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 Experimental evidence suggests that flow-dependent dilatation of conduit arteries is mediated by nitric oxide (NO) and/or prostacyclin. The present study was designed to assess whether NO or prostacyclin also contributes to flow-dependent dilatation of conduit arteries in humans.Methods and Results Radial artery internal diameter (ID) was measured continuously in 16 healthy volunteers (age, 24+-1 years) with a transcutaneous A-mode echo-tracking system coupled to a Doppler device for the measurement of radial blood flow. In 8 subjects, a catheter was inserted into the brachial artery for measurement of arterial pressure and infusion of the NO synthase inhibitor NG-monomethyl-l-arginine (L-NMMA; 8 micromole/min for 7 minutes; infusion rate, 0.8 mL/min). Flow-dependent dilatation was evaluated before and after L-NMMA or aspirin as the response of the radial artery to an acute increase in flow (reactive hyperemia after a 3-minute cuff wrist occlusion). Under control conditions, release of the occlusion induced a marked increase in radial blood flow (from 24+-3 to 73+-11 mL/min; P<.01) followed by a delayed increase in radial diameter (flow-mediated dilatation; from 2.67+-0.10 to 2.77+-0.12 mm; P<.01) without any change in heart rate or arterial pressure. L-NMMA decreased basal forearm blood flow (from 24+-3 to 13+-3 mL/min; P<.05) without affecting basal radial artery diameter, heart rate, or arterial pressure, whereas aspirin (1 g PO) was without any hemodynamic effect. In the presence of L-NMMA, the peak flow response during hyperemia was not affected (76+-12 mL/min), but the duration of the hyperemic response was markedly reduced, and the flow-dependent dilatation of the radial artery was abolished and converted to a vasoconstriction (from 2.62+-0.11 to 2.55+-0.11 mm; P<.01). In contrast, aspirin did not affect the hyperemic response nor the flow-dependent dilatation of the radial artery.Conclusions The present investigation demonstrates that NO, but not prostacyclin, is essential for flow-mediated dilatation of large human arteries. Hence, this response can be used as a test for the l-arginine/NO pathway in clinical studies. (Circulation. 1995;91:1314-1319.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background The purpose of this pilot study was to identify biological risk factors for restenosis after percutaneous transluminal coronary angioplasty (PTCA) to predict the long-term outcome of PTCA before treatment.Methods and Results To investigate whether blood granulocytes and monocytes could determine luminal renarrowing after PTCA, several characteristics of these phagocytes were assessed before angioplasty in 32 patients who underwent PTCA of one coronary artery and who had repeat angiograms at 6-month follow-up. The plasma levels of interleukin (IL)-1 beta, tumor necrosis factor-alpha, IL-6, fibrinogen, C-reactive protein, and lipoprotein(a) before angioplasty were assessed as well. We found that the expression of the membrane antigens CD64, CD66, and CD67 by granulocytes was inversely associated with the luminal renarrowing normalized for vessel size (relative loss) at 6 months after PTCA, while the production of IL-1 beta by stimulated monocytes was positively associated with the relative loss. Next, these univariate predictors were corrected for the established clinical risk factors of dilation of the left anterior descending coronary artery and current smoking, which were statistically significant classic predictors in our patient group. Only the expression of CD67 did not predict late lumen loss independent of these established clinical risk factors. Multiple linear regression analysis showed that luminal renarrowing could be predicted reliably (R2=.65; P<.0001) in this patient group on the basis of the vessel dilated and only two biological risk factors that reflect the activation status of blood phagocytes, ie, the expression of CD66 by granulocytes and the production of IL-1 beta by stimulated monocytes.Conclusions The results of the present study indicate that activated blood granulocytes prevent luminal renarrowing after PTCA, while activated blood monocytes promote late lumen loss. To validate this new finding, further study in an independent patient group is required. (Circulation. 1995;91:1320-1325.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Heart-hand syndromes compose a class of combined congenital cardiac and limb deformities. The prototypical heart-hand disorder is Holt-Oram syndrome, which is characterized by cardiac septation defects and radial ray limb deformity. We have recently mapped the Holt-Oram syndrome gene defect to the long arm of human chromosome 12 in two families. The role of this disease locus in the pathogenesis of related conditions such as heart-hand syndrome type III (cardiac conduction disease accompanied by skeletal malformations) or familial atrial septal defects is unknown.Methods and Results Clinical evaluations and genetic linkage analyses were performed in five additional kindreds with Holt-Oram syndrome and also in one kindred with heart-hand syndrome type III and one kindred with familial atrial septal defect and conduction disease. Holt-Oram syndrome in all five kindreds mapped to chromosome 12q2. These studies and previous data provide odds of greater than 1025:1 that the Holt-Oram syndrome disease gene is at chromosome 12q2. In contrast, neither the phenotypically similar disorder heart-hand syndrome type III nor the locus responsible for a familial atrial septal defect with atrioventricular block maps to chromosome 12q2.Conclusions We demonstrate that heart-hand syndromes are genetically heterogeneous. Conditions that clinically appear to be partial phenocopies of Holt-Oram syndrome arise from distinct disease genes. (Circulation. 1995;91:1326-1329.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background The extent and mechanism of the antithrombotic properties of fibrin-selective and non-fibrin-selective thrombolytic agents have not yet been established.Methods and Results The antithrombotic, thrombolytic, fibrinogenolytic, and pharmacokinetic properties of the following substances were determined in hamsters in the absence of conjunctive anticoagulant or antiplatelet therapy: recombinant tissue-type plasminogen activator (rTPA), recombinant single-chain urokinase-type plasminogen activator (rscu-PA), two-chain urokinase-type plasminogen activator (UK), with a rTPA deletion mutant lacking amino acids 6 to 173 and a mutation N184E (K2Pt), a rTPA/rscu-PA chimeric plasminogen activator consisting of amino acids 1 to 3 and 87 to 274 of rTPA and amino acids 138 to 411 of rscu-PA (K1K2Pu), streptokinase (SK), and recombinant staphylokinase (STAR). The antithrombotic effect, defined as the intravenous dose required to reduce mural thrombus formation to 50% in a platelet-mediated femoral vein thrombosis model in the hamster, was 6+-1, 5+-2, 1+-0.05, 2.5+-0.2, 0.02+-0.002, 1+-0.09, and 2+-0.3 mg/kg (mean+-SEM), respectively. The amounts, given as intravenous infusion over 60 minutes that induced 50% clot lysis in a hamster pulmonary embolism model, were 0.18+-0.03, 1.1+-0.05, 0.9+-0.13, 0.34+-0.03, 0.04+-0.003, 0.05+-0.005, and 0.04+-0.001 mg/kg, respectively, indicating that for most thrombolytic agents the antithrombotic dose is much higher than their thrombolytic dose. The fibrinogen levels, measured 40 minutes after bolus injection, were reduced to 50% of baseline with 3.1+-0.2, 2.5+-0.3, 1.2+-0.08, 2.0+-0.14, 1.7+-0.65, 0.54+-0.03, and 1.2+-0.11 mg/kg, respectively. Mean residence times following intravenous bolus injection were: 18+-1, 14+-1, 100+-10, 80+-2, 20+-3, and 34+-5 minutes for rTPA, rscu-PA, K2Pt, K1K2Pu, SK, and STAR, respectively. Regression analysis revealed a significant correlation of the antithrombotic effect with the fibrinogen breakdown (P=.006) but not with the thrombolytic potency or with the mean residence time.Conclusions These observations support the hypothesis that thrombolytic therapy with fibrinogen-sparing agents requires the conjunctive use of anticoagulant and/or antiplatelet agents. (Circulation. 1995;91:1330-1335.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Cocaine consumption has been associated with thrombosis of coronary and peripheral arteries. Since cocaine has been found to induce platelet activation in vitro, we sought to establish whether cocaine induced platelet activation in vivo.Methods and Results Chronically instrumented, conscious dogs were infused with cocaine (1 mg/kg), norepinephrine (0.2 to 0.4 mg/kg), or saline intravenously over 1 minute. Activated canine platelets were identified in whole blood collected from an indwelling aortic catheter by flow cytometric detection of the binding of a monoclonal antibody directed against the activation-dependent antigen P-selectin. Infusion of cocaine resulted in an elevation of mean arterial pressure (91+-3 to 128+-7 mm Hg (P<.001)) and heart rate (87+-9 to 125+-11 beats per minute (P<.01)). A similar change (P=NS) in mean arterial pressure followed norepinephrine infusion (100+-5 to 137+-13 mm Hg (P<.04)), whereas saline infusion had no effect. Cocaine resulted in a substantial but delayed increase in platelet P-selectin expression (14+-7% (P<.08), 31+-12% (P<.04), and 55+-22% (P<.04) at 17, 22, and 27 minutes after drug infusion, respectively). The magnitude of this increase was similar to that found in blood treated ex vivo with the agonists ADP or PAF (23+-7% and 53+-15%, respectively). No significant increase in P-selectin expression was detected in the blood of animals that received norepinephrine or saline. Serum cocaine concentrations were highest immediately after infusion (538+-55 ng/mL at 2 minutes) but declined rapidly (185+-22 and 110+-25 ng/mL at 17 and 32 minutes after infusion); in contrast, the increase in benzoylecgonine concentrations was delayed (from <25 ng/mL in all but one animal (34 ng/mL) at 2 minutes to 46+-4 and 71+-11 ng/mL at 17 and 32 minutes, respectively, after infusion).Conclusions Intravenous cocaine induces activation of individual circulating platelets; this effect is not reproduced by infusion of norepinephrine at doses sufficient to exert similar hemodynamic effects. The delay in detection of activated platelets after treatment with cocaine may result from the adhesion and subsequent detachment of activated platelets; alternatively, cocaine metabolites, rather than the drug itself, may induce platelet activation. (Circulation. 1995;91:1336-1340.