Coronary aspirate TNFα reflects saphenous vein bypass graft restenosis risk in diabetic patients

Background

Patients with diabetes mellitus (DM) have an increased risk for periprocedural complications and adverse cardiac events after percutaneous coronary intervention. We addressed the potential for coronary microvascular obstruction and restenosis in patients with and without DM undergoing stenting for saphenous vein bypass graft (SVG) stenosis under protection with a distal occlusion/aspiration device.

Methods

SVG plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Percent diameter stenosis was determined from quantitative coronary angiography before, immediately after and 6?months after stent implantation. Coronary aspirate was retrieved during stent implantation and divided into particulate debris and plasma. Total calcium, several vasoconstrictors, and tumor necrosis factor (TNF)α in particulate debris and coronary aspirate plasma were determined.

Results

Patients with and without DM had similar plaque volume, but larger necrotic core and greater particulate debris release in patients with than without DM (20.3±2.7 vs. 12.7±2.6% and 143.9±19.3 vs. 75.1±10.4?mg, P<0.05). The TNFα concentration in particulate debris and coronary aspirate plasma was higher in patients with than without DM (15.9±6.6 vs. 5.1±2.4 pmol/mg and 2.2±0.7 vs. 1.1±0.2 pmol/L, P<0.05), whereas total calcium and vasoconstrictors were not different. Patients with DM had a greater percent diameter stenosis 6?months after stent implantation than those without DM (22.17±5.22 vs. 6.34±1.11%, P<0.05). The increase in TNFα immediately after stent implantation correlated with restenosis 6?months later (r=0.69, P<0.05).

Conclusion

In diabetics, particulate debris and coronary aspirate plasma contained more TNFα, which might reflect the activity of the underlying atherosclerotic process.

Trial registration

URL: http://www.clinicaltrials.gov/ct2/results?term=NCT01430884; unique identifier: NCT01430884     

良性中心气道狭窄支气管镜介入治疗术后近远期再狭窄相关因素分析

目的探讨良性中心气道狭窄支气管镜介入治疗术后近远期再狭窄相关因素。方法对2011年2月~2015年2月我院收治的60例良性中心气道狭窄患者经支气管镜下介入治疗,治疗方式包括高频电刀、冷冻、球囊扩张、金属覆膜支架置入等。治疗后对患者的治疗时机、局部感染情况、治疗方法、气道狭窄病因、年龄、性别、基础疾病等情况进行分析,随访观察评估术后疗效、出现再狭窄的时间,探讨近远期再狭窄的危险因素。结果 Cox回归分析表明,患有基础疾病(高血压、糖尿病)、球囊扩张、支架置入、治疗时机不当(溃疡坏死增值阶段)、局部感染是良性气管狭窄支气管镜下腔内介入治疗术后近期再狭窄的相关危险因素,其对再狭窄影响的风险比(OR值)依次为6.715、2.197、5.820、6.914、5.345。支架置入和治疗时机不当(溃疡坏死增值阶段)是良性气管狭窄支气管镜下腔内介入治疗术后远期再狭窄的相关危险因素,其对再狭窄影响的风险比(OR值)分别为6.706,7.154。结论良性中心气道狭窄患者支气管镜下腔内介入治疗术后近期再狭窄的危险因素是基础疾病、球囊扩张、支架置入、局部感染、治疗时机不当,远期再狭窄危险因素是支架置入和治疗时机不当。     

Inhibition of in-stent restenosis by oral copper chelation in porcine coronary arteries

Stress-induced release of IL-1alpha and fibroblast growth factor-1 is dependent on intracellular copper and is a major driver of neointimal hyperplasia. Therefore, we assessed the effect of tetrathiomolybdate (TTM), a clinically proven copper chelator, on in-stent restenosis. Nine pigs were treated with TTM (5 mg/kg po) twice daily for 2 wk before stent implantation and for 4 wk thereafter, and nine pigs served as controls. In-stent restenosis was assessed by quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), and histomorphometry. Serum ceruloplasmin activity was used as a surrogate marker of copper bioavailability. In TTM-treated animals, ceruloplasmin dropped 70 +/- 10% below baseline levels. Baseline characteristics were comparable in TTM-treated and control animals. At 4-wk follow-up, all parameters relevant to in-stent restenosis were significantly reduced in TTM-treated animals: minimal lumen diameter by QCA was 2.03 +/- 0.57 and 1.47 +/- 0.45 mm in TTM-treated and control animals, respectively (P < 0.05), percent stenosis diameter was 39% less in TTM-treated animals (27.1 +/- 16.6% vs. 44.5 +/- 16.1%, P < 0.05), minimal lumen area by IVUS was 60% larger in TTM-treated animals (4.27 +/- 1.56 vs. 2.67 +/- 1.19 mm(2), P < 0.05), and neointimal volume by histomorphometry was 37% less in TTM-treated animals (34.9 +/- 11.5 vs. 55.2 +/- 19.6 mm(3), P < 0.05). We conclude that systemic copper chelation with a clinically approved chelator significantly inhibits in-stent restenosis.     

Coronary stent implantation changes 3-D vessel geometry and 3-D shear stress distribution

Mechanisms of in-stent restenosis are not fully understood. Shear stress is known to play a role in plaque and thrombus formation and is sensitive to changes in regional vessel geometry. Hence, we evaluated the regional changes in 3-D geometry and shear stress induced by stent placement in coronary arteries of pigs.Methods. 3-D reconstruction was performed, applying a combined angiographic and IVUS technique (ANGUS), from seven Wallstents (diameter 3.5 (n=3) and 5mm (n=4)), which were implanted in seven coronary arteries of five pigs. This 3-D geometry was used to calculate locally the curvature, while the shear stress distribution was obtained by computational fluid dynamics. Local changes in shear stress were obtained at the entrance and exit of the stent for baseline (0. 65+/-0.22 ml/s) and hyperemic flow (2.60+/-0.86 ml/s) conditions. Results. After stent implantation, the curvature increased by 121% at the entrance and by 100% at the exit of the stent, resulting in local changes in shear stress. In general, at the entrance of the stent local maxima in shear stress were generated, while at the exit both local maxima and minima in shear stress were observed (p<0.05). Additionally, the shear stress at the entrance and exit of the stent were correlated with the local curvature (r: 0.30-0.84).Conclusion. Stent implantation changes 3-D vessel geometry in such a way that regions with decreased and increased shear stress occur close to the stent edges. These changes might be related to the asymmetric patterns of in-stent restenosis.     

阿托伐他汀对颈动脉狭窄并支架置入术后患者临床预后及炎症因子的影响

目的：研究阿托伐他汀对颈动脉狭窄并支架置入术后患者临床预后及炎症因子的影响。方法：选取2013 年1 月到2014 年1 月我院收治的接受支架置入术的颈动脉狭窄患者90例,按照随机数字表法将患者分为研究组和对照组,每组45 例,对照组给予 常规治疗,研究组在对照组的基础上给予阿托伐他汀治疗,连续治疗1 年,比较两组支架内再狭窄率及不良反应发生率,分析治 疗前和治疗后两组超敏C反应蛋白（hs-CRP）、白细胞介素-6（IL-6）水平。结果：研究组1 年内支架再狭窄率显著低于对照组,两 组比较差异具有统计学意义（P＜0.05）;治疗后两组hs-CRP 和IL-6 水平均显著低于治疗前,且研究组显著低于对照组,比较差异 具有统计学意义（P＜0.05）;两组不良反应比较无统计学意义（P＞0.05）。结论：阿托伐他汀治疗颈动脉狭窄并支架置入术患者,能 显著降低支架内再狭窄率及炎症因子水平。     

Clinical and quantitative angiographic outcomes following elective implantation of the self-expanding Wallstent for longer coronary artery lesions--final results of the Wellstent native study

BACKGROUND: Implantation of short balloon-expandable stents provides superior clinical and angiographic outcome compared with balloon angioplasty in selected patients. The purpose of the Wellstent study was to evaluate the safety and efficacy of the self-expanding Wallstent combined with aspirin and ticlopidine in patients with stable or unstable angina related to a native coronary lesion up to 45 mm in length. METHODS: 105 patients (111 lesions) with stable (57%) or unstable (43%) angina were included in this prospective multicentre evaluation. Angiography before and after Wallstent implantation and at 6-month follow-up was analysed at the core lab using the CAAS 2 system. The primary end-point was incidence of major adverse cardiac events (MACE) at 30 days. Secondary end-points were angiographic outcome at 6 months and MACE at 6 months and 1 year. RESULTS: Acute procedural success (successful stent implantation with residual stenosis <20%) was achieved in 99%. Mean reference diameter was 3.18 +/- 0.66 mm, minimal luminal diameter was 1.00 +/- 0.50 mm pre- and 2.84 +/- 0.47 mm poststent (diameter stenosis 16 +/- 6%). The mean hospital stay was 2.2 days. At 30 days, 95% of patients were free of MACE. At 6 month and 1 year clinical follow-up, 75% and 71% of patients, respectively, remained free of MACE, the majority of which (19 of 30) were re-interventions at re-angiography. In 90% of eligible patients, MLD at follow-up was 1.65 +/- 0.75 mm (late loss 1.20 +/- 0.66 mm, loss index 0.66), diameter stenosis 42 +/- 15%, with a restenosis rate of 32%. Longer stents were associated with greater luminal loss (P = 0.001) and less-favourable clinical outcome. CONCLUSIONS: Wallstent implantation, combined with aspirin and ticlopidine, achieved excellent acute and 30 day clinical results in a heterogenous high-risk patient group. Clinical outcome at 6 months and 1 year remained good, and most adverse events were re-PTCA during follow-up angiography. The loss index of 0.66 and restenosis rate of 32%, related in part to the use of longer stents, emphasizes the continuing need for effective anti-proliferative therapy.     

The role of acute wall recoil and late restenosis: results of the OCBAS trial (Optimal Coronary Balloon Angioplasty with Provisional Stenting versus Primary Stent)

Early deterioration of minimal luminal diameter immediately after PTCA, has been associated with an increase of late restenosis. Lesions with no early loss after PTCA have a low restenosis rate. Coronary stents reduce restenosis in lesions exhibiting early wall recoil. The purpose of the OCBAS study was to compare two strategies during coronary interventions; provision vs. elective stenting. 116 patients with good PTCA results were randomized to stent (n = 57) or to optimal PTCA (n = 59). After randomization in PTCA group, 13.5% of the patients crossed over to stent due to early loss (provisional stenting). Baseline demographic and angiographic characteristics were similar in both groups of patients. At 7.6 months, 96.6% of the entire population had a follow-up angiographic study; 98.2% in the stent and 94.9% in the PTCA group. Immediate and follow-up angiographic data showed that acute gain was significantly higher in the stent than in the PTCA group (1.95 vs. 1.5 mm; P < 0.03). However, late loss was significantly higher in the stent than the PTCA groups (0.63 +/- 0.59 vs. 0.26 +/- 0.44, respectively; P = 0.01). Hence, net gain with both techniques was similar (1.32 +/- 0.3 vs. 1.24 +/- 0.29 mm for the stent and PTCA groups respectively; P = NS). Angiographic restenosis rate at follow-up (19.2% in stent vs. 16.4% in PTCA; P = NS) and TVR (17.5 in stent vs. 13.5% in PTCA; P = NS) were also similar. Furthermore, event-free survival was 80.8% in the stent versus 83.1% in the PTCA group (P = NS). Overall costs (hospital and follow-up) were US$591,740 in the stent versus US$398,480 in the PTCA group (P < 0.02). The strategy of the PTCA with delay angiogram and provisional stent if early loss occurs, had similar restenosis rate and TVR than universal use of bare stents.     

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.     

Release of Intracoronary Microparticles during Stent Implantation into Stable Atherosclerotic Lesions under Protection with an Aspiration Device

Objective

Stent implantation into atherosclerotic coronary vessels impacts on downstream microvascular function and induces the release of particulate debris and soluble substances, which differs qualitatively and quantitatively between native right coronary arteries (RCAs) and saphenous vein grafts on right coronary arteries (SVG-RCAs). We have now quantified the release of microparticles (MPs) during stent implantation into stable atherosclerotic lesions and compared the release between RCAs and SVG-RCAs.

Methods

In symptomatic, male patients with stable angina and a stenosis in their RCA or SVG-RCA, respectively (n = 14/14), plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Coronary aspirate was retrieved during stent implantation with a distal occlusion/aspiration device and divided into particulate debris and plasma. Particulate debris was weighed. Platelet-derived MPs (PMPs) were distinguished by flow cytometry as CD41⁺, endothelium-derived MPs (EMPs) as CD144⁺, CD62E⁺ and CD31⁺/CD41^-, leukocyte-derived MPs as CD45⁺, and erythrocyte-derived MPs as CD235⁺.

Results

In patients with comparable plaque volume and composition in RCAs and SVG-RCAs, intracoronary PMPs and EMPs were increased after stent implantation into their RCAs and SVG-RCAs (CD41⁺: 2729.6±645.6 vs. 4208.7±679.4 and 2355.9±503.9 vs. 3285.8±733.2 nr/µL; CD144⁺: 451.5±87.9 vs. 861.7±147.0 and 444.6±74.8 vs. 726.5±136.4 nr/µL; CD62E⁺: 1404.1±247.7 vs. 1844.3±378.6 and 1084.6±211.0 vs. 1783.8±384.3 nr/µL, P<0.05), but not different between RCAs and SVG-RCAs.

Conclusion

Stenting in stable atherosclerotic lesions is associated with a substantial release not only of PMPs, but also of EMPs in RCAs and SVG-RCAs. Their release does not differ between RCAs and SVG-RCAs.

Trial Registration

ClinicalTrials.gov NCT01430884     

Mechanistic evaluation of long-term in-stent restenosis based on models of tissue damage and growth

Development and application of advanced mechanical models of soft tissues and their growth represent one of the main directions in modern mechanics of solids. Such models are increasingly used to deal with complex biomedical problems. Prediction of in-stent restenosis for patients treated with coronary stents remains a highly challenging task. Using a finite element method, this paper presents a mechanistic approach to evaluate the development of in-stent restenosis in an artery following stent implantation. Hyperelastic models with damage, verified with experimental results, are used to describe the level of tissue damage in arterial layers and plaque caused by such intervention. A tissue-growth model, associated with vessel damage, is adopted to describe the growth behaviour of a media layer after stent implantation. Narrowing of lumen diameter with time is used to quantify the development of in-stent restenosis in the vessel after stenting. It is demonstrated that stent designs and materials strongly affect the stenting-induced damage in the media layer and the subsequent development of in-stent restenosis. The larger the artery expansion achieved during balloon inflation, the higher the damage introduced to the media layer, leading to an increased level of in-stent restenosis. In addition, the development of in-stent restenosis is directly correlated with the artery expansion during the stent deployment. The correlation is further used to predict the effect of a complex clinical procedure, such as stent overlapping, on the level of in-stent restenosis developed after percutaneous coronary intervention.

     

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...     

中性粒细胞／淋巴细胞比值与药物支架内再狭窄关系

目的：探讨经皮冠状动脉支架植入术前中性粒细胞／淋巴细胞比值（Neutrophil-to-LymphocyteRatio,NLR）与患者药物支架（DrugElutingStent,DES）植入后发生支架内再狭窄（In—StentRestenosis,ISR）的关系。方法：回顾性分析2012年01月至2012年10月间有DES植入史并再次入院接受冠脉造影的92例患者（平均年龄65．22±9．73岁）的血液学检查、既往冠脉造影结果及再次冠脉造影结果。根据DES植入前的NLR的四分位点将所有入选患者分为3组：最低三分位组（n=31,0．91-1．83）,中间三分位（n=30,1．87—2．63）,最高三分位（n=31,2．66—4．67）,比较3组间ISR发生率有无差异。结果：再狭窄发生在最低NLR三分位的有3例（9．68％）,发生在中间NLR三分位组的有2例（6．67％）,而有4例（12．90％）发生在NLR最高三分位组（P=0．714）,3组之间的差异无统计学意义。结论：因稳定或不稳定型心绞痛而植入药物支架的患者,其术前NLR同支架术后ISR的发生无明显相关性。NLR不能作为DES植入后发生再狭窄的预测指标。     

Clinical and angiographic results with the NIR stent: First International NIR Endovascular Stent Study (FINESS-II)

BACKGROUND: Although safety and efficacy of the NIR trade mark stent have been reported, the long-term angiographic and clinical outcomes have yet to be investigated. The FINESS-II study (First International NIR Endovascular Stent Study) was designed to assess the procedural safety of single 9 and 16 mm NIR stent implantation, the six-month restenosis rate and finally the six- and 12-month clinical outcome of patients treated with this novel coronary stent. METHODS: Patients with angina and a single de novo lesion in a native coronary artery of >3 and <5 mm diameter were included in this multicentre, prospective, observational trial. Clinical follow-up was obtained at one, six and 12 months. Angiography was performed before and after the stent implantation and at six months. The primary endpoint included major adverse cardiac events (death, myocardial infarction and target lesion revascularization) within 30 days after the procedure. Major bleeding complications and subacute stent thrombosis within the first 30 days were also reported as specific endpoints. Secondary endpoints were major cardiac-event-free survival at six- and 12-month follow-up and angiographic restenosis at six months. RESULTS: A total of 156 patients (81% male, mean age 60 +/- 10 years), with stable (54%), unstable (40%) angina pectoris or silent ischemia (6%) were enrolled. The target vessel diameter was 2.94 +/- 0.54 mm. The minimal lumen diameter pre, post and at follow-up was 1.04 +/- 0.32 mm, 2.64 +/- 0.42 mm and 1.88 +/- 0.63 mm, respectively. Restenosis rate according to the >50% diameter stenosis criterion at six month follow-up was 19% (26/136). At 12 months, the event-free survival rate was 83% (two deaths, one Q-wave and three non-Q-wave myocardial infarctions, four bypass surgery and 17 target lesion revascularizations), while 87% of the patients were free of angina pectoris. CONCLUSION: the outcome of the FINESS-II trial is comparable to those observed in previous stent trials (Benestent II), indicating that the coronary NIR stent is safe and effective as a primary device for the treatment of native coronary artery lesions in patients with (un)stable angina pectoris.     

Efficiency of endovascular re-interventions for evolving restenosis of different types of stents

The paper compares the results of different treatment options (balloon angioplasty and restenting) for in-stent restenosis in case of evolving restenosis of drug- and nondrug eluting stents. The investigation enrolled 496 coronary heart disease patients with clinical presentation of angina pectoris and/or signs of myocardial ischemia, as well as hemodynamic restenosis of a previously implanted stent. Of them, 216 and 280 patients had restenosis of previously implanted drug- and nondrug-eluting stents, respectively. In the patients with non-drug-eluting stent restenosis, recurrent angina pectoris and the frequency of repeated restenosis were significantly more frequently observed after balloon dilatation than after drug-eluting stent implantation (28.4 and 10.2%; p < 0.05; 19.9 and 8.7%; p < 0.05). In those with drug-eluting stent restenosis, recurrent angina pectoris and the frequency of repeated restenosis did not differ significantly between balloon dilatation of restenosis and implantation of a second drug-eluting stent.     

Multicenter evaluation of the phosphorylcholine-coated biodivYsio stent in short de novo coronary lesions: The SOPHOS study

AIMS: The BiodivYsio trade mark stent (Biocompatibles Ltd, Farnham, UK) is coated with a phosphorylcholine (PC)-containing copolymer to confer biocompatibility. The SOPHOS (Study Of PHosphorylcholine coating On Stents) study was designed to assess the safety and efficacy of this novel coronary stent and by indirect comparison to indicate equivalence with other formal stent studies. METHODS AND RESULTS: Patients with angina and a single short (#x2A7F;12 mm) de novo lesion in a native coronary artery of >/=2.75 mm diameter were included. A total of 425 patients were allocated in 24 centers. Clinical data were collected at one-, six- and nine-month follow-up. Angiography was performed before and after the stent implantation. In addition, in the first 200 patients (SOPHOS A) angiography was routinely performed at six months. The following 225 patients (SOPHOS B) were merely followed up clinically. The primary end-point of the study, the six-month MACE-rate (MACE = Major Adverse Cardiac Events) was 13.4% (two cardiac death; five Q-wave/nine non-Q-wave myocardial infarctions (MI); nine CABG and 32 target lesion revascularization (TLR), which is similar to the calculated 15% MACE-rate in comparable reference studies. Secondary end-points included among others restenosis at six months in the SOPHOS A population. The target vessel diameter was 2.98 +/- 0.48 mm. Minimal lumen diameter pre/post procedure and at follow-up was 1.00 +/- 0.32, 2.69 +/- 0.37, 1.91 +/- 0.71 mm, respectively. The binary restenosis rate (>/=50% diameter stenosis at follow-up) was 17.7%. CONCLUSION: The coronary BiodivYsio stent is safe and effective as a primary device for the treatment of native coronary artery lesions in patients with stable or unstable angina pectoris. Clinical and angiographic results are in the statistical range of equivalence with comparable studies with other current stents.     

Long period of balloon inflation and the implantation of stents potentiate smooth muscle cell death. Possible role of chronic vascular injury in restenosis

BACKGROUND: It has been suggested that the severity of acute vascular injury immediately after percutaneous transluminal coronary angioplasty (PTCA) or stent implantation correlates with the extent of neointimal hyperplasia and restenosis. However, the influence of prolonged or chronic vessel injury on the pathogenesis of restenosis is unclear. METHODS: Rabbit iliac arteries were balloon dilated for a short (1 min) or prolonged (10 min) period of time, or were chronically dilated and received a Palmaz-Schatz stent (balloon inflation for 1 min). All arteries were overexpanded to a balloon:artery ratio of 1.2:1 as determined by angiography. The arteries were removed 30 min and 4 weeks after the angioplasty procedures. The sites of injury were evaluated by gross histology and transmission electron microscopy (TEM). Cell death of medial smooth muscle cells (SMCs) was specified by TEM images 30 min after the procedures. Computer-assisted quantification of the neointimal cross-sectional areas was performed after 4 weeks using a light microscope connected to a digital image analyser. RESULTS: The results show that prolonged balloon dilatation and stent implantation increased necrotic SMC death compared with balloon dilatation for 1 min. After 30 min, increased staining of SMC nuclei, enlarged intercellular spaces and changes in SMC shape in the media indicated cell death induced by prolonged balloon dilatation or chronic stent injury. Stent implantation markedly augmented vessel damage by persistent compression of the media, compared with a balloon dilatation for 1 or 10 min. Both prolonged balloon dilatation and stent implantation increased neointimal hyperplasia at 4 weeks compared with balloon dilatation for 1 min (0.6 3 0.2 and 1.0 3 0.2 mm(2) versus 0.2 3 0.1 mm(2), P < 0.001 versus dilatation for 1 min). CONCLUSION: Prolonged or chronic vascular expansion due to long balloon-inflation periods or the implantation of stents increases medial SMC death, which subsequently stimulates neointimal growth in this restenosis model. Chronic vascular injury may be an important stimulus for restenosis after angioplasty procedures.     

Cardiovascular and splenic responses to exercise in humans.

To investigate splenic erythrocyte volume after exercise and the effect on hematocrit- and hemoglobin-based plasma volume equations, nine men cycled at an intensity of 60% maximal O(2) uptake for 5-, 10-, or 15-min duration, followed by an incremental ride to exhaustion. The reduction in spleen volume, calculated using (99m)Tc-labeled erythrocytes, was not significantly different among the three submaximal rides (5 min = 28%, 10 min = 30%, 15 min = 36%; P = 0.26). The incremental ride to exhaustion resulted in a 56% reduction in spleen volume, which recovered to baseline levels within 20 min. Plasma catecholamines were inversely related to spleen volume after exercise (r = 0.70-0.84; P < 0.0001). There were no differences in red cell or total blood volume pre- to postexercise; however, a significant reduction in plasma volume was observed (18.9%; P < 0.01). There was no difference between the iodinated albumin and the hematocrit and hemoglobin methods of assessing plasma volume changes. These results suggest that the spleen regulates its volume in response to an intensity-dependent signal, and plasma catecholamines appear partially responsible. Splenic release of erythrocytes has no effect on indirect measures of plasma volume.