbances. (Circulation. 1994;90:2481-2491.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background To determine the transmural pressure-dimension relations of the right atrium (RA) and right ventricle (RV) before and after pericardiectomy, six open-chest dogs were instrumented with pericardial balloons placed over the RA and RV free walls.Methods and Results RA appendage dimensions and RV free-wall segment lengths were measured using sonomicrometry. Intact-pericardium RA and RV transmural pressures were calculated by subtracting the pericardial pressures (measured using balloons) from the cavitary pressures. Pooled data from six animals with pericardium intact indicate that at RA and RV cavitary pressures of 5, 10, and 15 mm Hg, RV pericardial pressure was 4.3+-0.3, 8.6+-1.0, and 13.3+-1.5 mm Hg, respectively, and RA pericardial pressure was 4.8+-0.3, 9.6+-0.6, and 14.6+-0.6 mm Hg, respectively (mean+-SD). With calculated unstressed dimensions, the cavity dimension data were normalized to strain (in percent). We determined that in the dog, RV strain would increase by 14% and RA by 68% to maintain cavitary pressure at 10 mm Hg on pericardiectomy. To compare these results with clinical data, RV (n=7) and RA (n=6) transmural pressures were measured using balloons in patients (age, 19 to 76 years) undergoing cardiac surgery. RA transmural pressure of six patients was 1.0+-1.5 mm Hg when central venous pressures (CVPs) ranged from 3 to 16 mm Hg. RV transmural pressure equaled 1.2+-1.9, 2.3+-1.9, and 3.4+-2.0 mm Hg when CVP was 5, 10, and 15 mm Hg, respectively.Conclusions Pericardial constraint (as evaluated by the ratio of pericardial to intracavitary pressures when CVP is 10 mm Hg) accounted for 96% of RA cavitary pressure in the dog and 89% in humans and at least 86% of RV cavitary pressure in the dog and 77% in humans.(Circulation. 1994;90:2492-2500.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Certain biphasic waveforms with specific time ratios of positive and negative components require less energy for successful defibrillation of the fibrillating ventricles than monophasic waveforms.However, if more efficient waveforms were also to be associated with more injurious effects on myocardial function, they might not provide a true biological advantage. This study investigates the relation between defibrillation efficacy and potential toxicity of monophasic and asymmetric, single capacitor, biphasic waveforms with equal durations of positive and negative components.Methods and Results The myocardial lactate extraction rate (LER) was used to measure the injurious effects on myocardial oxidative metabolism of two synchronized 35-J shocks in sinus rhythm. LER, mean arterial pressure (MAP) and, in a subset of experiments, cardiac output (CO) and coronary blood flow (CBF) were measured at baseline, 30 seconds, 60 seconds, 90 seconds, 150 seconds, 300 seconds, and 600 seconds after the shocks. In 12 dogs, three different waveforms (M 10: monophasic 10 milliseconds; BI 10: biphasic 10 milliseconds; BI 20: biphasic 20 milliseconds) were tested as series of two consecutive shocks (60 seconds apart) resulting in a total of 36 sets of data. At baseline, LER was 25+-11%. After monophasic shocks, LER decreased significantly more than after biphasic shocks (LER at 150 seconds: M 10: -6+-31% versus BI 10: 21+-15% versus BI 20: 21+-16%; M 10 versus BI 10 and M 10 versus BI 20, P<.05) and showed also a slower recovery (LER at 300 seconds: M 10: 1+-24% versus BI 10: 20+-11% versus BI 20: 20+-15%; M 10 versus BI 10 and M 10 versus BI 20, P<.05). The maximal decrease in LER was 41+-27% for M 10 compared with 18+-15% for BI 10 and 15+-11% for BI 20 (both, M 10 versus BI 10 and M 10 versus BI 20, P<.05). There was a similar decrease in CO and MAP, with the lowest MAP after monophasic shocks. The maximal decrease in MAP was significantly greater after M 10 compared with BI 20 (-29+-15 mm Hg versus -13+-11 mm Hg, P<.05). The defibrillation threshold was 18.6+-8 J for M 10 compared with 11.5+-4.0 J for BI 10 (P<.05) and 15.0+-6.1 J for BI 20, respectively (P=NS).Conclusions Our results suggest that these specific biphasic waveforms are associated with less injurious effects on myocardial oxidative metabolism and hemodynamic performance.Given their higher defibrillation efficacy as well, biphasic waveforms may provide important long-term benefits in patients receiving frequent shocks from implantable cardioverter-defibrillators. (Circulation. 1994;90:2501-2509.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Endothelin (ET) is a potent vasoconstrictor, and its concentration is increased in patients with heart failure.The purpose of this study was to investigate the role of endothelin in heart failure by use of a rat model.15 mm Hg were considered to have chronic heart failure (CHF), while the others were considered to have uncomplicated myocardial infarction (MI). There were increased ET-1 concentrations in CHF rats at weeks 1 to 16 (Sham, 20+-0.5 pg/mL, n=45; CHF, 31+-2 pg/mL, n=50; P<.001) and transient increases in ET-3 concentrations at week 1 in both the MI and CHF groups. There were no significant increases in big ET-1 concentrations, suggesting an increased conversion of ET-1 from big ET-1 in the CHF group. At weeks 2 through 8, oral administration of the mixed (ETAand ETB) endothelin receptor antagonist bosentan significantly decreased mean arterial pressure in conscious CHF rats, an effect that increased over time. Furthermore, bosentan had an additive effect to the angiotensin-converting enzyme inhibitor cilazapril.Conclusions Endothelin plays a role in the maintenance of blood pressure in CHF rats, as evidenced by the significant reduction in mean arterial pressure after oral administration of bosentan.Therefore, endothelin antagonists may be useful therapeutic agents in the treatment of CHF. (Circulation. 1994;90:2510-2518.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Because of the marked difference in the incidence and severity of cardiovascular diseases between men and premenopausal women, several groups have studied the effect of sex steroids, particularly estrogen, on vascular endothelial prostacyclin (PGI2) release.No previous studies have addressed the effect of estrogen on endocardial endothelial cells (EECs), which are involved in the modulation of the myocardium and potentially in downstream pulmonary and systemic vascular tone. Furthermore, all previous studies of estrogen effects on cultured endothelial cell function have used cells grown under standard static cell culture conditions, thereby ignoring the contribution of flow, the ubiquitous environmental endothelial stimulus.Methods and Results The effect of 17 beta -estradiol pretreatment (100 ng/mL, 72 hours) on cultured sheep EEC PGI2release in response to multiple physiologically relevant stimuli was studied. EECs were grown in six-well plates (static conditions) or on microcarrier beads and perfused at a constant flow with normoxic (Po2=150 mm Hg, Pco2=35 mm Hg) or hypoxic (Po2=35 mm Hg, Pco2=35 mm Hg) Krebs solution. The stable metabolite of PGI2, 6-keto-PGF1alpha, was determined in samples from both static and perfusion experiments by direct radioimmunoassay. 17 beta -Estradiol pretreatment did not alter basal or stimulated (arachidonic acid, 1 micromole/L, 10 micromole/L; A23187, 10 micromole/L; and bradykinin, 1 micromole/L) PGI2release in static conditions. Untreated and acutely treated (100 ng/mL added to perfusate) EECs responded to flow with a time-dependent increase in PGI2release that plateaued between 60 and 100 minutes. In contrast, 17 beta -estradiol-pretreated, perfused EECs did not increase PGI2release over time. During perfusion, acute hypoxia increased PGI2release: 140+-65 (normoxia) to 296+-113 pg (hypoxia) 6-keto-PGF1alpha/mg per minute. 17 beta -Estradiol inhibited hypoxia-induced PGI2release: 296+-113 pg (untreated EECs, hypoxia) versus 159+-60 pg (17 beta -estradiol pretreated, hypoxia) 6-keto-PGF1alpha/mg per minute.Conclusions This study demonstrates for the first time an inhibitory effect of 17 beta -estradiol on flow- and acute hypoxia-induced increase in PGI2release from perfused EECs in the absence of any effect on pharmacologically stimulated PGI2release from static cultures. These effects of 17 beta -estradiol may explain in part the well-recognized gender and estrogen effects in cardiovascular diseases and highlight the importance of flow in studies of endothelial cell function. (Circulation. 1994;90:2519-2524.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background The USCI PDA Umbrella is a device to close patent ductus arteriosus (PDA) by a transcatheter technique.Human clinical trials have shown excellent efficacy in reducing or eliminating the PDA shunt, but concerns remain about the risk of infection with this device. The purpose of this study was to evaluate the risk of infection using an animal model.Methods and Results Susceptibility to developing endocarditis was tested by injecting a single intravenous dose of group L streptococcus.Ten piglets with a closed ductus served as controls. Two of these developed valvular vegetations. PDA was produced in 19 animals by balloon dilation of the ductus. Seven of 7 animals with PDA at the time of bacterial injection developed endarteritis of the ductus and valvular vegetations. A PDA Umbrella was placed in the remaining 12 animals, and bacteria were injected 2 weeks after device implantation. Infection was evident in the PDA Umbrella only in the single animal in which the Umbrella had embolized and been left in the left pulmonary artery. Three of the remaining 11 piglets had a significant residual leak, and all developed infection in the ductus and an additional valve. Similar to the control group, none of the animals with complete (n=8) or nearly complete (n=2) closure of the ductus by the PDA Umbrella had infection in or around the ductus, and only 1 had a valvular vegetation.Conclusions In this animal model, presence of a significant PDA shunt (with or without a PDA Umbrella present) results in significantly increased susceptibility to endarteritis and endocarditis.The PDA Umbrella device does not appear to be susceptible to direct infection as early as 2 weeks after implantation if it is properly located in the ductus arteriosus. Animals with no shunt or a trivial shunt are no more susceptible to developing endocarditis 2 weeks after PDA Umbrella implantation than are controls. (Circulation. 1994; 90:2525-2528.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Congestive heart failure is a common, highly lethal cardiovascular disorder claiming over 200 000 lives a year in the United States alone. Some 50% of the deaths in heart failure patients are sudden, and most of these are probably the result of ventricular tachyarrhythmias. Methods designed to identify patients at risk have been remarkably unrewarding, as have attempts to intervene and prevent sudden death in these patients. The failure to impact favorably on the incidence of sudden death in heart failure patients stems largely from a lack of understanding of the underlying mechanisms of arrhythmogenesis. This article explores the role of abnormalities of ventricular repolarization in heart failure patients. We will examine evidence for the hypothesis that alteration of repolarizing K (+) channel expression in failing myocardium predisposes to abnormalities in repolarization that are arrhythmogenic. The possible utility of novel electrophysiological and ECG measures of altered ventricular repolarization will be explored. Understanding the mechanism of sudden death in heart failure may lead to effective therapy and more accurate identification of patients at greatest risk. (Circulation. 1994;90:2534-2539.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID