冠状动脉支架植入术后高凝状态的研究进展

支架内血栓形成是冠状动脉支架植入术后的重要并发症之一,尽管发生率较低,但严重者可危及生命。冠心病支架植入术后高凝状态源自患者的自身因素及支架植入所导致的一系列病理生理反应,包括斑块破裂、血管内皮损伤、组织因子大量表达、微粒生成增多等,进一步可激活血细胞和凝血系统,重者可导致局部血栓形成。及时检测及防治支架术后的高凝状态对降低支架内血栓的发生率有积极作用。本文主要对冠状动脉支架植入术后高凝状态的研究进展进行了综述。     

Stent implantation alters coronary artery hemodynamics and wall shear stress during maximal vasodilation.

Coronary stents improve resting blood flow and flow reserve in the presence of stenoses, but the impact of these devices on fluid dynamics during profound vasodilation is largely unknown. We tested the hypothesis that stent implantation affects adenosine-induced alterations in coronary hemodynamics and wall shear stress in anesthetized dogs (n = 6) instrumented for measurement of left anterior descending coronary artery (LAD) blood flow, velocity, diameter, and radius of curvature. Indexes of fluid dynamics and shear stress were determined before and after placement of a slotted-tube stent in the absence and presence of an adenosine infusion (1.0 mg/min). Adenosine increased blood flow, Reynolds (Re) and Dean numbers (De), and regional and oscillatory shear stress concomitant with reductions in LAD vascular resistance and segmental compliance before stent implantation. Increases in LAD blood flow, Re, De, and indexes of shear stress were observed after stent deployment (P < 0.05). Stent implantation reduced LAD segmental compliance to zero and potentiated increases in segmental and coronary vascular resistance during adenosine. Adenosine-induced increases in coronary blood flow and reserve, Re, De, and regional and oscillatory shear stress were attenuated after the stent was implanted. The results indicate that stent implantation blunts alterations in fluid dynamics during coronary vasodilation in vivo.     

康复运动对冠脉支架植入术后患者相关因素的影响

目的：研究心脏康复运动对冠脉支架植入术后患者血脂、血糖、体重指数及生活质量的影响。方法：对实施冠脉支架植入术的 146例患者进行比较分析，根据随机原则分为试验组76 例及对照组70 例。对照组患者给予常规的健康教育及冠心病二级预防指 导，给予定期随访。试验组患者在此基础上给予规律的康复运动指导。经过6 个月随访，比较两组患者血脂、HbA1C、体重指数及 生活质量情况。结果：试验组患者通过为期6 个月的规律的心脏康复运动指导，其血脂、HbA1C等冠心病危险因素控制情况优于 对照组，差异有统计学意义(P<0.05)。同时，6个月后，试验组康复运动六月后sF 量表各项评分与对照组同期比较，差异均有统计 学意义(P<0.05)。结论：规范的心脏康复运动指导能够有效改善冠脉支架植入术后患者血脂、血糖情况，提高患者生活质量。     

Alterations in regional vascular geometry produced by theoretical stent implantation influence distributions of wall shear stress: analysis of a curved coronary artery using 3D computational fluid dynamics modeling

Background  

The success of stent implantation in the restoration of blood flow through areas of vascular narrowing is limited by restenosis. Several recent studies have suggested that the local geometric environment created by a deployed stent may influence regional blood flow characteristics and alter distributions of wall shear stress (WSS) after implantation, thereby rendering specific areas of the vessel wall more susceptible to neointimal hyperplasia and restenosis. Stents are most frequently implanted in curved vessels such as the coronary arteries, but most computational studies examining blood flow patterns through stented vessels conducted to date use linear, cylindrical geometric models. It appears highly probable that restenosis occurring after stent implantation in curved arteries also occurs as a consequence of changes in fluid dynamics that are established immediately after stent implantation.     

Impact of Coronary Artery Curvature on the Longitudinal Stent Foreshortening: Real-World Observations

Longitudinal stent foreshortening is a known phenomenon, however, the impact of coronary artery curvature on longitudinal stent foreshortening remains unclear. The aim of this study is to determine the impact of coronary artery curvature on the longitudinal stent foreshortening in the real-world scenarios. A total of 86 consecutive patients underwent coronary stent implantation were included in the present study. The degree of coronary artery curvature was defined as the length of the coronary artery curvature divided by the straight length. Longitudinal stent foreshortening was defined as the stent length after implantation divided by the stent length before implantation. The mean longitudinal foreshortening rate of coronary stents was about 94% in curved coronary arteries. Longitudinal stent foreshortening rate was positively correlated with the degree of coronary artery curvature (r = –0.86, P < 0.01). Coronary artery curvature is associated with significant longitudinal foreshortening of coronary stents, thus longitudinal foreshortening should be considered on deciding the stent length in curved coronary artery and a longer stent is usually needed in curved coronary artery.     

Immediate and long-term outcomes of coronary stenting in relation to stent implantation pressure in patients with coronary heart disease

The paper evaluates the pressure impact of implantation of intracoronary stents of different designs on the immediate and long-term outcomes of stenting. A retrospective study included 192 patients. Matrix and wire stents were implanted in 97 (50.5%) and 95 (49.5%) patients, respectively. In one part of the patients, the coronary stent was implanted under nominal pressure, in the other, the stent after implantation was extended with a balloon by using high pressure. Good immediate angiographic and clinical results were obtained in all 192 patients. Thirty three (17.2%) patients were found to have coronary spasm at the site of a stent. There was no significant difference in the development of coronary spasm, which was associated with the type of an implanted (matrix or wire) stent and with the pattern of its implantation (under high or nominal pressure). Dissection along the stent edges developed in 17 of the 192 patients, which amounted to 8.8%. It significantly more frequently developed in patients from Subgroup IA than in those from Subgroup IB. There was no significant difference in the development of restenosis in patients after implantation of matrix or wire stents and in the relation to the stent implantation pressure.     

Circumferential vascular deformation after stent implantation alters wall shear stress evaluated with time-dependent 3D computational fluid dynamics models.

The success of vascular stents in the restoration of blood flow is limited by restenosis. Recent data generated from computational fluid dynamics (CFD) models suggest that stent geometry may cause local alterations in wall shear stress (WSS) that have been associated with neointimal hyperplasia and subsequent restenosis. However, previous CFD studies have ignored histological evidence of vascular straightening between circumferential stent struts. We tested the hypothesis that consideration of stent-induced vascular deformation may more accurately predict alterations in indexes of WSS that may subsequently account for histological findings after stenting. We further tested the hypothesis that the severity of these alterations in WSS varies with the degree of vascular deformation after implantation. Steady-state and time-dependent simulations of three-dimensional CFD arteries based on canine coronary artery measurements of diameter and blood flow were conducted, and WSS and WSS gradients were calculated. Circumferential straightening introduced areas of high WSS between stent struts that were absent in stented vessels of circular cross section. The area of vessel exposed to low WSS was dependent on the degree of circumferential vascular deformation and axial location within the stent. Stents with four vs. eight struts increased the intrastrut area of low WSS in vessels, regardless of cross-sectional geometry. Elevated WSS gradients were also observed between struts in vessels with polygonal cross sections. The results obtained using three-dimensional CFD models suggest that changes in vascular geometry after stent implantation are important determinants of WSS distributions that may be associated with subsequent neointimal hyperplasia.     

血清白细胞介素-18、氧化低密度脂蛋白与急性心肌梗死患者急诊PCI术后支架内再狭窄的关系

目的:探讨血清白细胞介素-18(IL-18)、氧化低密度脂蛋白(ox-LDL)与急诊经皮冠状动脉介入治疗(PCI)术后支架内再狭窄的关系。方法:75例急性心梗急诊介入术后8～12个月内接受冠状动脉造影复查,其中9例有再狭窄作为再狭窄组,66例无再狭窄作为对照组。2组术后均接受阿司匹林、氯吡格雷、他汀类等药物治疗。取2组患者PCI术前、术后冠状动脉造影复查时血清标本,采用酶联免疫吸附法(EL ISA)检测血清IL-18、ox-LDL水平。结果:①再狭窄组PCI术后IL-18、ox-LDL水平较术前均明显升高[(2.37±0.22):(0.85±0.19)mg/L、(6.99±0.98):(2.38±1.06)mg/L],均P<0.01;对照组PCI后IL-18、ox-LDL水平较术前明显下降[(0.48±0.11):(1.23±0.09)mg/L、(1.39±0.54):(4.45±0.87)mg/L],P<0.05。②再狭窄组和对照组PCI术前IL-18、ox-LDL水平差异无统计学意义,再狭窄组PCI术后IL-18、ox-LDL水平显著高于对照组(均P<0.01)。④再狭窄组和对照组术前、术后IL-18和o...     

小型猪冠脉支架模型中即刻OCT检查评价支架贴壁不良的安全性和有效性

目的评价中华小型猪冠状动脉支架植入术后即刻行光学相干断层成像扫描（OCT）的安全性和有效性。方法健康中华小型猪22只,经股动脉途径行右冠状动脉西罗莫司药物洗脱支架植入术,术后即刻行OCT检查评价支架贴壁不良情况,同时记录OCT检查时间和相关并发症。结果 OCT共检查25段支架,失败3例（1例指引导丝断裂于支架内,2例发生冠脉痉挛导致阻断球囊送入困难未能成像）,OCT检查并发症包括一过性ST段抬高（5例）和室颤（3例）,死亡1例,平均手术时间49.7±12.9 min,其中OCT检查耗时17.9±4.9 min,OCT共检测522 mm支架,定量测量4514个支架丝,其中66个存在贴壁不良,即刻支架贴壁不良率1.46%。结论利用冠脉内OCT技术可以有效评价支架术后即刻贴壁不良情况,安全性良好。     

Long-term clinical outcome after stent implantation in coronary arteries

The long-term clinical outcome after planned and unplanned stent implantation was assessed in a single-center, observational study in 178 patients who underwent coronary stent implantation between November 1986 and July 1994. Main outcome measures were survival and event-free survival at 5 years (Kaplan-Meier method). Independent predictors for event-free survival were determined by using multivariate logistic regression analysis. Patients underwent planned (group 1, n 3 101) or unplanned (group 2, n 3 77) stent implantation. During the in-hospital period, there were no deaths. The incidence of Q-wave and non-Q-wave acute myocardial infarction (AMI), coronary artery bypass graft (CABG) and repeat percutaneous transluminal coronary angioplasty (PTCA) was 5.0%, 2.0% and 4.0%, respectively, in group 1, versus 32.5%, 23.4% and 10.4%, respectively, in group 2. During the follow-up period (median 4.0 years, range 0.29-9.8 years), the incidence of death, AMI, and repeat revascularization (CABG and PTCA) was 5.9%, 8.9% and 40.6%, respectively, in group 1, versus 1.3%, 5.2% and 36.4%, respectively, in group 2. Survival and event-free survival at 5 years was 73 (7%) and 47 (7%), respectively, for patients who underwent planned stent implantation. It was 98 (0.1%) and 34 (6%), respectively, for patients who underwent unplanned stent implantation. At the end of follow-up, 31.9% of patients had angina pectoris class III or IV (Canadian Cardiovascular Society). The long-term clinical outcome after both planned and unplanned stent implantation was characterized by a high incidence of repeat revascularization. It is conceivable that changes in stent design and implantation techniques, in addition to novel therapeutic approaches addressing neointima formation and progression of atherosclerosis, may improve the long-term clinical outcome.     

Local hemodynamic analysis after coronary stent implantation based on Euler-Lagrange method

Coronary stents are deployed to treat the coronary artery disease (CAD) by reopening stenotic regions in arteries to restore blood flow, but the risk of the in-stent restenosis (ISR) is high after stent implantation. One of the reasons is that stent implantation induces changes in local hemodynamic environment, so it is of vital importance to study the blood flow in stented arteries. Based on regarding the red blood cell (RBC) as a rigid solid particle and regarding the blood (including RBCs and plasma) as particle suspensions, a non-Newtonian particle suspensions model is proposed to simulate the realistic blood flow in this work. It considers the blood’s flow pattern and non-Newtonian characteristic, the blood cell-cell interactions, and the additional effects owing to the bi-concave shape and rotation of the RBC. Then, it is compared with other four common hemodynamic models (Newtonian single-phase flow model, Newtonian Eulerian two-phase flow model, non-Newtonian single-phase flow model, non-Newtonian Eulerian two-phase flow model), and the comparison results indicate that the models with the non-Newtonian characteristic are more suitable to describe the realistic blood flow. Afterwards, based on the non-Newtonian particle suspensions model, the local hemodynamic environment in stented arteries is investigated. The result shows that the stent strut protrusion into the flow stream would be likely to produce the flow stagnation zone. And the stent implantation can make the pressure gradient distribution uneven. Besides, the wall shear stress (WSS) of the region adjacent to every stent strut is lower than 0.5 Pa, and along the flow direction, the low-WSS zone near the strut behind is larger than that near the front strut. What’s more, in the regions near the struts in the proximal of the stent, the RBC particle stagnation zone is easy to be formed, and the erosion and deposition of RBCs are prone to occur. These hemodynamic analyses illustrate that the risk of ISR is high in the regions adjacent to the struts in the proximal and the distal ends of the stent when compared with struts in other positions of the stent. So the research can provide a suggestion on the stent design, which indicates that the strut structure in these positions of a stent should be optimized further.

     

No influence of hemochromatosis-related gene mutations on restenosis rate in a retrospective study of 137 patients after coronary stent implantation

BACKGROUND: Recent publications have shown an increased risk of coronary artery disease and myocardial infarction in patients with alteration of the hemochromatosis-related gene (HFE gene). The HFE gene mutation is associated with elevated iron uptake and serum iron overloading. Iron plays an important role in promoting the oxidation of LDL cholesterol. The iron deposition in the endothelium and in the media is closely associated with the progression of atherosclerosis. However, it is unclear whether the mutation of the HFE gene also influences the rate of restenosis after coronary stent implantation. METHODS: In a retrospective analysis, 137 patients (pts.) who underwent elective coronary stent implantation were angiographically reevaluated after six months. All patients were part of the OPTICUS-study population which investigated optimized stent implantation guided by intravascular ultrasound. Computerized quantitative analysis was performed in all procedures in a double-blinded fashion. At six-month follow-up, DNA fragments containing the substitution of tyrosine for cytosine at codon 282 were amplified by PCR. The results were analyzed by polyacrylamide gel electrophoresis. Statistical analysis was performed by multivariate linear regression. RESULTS: According to the HFE gene polymorphism we formed two subgroups: 129 pts. (94%) did not show changes in HFE gene (NH), 8 pts. (6%) were heterozygous for HFE Cys282Tyr (H). The groups did not differ in age, gender, extent of coronary artery disease, initial degree and length of stenosis and all patients underwent re-angiography. At six-month follow-up the average luminal narrowing in the stented vessel was 36.2 +/- 20.3% in the NH group compared with 27.8 +/- 20.0% in the H group which was statistically not significant (n. s.). The minimal luminal diameter was 1.9 +/- 0.71 mm in the NH group and 2.2 +/- 0.66 mm in the H group respectively (n. s.). 33 pts (26%) in the NH group versus 2 pts (25%) in the H group had >/= 50% diameter narrowing at follow-up (n. s.). The odds ratio of stent restenosis in H patients was 0.932. CONCLUSIONS: The authors did not find any association between restenosis rate and HFE gene alteration and therefore, we conclude that the polymorphism of the HFE gene is not a risk factor for restenosis after coronary stent implantation.     

Tissue factor, tissue factor pathway inhibitor and cytoadhesive molecules in patients with an acute coronary syndrome

The tissue factor plays a crucial role in initiating blood coagulation after plaque rupture in patients with acute coronary syndrome. It is abundant in atherosclerotic plaques. Moreover, P-selectin, some cytokines, endotoxin and immune complexes can stimulate monocytes and induce the tissue factor expression on their surface. The aim of the study was to compare plasma levels of the tissue factor, tissue factor pathway inhibitor, P-selectin, E-selectin and ICAM-1 in patients with acute myocardial infarction, unstable angina pectoris, stable coronary artery disease and normal control subjects. In addition, plasma levels of the tissue factor, tissue factor pathway inhibitor, P-selectin, E-selectin and ICAM-1 were measured in the blood withdrawn from the coronary sinus in a subgroup of patients with unstable angina pectoris and stable coronary artery disease in which the difference between concentrations in the coronary sinus and systemic blood was calculated. A significant increase in tissue factor pathway inhibitor plasma levels was detected in patients with acute myocardial infarction (373.3+/-135.1 ng/ml, p<0.01) and unstable angina pectoris (119.6+/-86.9 ng/ml, p<0.05) in contrast to the patients with stable coronary artery disease (46.3+/-37.5 ng/ml) and normal subjects (45.1+/-14.3 ng/ml). The plasma levels of tissue factor pathway inhibitor were significantly increased both in the coronary sinus and systemic blood in the patients with unstable angina pectoris. There was only a non-significant trend to higher plasma levels of the tissue factor in patients with acute myocardial infarction and unstable angina pectoris as compared to the patients with stable coronary artery disease and normal subjects, the values being 129.1+/-30.2 pg/ml, 130.5+/-57.8 pg/ml, 120.2+/-45.1 pg/ml and 124.9+/-31.8 pg/ml, respectively. Plasma levels of soluble P-selectin was only slightly, but non-significantly higher in patients with unstable angina pectoris and stable coronary artery disease (184.2+/-85.4 ng/ml and 201.6+/-67.9 ng/ml, respectively) than in patients with the acute myocardial infarction (157.4+/-88.4 ng/ml) or normal subjects (151.4+/-47.1 ng/ml). The difference in plasma levels of soluble ICAM-1 between the blood withdrawn from the coronary sinus and systemic circulation correlated significantly with the corresponding difference in plasma levels of soluble P-selectin and E-selectin. In conclusion, the tissue factor and the tissue factor pathway inhibitor play a crucial role in the initiation of arterial thrombosis. The tissue factor pathway inhibitor levels are increased both in the systemic blood and in the coronary sinus of patients with the acute coronary syndrome.     

Initial and long-term results with the CrossFlex stent--data from a national registry

The Cordis CrossFlex trade mark stent is a balloon expandable helical coil made of stainless steel. OBJECTIVE: To assess the short- and long-term safety and efficacy of this stent by conducting a multi-center national registry. METHODS: One hundred and sixteen stents were implanted in 109 patients (mean age 59 3 10 years, 95 males). The lesions were classified as type B2 or C in 56 patients (51%). Successful deployment was achieved in 103 patients (94.5%). Failure was due to damage to the stent (two patients) or inability to reach the lesion (four patients). High-pressure deployment (>14 atm) was used in 68% of cases. RESULTS: Edge dissections occurred in nine patients after high-pressure deployment and necessitated implantation of a second stent. One patient with a large acute myocardial infarction died during hospitalization. Side branch occlusion occurred in five patients (4.6%). Subacute thrombosis occurred in two patients (1.8%) during the first four weeks. During a six-month follow-up period, 18 patients (16.5%) were rehospitalized with recurrent angina. Fifteen patients had coronary angiography and 13 (12.1%) needed additional target lesion revascularization (TLR). Twelve patients required a second PTCA for in-stent restenosis, and one needed a coronary artery bypass graft operation. CONCLUSIONS: The CrossFlex coronary stent can successfully be used in complex coronary lesions, with few short-term complications and a low TLR rate. Operators should be aware of the possibility of edge dissection during high-pressure implantation.     

Release of TNF-alpha during stent implantation into saphenous vein aortocoronary bypass grafts and its relation to plaque extrusion and restenosis

The reduction in plaque volume during stent implantation is associated with the release of particulate debris and plaque-derived soluble substances. We studied the potential release of the proinflammatory cytokine TNF-alpha into the coronary circulation and whether such release is related to the reduction in plaque volume and, possibly, a predictor for restenosis. In 18 male patients (n = 24 stents) with severe stenosis in a saphenous vein aortocoronary bypass graft (SVG), we used a distal balloon occlusion-aspiration device during stent implantation. The aspirate TNF-alpha levels were determined before and after stent implantation and related to the angiographic and intravascular ultrasound-assessed severity of stenosis and restenosis. We found that TNF-alpha is, indeed, released into the aspirate of stented SVG (9 +/- 1 and 28 +/- 3 pg/ml before and after stent implantation, respectively, P < 0.0001) and that such release is related to the reduction in plaque volume (r = 0.88, P < 0.0001) and associated with restenosis after 5 mo (r = 0.71, P = 0.001). The periprocedural release of plaque-derived TNF-alpha possibly represents the amount and activity of the atherosclerotic process and might be a predictor for restenosis.     

Expression of adrenomedullin in human epicardial adipose tissue: role of coronary status

Epicardial white adipose tissue (eWAT) is in close contact with coronary vessels and therefore could alter coronary homeostasis. Adrenomedullin (AM) is a potent vasodilatator and antioxidative peptide which has been shown to play a cytoprotective role in experimental models of acute myocardial infarction. We studied, using immunohistochemistry and qRT-PCR, the expression of AM and its receptors calcitonin receptor-like receptor (CRLR), and receptor activity-modifying protein (RAMP)2 and -3 in paired biopsies of subcutaneous WAT (sWAT) and eWAT obtained from patients with coronary artery disease (CAD) or without CAD (NCAD). In eWAT obtained from NCAD or CAD patients, immunoreactivity for AM, CRLR, and RAMP2 and -3 was detected in blood vessel walls and isolated stromal cells close to adipocytes. Some of the AM positive stromal cells colocalized CD68 immunoreactivity. eWAT from CAD patients showed increased AM immunoreactivity and AM gene expression. CRLR mRNA levels were comparable in sWAT of both groups and decreased by 40-50% in eWAT, irrespectively of the coronary status. RAMP2 mRNA concentrations did not change while RAMP3 mRNA levels increased in sWAT from CAD patients. There was a positive linear relationship between eWAT 11beta-hydroxysteroid dehydrogenase type 1 mRNA (11beta-HSD-1, the enzyme that converts inactive to active glucocorticoids) and AM mRNA. In conclusion, we demonstrate that AM and its receptors are expressed in eWAT. Our data suggest that eWAT AM, which could originate from macrophages, is related to 11beta-HSD-1 expression. AM synthesis, which is increased in eWAT during chronic CAD in humans, can play a cardioprotective role.     

Adrenomedullin 2 (AM2)/intermedin is a more potent activator of hypothalamic oxytocin-secreting neurons than AM possibly through an unidentified receptor in rats

Central administration of either adrenomedullin 2 (AM2) or adrenomedullin (AM) activates hypothalamic oxytocin (OXT)-secreting neurons in rats. We compared AM2 with AM, given intracerebroventricularly (icv), across multiple measures: (1) plasma OXT levels in conscious rats; (2) blood pressure, heart rate and circulating catecholamine levels in urethane-anesthetized rats; and (3) the expression of the c-fos gene in the supraoptic (SON) and the paraventricular nuclei (PVN). We also tested the effects of the AM receptor antagonist, AM(22-52) and calcitonin gene-related peptide (CGRP) antagonist, CGRP(8-37) on these measures. Plasma OXT levels at 10 min after icv injection of AM (1 nmol/rat) were increased (compared with vehicle), but OXT levels after AM2 (1 nmol/rat) were nearly double the levels seen after AM injection. OXT levels remained elevated at 30 min. Pretreatment with AM(22-52) (27 nmol/rat) and CGRP(8-37) (3 nmol/rat), nearly abolished the increase in plasma OXT level after AM injection, but partially blocked OXT level changes due to AM2. Increases in blood pressure, heart rate and circulating catecholamines were all greater in response to central AM2 than to AM at the same dose. In situ hybridization histochemistry showed that both AM2 and AM induced expression of the c-fos gene in the SON and the PVN, but AM(22-52)+CGRP(8-37) could only nearly abolish the effects of centrally administered AM. These results suggest that the more potent central effects of AM2 and only partial blockade by AM/CGRP receptor antagonists may result from its action on an additional, as yet unidentified, specific receptor in the central nervous system.     

The role of lipopolysaccharide in stimulating adrenomedullin production during polymicrobial sepsis

Previous studies have shown that adrenomedullin (AM), a potent vasodilatory peptide, is upregulated during sepsis. However, it remains unknown whether the increased AM observed under such conditions is solely due to the elevated levels of circulating lipopolysaccharide (LPS). To determine this, an Alzet micro-osmotic pump, containing a low dose of Escherichia coli LPS or vehicle (sterile normal saline), was implanted in the peritoneal cavity of the normal male adult rat. At 10 h after the pump implantation, samples of blood and small intestine were harvested for the determination of AM by radioimmunoassay. In additional groups, rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). LPS binding agent polymyxin B was administrated intramuscularly at 1 h prior to as well as 5 h after the onset of sepsis. At 10 h after CLP or sham-operation, blood and intestinal samples were harvested and levels of AM were then determined. Plasma levels of LPS were also measured by Limulus amebocyte lysate assay. The results indicate that administration of a low dose of LPS via the peritoneal cavity in normal animals (which did not significantly alter cardiac output, blood pressure or heart rate) markedly increased plasma and intestinal levels of AM. In addition, plasma and tissue levels of AM increased significantly at 10 h after CLP. Administration of polymyxin B, however, attenuated the increase in AM levels under such conditions. Similarly, the increased plasma levels of LPS was significantly reduced by polymyxin B during sepsis. These results, taken together, suggest that the upregulated AM observed during polymicrobial sepsis is at least in part due to the increase in circulating levels of endotoxin.