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background The frequency of onset of acute myocardial infarction follows a circadian pattern, with a peak incidence between 6:00 am and noon. Circadian variations have been defined for platelet aggregation, plasminogen-activator inhibitor, and a number of hemostatic and physiological factors, all of which might predispose toward clotting in the late morning and thrombolysis in the evening. Thus, the hypothesis for this retrospective analysis was that tissue-type plasminogen activator (TPA) has greater efficacy when administered between noon and midnight, as measured by coronary patency 90 minutes after initiation of treatment.Methods and Results Seven hundred twenty-eight patients were enrolled in either of two studies in which TPA was administered under a uniform protocol for the treatment of acute myocardial infarction. Of these, 692 patients had qualifying arteriograms that allowed standardized assessment by a core angiographic laboratory of the primary end point of 90-minute patency. TPA has a circadian pattern of efficacy, with greater TIMI grade 3 patency when administered between noon and midnight (P<.001). When TPA was given within 2 hours of symptoms (n=127), the total patency was highest and there was a trend (P=.055) toward the greatest magnitude difference occurring between am and pm patency. The onset of myocardial infarction was confirmed to have a marked circadian variation with a peak incidence about 10:00 am. The peak efficacy of TPA was about 8:00 pm, representing a phase difference of about 10 hours after peak infarction incidence.Conclusions There is a circadian variation in the ability of TPA to rapidly open coronary arteries, with highest efficacy between noon and midnight. This complements clinical and in vitro knowledge of increased morning thrombosis and is concordant with knowledge of a fibrinolytic profile that is more favorable for evening lysis. This finding has implications for understanding the circadian pathophysiology of myocardial infarction and for its chronotherapy. (Circulation. 1995;91:1341-1346.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background In survivors of myocardial infarction, restoration of antegrade flow in the infarct artery reduces morbidity and mortality. At present, coronary artery patency must be assessed invasively with contrast angiography. A noninvasive method of evaluating infarct artery patency would be useful in managing survivors of infarction. This study was performed to determine whether magnetic resonance (MR) imaging could reliably assess infarct artery patency in this patient population.Methods and Results Eighteen survivors of myocardial infarction (11 men and 7 women, aged 35 to 74 years) who were consecutively referred for cardiac catheterization underwent contrast coronary angiography and cine MR coronary angiography. Sequential overlapping images of the infarct artery were acquired with cine MR during 15- to 20-second periods of breath-holding. In each study, proximal, middle, and distal segments of infarct arteries were classified as having antegrade, collateral, or no flow. The infarct artery was the left anterior descending in 10 patients, the right anterior descending in 7, and the circumflex in 1. When compared with the results of contrast angiography, MR imaging correctly identified the presence or absence of antegrade flow in the infarct artery of all 18 patients. In addition, cine MR coronary angiography with presaturating pulses correctly established the presence or absence of collateral filling of the distal portion of occluded arteries in 6 of 7 subjects.Conclusions In survivors of myocardial infarction, cine MR coronary angiography can reliably determine the patency and direction of flow in the infarct artery. (Circulation. 1995;91: 1347-1353.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background A real-time in vitro system of human platelet thrombosis under arterylike flowing conditions similar to those produced in vivo by angioplasty would be useful for the evaluation of potential antiarterial thrombotic agents in association with in vivo trials. Aspirin, heparin, and the chimeric monoclonal antibody antigen-binding fragment 7E3 (c7E3 Fab) directed against platelet glycoprotein (GP) IIb-IIIa have been used in attempts to delay or prevent thrombotic reocclusion of coronary arteries after angioplasty. We compared the effects of these agents administered in vivo on GPIb-mediated platelet adhesion to von Willebrand factor (vWF)/collagen type I (as in atherosclerotic subendothelium) and on subsequent GPIIb-IIIa-fibrinogen/vWF-mediated platelet aggregation under flowing conditions analogous to those in constricted coronary arteries.Methods and Results Citrated whole blood containing mepacrine-labeled platelets from patients and healthy donors was perfused for 1 minute at an abnormally elevated shear rate of 1500 seconds sup -1 (arterial wall shear stress of 50 to 60 dynes/cm250% inhibition of platelet aggregation 2 minutes after the infusion of c7E3 Fab in all 3 patients, and inhibition persisted in 2 of the 3 patients at 2 hours and 24 hours after c7E3 Fab.Conclusions In contrast to aspirin or heparin, the in vivo injection of c7E3 Fab considerably reduces platelet aggregate formation mediated by the binding of fibrinogen, vWF, or some other ligand to platelet GPIIb-IIIa under conditions of abnormally increased shear stress analogous to those in narrowed coronary arteries. Platelet adherence to collagen I/vWF is not affected. This study describes an in vitro model of arterial injury (similar to angioplasty) that uses human blood to compare directly, in real time, the precise relative effects of aspirin, heparin, and c7E3 Fab on platelet adhesion and subsequent aggregation. (Circulation. 1995;91:1354-1362.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID