Decrease In Lumen Diameter Research Articles

Comprehensive Analysis of Post-Pipeline Endothelialization and Remodeling.

Successful post-flow-diverter endoluminal reconstruction is widely believed to require endothelial overgrowth of the aneurysmal inflow zone. However, endothelialization/neointimal overgrowth is a complex process, over which we currently have very limited influence. Less emphasized is vascular remodeling of the target arterial segment, the dynamic response of the vessel to flow-diverter implantation. This process is distinct from flow modifications in covered branches. It appears that basic angiographic methods allow simple and useful observations. The purpose of this article was to quantitatively evaluate observable postimplantation changes in target vessels following deployment of Pipeline endoluminal constructs. One hundred consecutive adults with unruptured, previously untreated, nondissecting aneurysms treated with the Pipeline Embolization Device with Shield Technology and the availability of follow-up conventional angiography were studied with 2D DSA imaging. Target vessel size; Pipeline Embolization Device diameter; endothelial thickness; and various demographic, antiplatelet, and device-related parameters were recorded and analyzed. The thickness of neointimal overgrowth (mean, 0.3 [SD, 0.1] mm; range, 0.1-0.7 mm) is inversely correlated with age and is independent of vessel size, smoking status, sex, and degree of platelet inhibition. The decrease in lumen diameter caused by neointimal overgrowth, however, appears counteracted by outward remodeling (dilation) of the target arterial segment. This leads to an increase in the diameter with a corresponding decrease in length (foreshortening) of the implanted Pipeline Embolization Device. This physiologic remodeling process affects optimally implanted devices and is not a consequence of stretching, device migration, vasospasm, and so forth. A direct, linear, statistically significant relationship exists between the degree of observed outward remodeling and the diameter of the implanted Pipeline Embolization Device relative to the target vessel. Overall, remodeled arterial diameters were reduced by 15% (SD, 10%) relative to baseline and followed a normal distribution. Clinically relevant stenosis was not observed. Vessel healing involves both outward remodeling and neointimal overgrowth. Judicial oversizing could be useful in specific settings to counter the reduction in lumen diameter due to postimplant neointimal overgrowth; however, this overszing needs to be balanced against the decrease in metal coverage accompanying the use of oversized devices. Similar analysis for other devices is essential.

Distinct Temporal Pattern of the Prediction of Lumen Remodeling of Lower Extremity Vein Bypass Grafts by Initial Local Hemodynamics.

We predicted human lower extremity vein bypass graft remodeling by hemodynamics. Computed tomography and duplex ultrasound scans of 55 patients were performed at 1week and 1, 6, and 12months post-implantation to obtain wall shear stress (WSS) and oscillatory shear index (OSI) at 1-mm intervals via computational fluid dynamics simulations. Graft remodeling was quantified by computed tomography-measured lumen diameter changes in the early (1week-1month), intermediate (1-6months), and late (6-12months) periods. Linear mixed-effect models were constructed to examine the overall relationship between remodeling and initial hemodynamics using the average data of all cross sections within the same graft. A significant association of graft remodeling with WSS (p < 0.001) and time (p = 0.001) was found; however, the effect size decreased with time (every 2.7 dyne/cm2 increase of WSS was associated with a 0.39, 0.35, 0.002mm diameter increase in the three periods, respectively). The association of remodeling with OSI was significant only in the intermediate period (every 0.1 increase of OSI was associated with a 0.25mm lumen diameter decrease, p = 0.004). Therefore, the association of graft lumen remodeling with local hemodynamics has a distinct temporal pattern; WSS and OSI are predictive of remodeling only in certain postoperative periods.

CLINICAL EXAMINATION OF THE MENTAL AND SOMATIC HEALTH OF CHILDREN AND ADOLESCENTS FROM DISADVANTAGED FAMILIES

In order to study the structural features of the cerebral cortex vessels a model of acute inflammation was created by intravenous administration of purified lipopolysaccharide (1 mg/kg) to white rats. Cryostat sections as well as semi and ultrathin sections of brain cortex were studied by means of light and electron microscopy. In experimental animals there was a decrease in lumen diameter of the arteries located in subarachnoid and subpial spaces, the expansion of the perivascular spaces around the cortical arterioles, signs of disturbances in blood-brain barrier integrity in the wall of microcirculation vessels.

Comparison Of Endothelial-dependent Vasodilatory And Vasoconstrictor Responses Between Upper- And Lower-Limb Arteries In Older Adults

Low-flow mediated constriction (L-FMC) provides important information about the acute effects of reduced shear stress on endothelial function. L-FMC has been mainly tested in upper-limb arteries, where an inverse association with VO2peak has been observed in younger adults. It is unclear if an L-FMC response exists in lower limb arteries, which are exposed to larger fluctuations in shear stress during traditional modes of aerobic exercise than the upper-limb. Furthermore, it is uncertain whether the same inverse relationship between L-FMC and VO2peak exists in older adults (OA). PURPOSE: Based on known differences in flow-mediated dilation (FMD) between upper- and lower limbs, we tested the hypothesis that heterogeneous L-FMC responses exist between the brachial- (BA) vs. popliteal (POP) arteries. We also expected that OA with greater aerobic fitness would have larger L-FMC responses in both arteries. METHODS: FMD and L-FMC were assessed in 47 OA (67±5 yr; 30F) using high-resolution duplex ultrasonography with commercial edge-detection and wall-tracking software. L-FMC was defined as the % decrease in lumen diameter in response to 5-min of distal ischemia. FMD was calculated as the % increase in lumen diameter following a reactive hyperemia. RESULTS: Larger FMD responses were observed in the BA vs. POP (4.7±1.6% vs. 3.3±2.0%; P<0.001), which were moderately correlated to each other (r=0.54; P<0.001). When allometrically scaled, the BA exhibited a greater L-FMC response than the POP (-1.3±1.6% vs. -0.4±1.6%; P=0.03). L-FMC responses in the BA vs. POP were not correlated with each other (r=0.22; P=0.14). As expected, VO2peak was associated with both BA-FMD (r=0.59; P<0.001) and POP-FMD (r=0.48; P=0.001). VO2peak was moderately correlated to BA L-FMC (r=-0.52; P<0.001) but strongly correlated to POP L-FMC (r=-0.73; P<0.001). CONCLUSION: The heterogeneous L-FMC responses between the BA and POP indicates that upper limb L-FMC responses do not represent a systemic measure of vasoconstrictor capacity. The stronger association between VO2peak and POP L-FMC suggests that larger local shear stress responses, induced by traditional lower-limb modes of aerobic exercise, may result in greater adaptations to low flow-mediated endothelial vasoconstrictor responsiveness.

Abstract 222: Exercise Training Prevents Rarefaction of Pial Collaterals, Promotes Cerebral Arterial Remodeling, and Lessens Severity of Stroke in Aging Brain

Variation in anatomic extent of the collateral circulation is an important determinant of variation in the severity of ischemic stroke and efficacy of revascularization therapies. Yet pial collateral number and lumen diameter decrease with age, at least in mice. It is not known if this can be mitigated. We tested whether exercise training can accomplish this and if it also affects diameter of the posterior communicating collalterals (PComs) and primary cerebral arteries (ICA, BA, MCA, ACA, PCA). We randomized 30 male and 30 female, 12 months-old (~40 human years, hy) C57BL/6J mice to either sedentary or voluntary wheel-running (daily distance run was measured). At 25 mos-age (~70 hy), permanent MCA occlusion was followed 24h later by vascular casting after maximal dilation and by determination of infarct volume. Controls for aging were 3 mos-old sedentary mice (~16 hy). Training effect was confirmed by muscle fiber-type switching, body weight and cardiac hypertrophy (all p&lt;0.05). Exercise prevented age-associated loss of collateral number and diameter (p=0.049 and 0.005, n=13-14) and reduced infarct volume by 50%, ie, to that seen in 3 months-old mice (p=0.01, n=7). Unlike pial collaterals, PCom diameter and number (ie, present bilaterally, unilaterally or absent) were unaffected by exercise. Of further interest, diameter of the primary cerebral arteries increased with aging alone (119 ± 1 vs 134 ± 5 μm averaged combined diameter, p=0.02, n=10-14); this effect tended to increase further with exercise (143 ± 4 μm, p=0.07, n=13). Mechanistically, exercise increased vascular expression (assessed by immunohisto-chemistry) of total eNOS (p=0.03, n=5-6), phospho-eNOS (p=0.004, n=5) and a marker of anti-oxidative stress (SOD, p=0.008, n=5-6; but not HO-1, p=0.40, n=6). It did not alter a marker of aging (p16, p=0.42, n=5); analysis of additional targets is underway. In conclusion, exercise training prevented age-induced rarefaction of pial collaterals and reduced infarct volume. In addition and unexpectedly, aging also caused outward remodeling of the primary cerebral arteries, and exercise training tended to further augment this. These benefits of regular aerobic exercise were associated with increased eNOS bioavailability and reduced oxidative stress.

Increased Notch3 Activity Mediates Pathological Changes in Structure of Cerebral Arteries.

CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), the most frequent genetic cause of stroke and vascular dementia, is caused by highly stereotyped mutations in the NOTCH3 receptor, which is predominantly expressed in vascular smooth muscle. The well-established TgNotch3R169C mouse model develops characteristic features of the human disease, with deposition of NOTCH3 and other proteins, including TIMP3 (tissue inhibitor of metalloproteinase 3), on brain vessels, as well as reduced maximal dilation, and attenuated myogenic tone of cerebral arteries, but without elevated blood pressure. Increased TIMP3 levels were recently shown to be a major determinant of altered myogenic tone. In this study, we investigated the contribution of TIMP3 and Notch3 signaling to the impairment of maximal vasodilator capacity caused by the archetypal R169C mutation. Maximally dilated cerebral arteries in TgNotch3R169C mice exhibited a decrease in lumen diameter over a range of physiological pressures that occurred before myogenic tone deficits. This defect was not prevented by genetic reduction of TIMP3 in TgNotch3R169C mice and was not observed in mice overexpressing TIMP3. Knock-in mice with the R169C mutation (Notch3R170C/R170C) exhibited similar reductions in arterial lumen, and both TgNotch3R169C and Notch3R170C/R170C mice showed increased cerebral artery expression of Notch3 target genes. Reduced maximal vasodilation was prevented by conditional reduction of Notch activity in smooth muscle of TgNotch3R169C mice and mimicked by conditional activation of Notch3 in smooth muscle, an effect that was blood pressure-independent. We conclude that increased Notch3 activity mediates reduction in maximal dilator capacity of cerebral arteries in CADASIL and may contribute to reductions in cerebral blood flow.

Effect of Perflubron-induced lung growth on pulmonary vascular remodeling in congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) involves lung hypoplasia and pulmonary hypertension (PH). Post-natal Perflubron ventilation induces lung growth. This phenomenon is called Perflubon-induced lung growth (PILG). However, it does not appear to ameliorate PH in CDH. We aim to determine the effect of PILG on pulmonary vascular remodeling in neonates with CDH and PH requiring extracorporeal membrane oxygenation (ECMO). Lung tissue from four patients was obtained, three treated with PILG+ECMO, and one maintained on conventional ventilation+ECMO (control). The distribution of collagen was assessed with Masson's trichrome stain. Immunohistochemistry was done to assess cell proliferation and immunofluorescence to assess vascular morphology. Comparing PILG vs. control, there was an increase in vessel wall diameter (6.85μm, 10.28μm, and 10.35μm vs. 4.34μm), increase in collagen thickness in two PILG patients (35.66μm, 14.23μm, and 38.46μm vs. 22.16μm), and decrease in lumen diameter despite similar total area (48.99μm, 41.74μm, and 36.32μm vs. 51.56μm) for each PILG patient vs. the control patient, respectively. PILG does not appear to improve pulmonary vascular remodeling that occurs with PH. The findings are descriptive and will require larger samples to validate the significance of the findings. Overall, further studies will be required to identify the mechanistic causes of PH in CDH to create effective treatments.

Plasma homocysteine levels are related to medium-term venous graft degeneration in coronary artery bypass graft patients.

Objective:Saphenous venous grafts (SVGs) are established choices for coronary artery bypass grafting (CABG); however, their lumen patency is limited. Our goal was to investigate the risk factors of SVG degeneration.Methods:Seventy-five patients (mean age, 57.5±10.4 years) with 133 SVG conduits who had cardiac catheterization ≥1 year after CABG were selected; follow-up period was 67.6±36.8 months. Patients were divided into 3 groups according to angiographic status at follow up [intact: <20% (n=23); narrowed: 20–99% (n=24); and occluded (n=28)]. Baseline clinical conditions were evaluated in relation to follow-up angiography. As onset date of chronic total occlusions is usually uncertain, they arise typically from thrombotic lesions; thus, their value in evaluation is limited.Results:There were no significant differences between the 3 groups in clinical parameters. Linear correlation analysis found significant (p<0.01) positive connection of SVG disease (luminal diameter reduction 20–99%) with C-reactive protein (CRP) and homocysteine (Hcy), as well as between CRP and Hcy. Multiple regression analysis showed plasma Hcy level to be significantly related to graft diameter reduction normalized to time elapsed until angiography in narrowed grafts: 1 µmol/L increase of Hcy was associated with 0.053%/month decrease in lumen diameter (p<0.01; R2=0.428); extrapolating: +10 µmol/L higher Hcy level during 5 years is associated with 32.1% lumen reduction.Conclusion:Medium- to long-term SVG degeneration is related to elevated plasma total Hcy in patients with sub-occlusive graft stenosis, while in cases with intact SVGs, the beneficial local flow conditions may protect the grafts from degeneration.

The eff ect of intracoronary administration of ergonovine on the contralateral coronary artery in a provocation test for the diagnosis of variant angina

Background Little is known about the effects of selective intracoronary administration of ergonovine into a coronary artery on the artery on the other side. This study aimed to evaluate the effect of intracoronarily administered ergonovine on the contralateral coronary artery.Subjects and methods From June 2011 to August 2013, coronary spasm provocation tests were performed in 85 consecutive patients using selective intracoronary administration of methylergometrine maleate (ER). The doses increased in a step-wise manner up to 60 μg for the left coronary artery (LCA) and up to 50 μg for the right coronary artery (RCA). The coronary artery diameters were measured and analysed by repeated-measures ANOVA.Results Twenty-four (28%) patients had a spasm-positive result. The mean diameter of the spasm segment in the contralateral artery decreased from 2.83 to 2.68 mm (5.1 ± 0.1% change, P< 0.001) in the negative spasm group and from 2.40 to 2.10 mm (11.1 ± 2.2% change, P= 0.001) in the positive spasm group. There were no serious procedure-related complications.Conclusions Intracoronary administration of ER resulted in a statistically significant decrease of lumen diameter of the contralateral coronary artery. However, from the clinical perspective, the extent of the decrease was relatively small and the test may be conducted safely unless there is a significant coronary artery luminal narrowing.

The actomyosin machinery is required for Drosophila retinal lumen formation.

Multicellular tubes consist of polarized cells wrapped around a central lumen and are essential structures underlying many developmental and physiological functions. In Drosophila compound eyes, each ommatidium forms a luminal matrix, the inter-rhabdomeral space, to shape and separate the key phototransduction organelles, the rhabdomeres, for proper visual perception. In an enhancer screen to define mechanisms of retina lumen formation, we identified Actin5C as a key molecule. Our results demonstrate that the disruption of lumen formation upon the reduction of Actin5C is not linked to any discernible defect in microvillus formation, the rhabdomere terminal web (RTW), or the overall morphogenesis and basal extension of the rhabdomere. Second, the failure of proper lumen formation is not the result of previously identified processes of retinal lumen formation: Prominin localization, expansion of the apical membrane, or secretion of the luminal matrix. Rather, the phenotype observed with Actin5C is phenocopied upon the decrease of the individual components of non-muscle myosin II (MyoII) and its upstream activators. In photoreceptor cells MyoII localizes to the base of the rhabdomeres, overlapping with the actin filaments of the RTW. Consistent with the well-established roll of actomyosin-mediated cellular contraction, reduction of MyoII results in reduced distance between apical membranes as measured by a decrease in lumen diameter. Together, our results indicate the actomyosin machinery coordinates with the localization of apical membrane components and the secretion of an extracellular matrix to overcome apical membrane adhesion to initiate and expand the retinal lumen.

Aortic remodelling in chronic nicotine-administered rat.

Vascular remodelling is an adaptive mechanism, which counteracts pressure changes in blood circulation. Nicotine content in cigarette increases the risk of hypertension. The exact relationship between nicotine and vascular remodelling still remain unknown. Current study was aimed to determine the effect of clinically relevant dosage of nicotine (equivalent to light smoker) on aortic reactivity, oxidative stress markers and histomorphological changes. Twelve age-matched male Sprague-Dawley rats were randomly divided into two groups, i.e.: normal saline as control or 0.6 mg/kg nicotine for 28 days (i.p., n=6 per group). On day-29, the rats were sacrificed and the thoracic aorta was dissected immediately for further studies. Mean arterial pressure (MAP) and pulse pressure (PP) of nicotine-treated vs. control were significantly increased (p<0.05). Nicotine-treated group showed significant (p<0.05) increase tunica media thickness, and decrease in lumen diameter, suggesting vascular remodelling which lead to prior hypertension state. The phenylephrine (PE)-induced contractile response in nicotine group was significantly higher than control group (ED50=1.44×105 M vs. 4.9×106 M) (p<0.05~0.001). However, nicotine-treated rat showed significantly lower endothelium-dependent relaxation response to acetylcholine (ACh) than in control group (ED50=6.17×107 M vs. 2.82×107 M) (p<0.05), indicating loss of primary vascular function. Malondialdehyde (MDA), a lipid peroxidation marker was significantly higher in nicotine group. Superoxide dismutase (SOD) enzymatic activity and glutathione (GSH) were all reduced in nicotine group (p<0.05) vs. control, suggesting nicotine induces oxidative imbalance. In short, chronic nicotine administration impaired aortic reactivity, probably via redox imbalance and vascular remodelling mechanism.

Morphological and functional evaluation of the bioresorption of the bioresorbable everolimus-eluting vascular scaffold using IVUS, echogenicity and vasomotion testing at two year follow-up: a patient level insight into the ABSORB A clinical trial

The aim of this study was to describe vaso-reactivity (by Acetylcholine and Methergine tests) at 2 year follow-up in parallel with the individual changes in the echogenicity characteristics of the polymer struts of the everolimus eluting bioresorbable vascular scaffold (BVS), from post-treatment to 2 year follow-up, in patients enrolled in the ABSORB Cohort A study. Intravascular ultrasound assessment was performed with a phased array catheter (EagleEye, Volcano Corporation, Cordova, CA, USA) with automated pullback at 0.5 mm per second. The % ratio at 6 months and 2 years [(Scaffold Area post PCI- Lumen Area)/Scaffold Area post PCI] was calculated as a measure of scaffold shrinkage. The % change of hyperechogenicity was defined as: ([post-procedural hyperechogenicity] - [2 year follow up hyperechogenicity])/[post-procedural hyperechogenicity]) × 100. The vasomotion test with intracoronary acetylcholine (10(-6) M) or intravenous methergine (0.4 mg) was performed at 2 years. Overall nine patients received all these analyses and were enrolled in the present analysis. A 50-96% reduction in hyperechogenicity was observed between baseline and 2 years, which corresponded to a change in vasoreactivity between 2 and 22%. A vasoconstriction of the scaffolded segment was observed in the 5 patients, who underwent the methergine test, with a mean decrease in lumen diameter after methergine of 9 ± 7% (P = 0.06), while vasodilatation occurred in the 4 patients who underwent the acetylcholine test with a mean increase in lumen diameter after acetylcholine of 8 ± 5% (P = 0.125). Bioresorption of the BVS is accompanied by re-establishment of both endothelial and non-endothelial dependent vasomotion.

Pleiotropic Effect of Lovastatin, With and Without Cholestyramine, in the Post Coronary Artery Bypass Graft (Post CABG) Trial

This study evaluated patients in the Post Coronary Artery Bypass Graft (Post CABG) trial for evidence of statin pleiotropic effects in preventing atherosclerotic progression in saphenous vein grafts (SVGs). We studied 1,116 of the 1,351 patients in the Post CABG trial who were randomized to aggressive (low-density lipoprotein [LDL] cholesterol target <85 mg/dl) or moderate (target LDL cholesterol <140 mg/dl) lovastatin treatment and who had sufficient data available. The generalized estimating equation models, adjusting for important covariates, were applied to estimate the odds ratios (ORs) and probability of substantial atherosclerotic SVG progression (decrease in lumen diameter >or=0.6 mm) and the difference in minimum lumen diameter change between treatment groups. Aggressive lovastatin treatment compared with moderate treatment was associated with a significant decrease in risk of significant SVG atherosclerotic progression after adjustment for baseline cholesterol level, LDL cholesterol on treatment, high-density lipoprotein cholesterol, and triglyceride changes on treatment and other independent predictors (OR 0.68, 95% confidence interval 0.49 to 0.94, p = 0.019). Results were similar when the change or percent change from baseline of LDL cholesterol level on treatment was adjusted for rather than on-treatment LDL cholesterol and in the subset achieving a year-1 LDL cholesterol level from 90 to 135 mg/dl (OR 0.64, 95% confidence interval 0.42 to 0.98, p = 0.042). Mean decrease in minimum lumen diameter was also significantly smaller in the aggressive than the moderate treatment arm (-0.256 vs -0.343 mm, p = 0.042). In conclusion, aggressive versus moderate lovastatin treatment appeared therapeutic in slowing the atherosclerotic process in SVGs from Post CABG patients, independent of its greater LDL cholesterol-lowering effect.

Systemic Antiphospholipid Syndrome and Atherosclerosis

Atherosclerosis (AT) is a metabolic, systemic inflammatory/immune disease characterized by lipoproteins metabolism alteration that leads to immune/inflammatory system activation with the consequent proliferation of smooth-muscle cells, narrowing arteries and atheroma formation. Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombophilic state and circulating antiphospholipid antibodies (aPL) including anti beta2-GPI. Experimental studies and human observations suggest that APS is associated with AT. In fact, innate and adaptive immune responses participate in the pathogenesis of both diseases. Anti-oxLDL, anti-aPL, anti beta2GPI, anti-HSP antibodies, among others, has been found in patients with APS and AT. Endothelial dysfunctions, oxidative stress, increase of cell adhesion molecules, active platelets, are common findings in both diseases. Macrophages, dendritic cells, T-cell activation, CD40-CD40 ligand interaction, are considered as pathogenic mechanism of AT and APS. Premature AT may be the first symptom of APS. Thrombophilia, aPL antibodies, and APS may be present in patients with premature AT. An association between AT and venous thrombosis (a clinical hallmark of APS) has been proposed in unselected patients with deep venous thrombosis of the legs without symptomatic AT. Asymptomatic AT, defined in terms of carotid intima media thickness and lumen diameter decrease, was observed in patients with APS. Premenopausal female patients with PAPS have a higher prevalence of cerebrovascular disease in comparison with male patients. Accelerated AT and hormones could be the explanation of these findings. High levels of aCLs, significantly predict the risk of future ischemic stroke in women but not in men. AT is one of the main features of systemic APS and offer opportunities for new treatment strategies.

Candesartan- and Atenolol-Based Treatments Induce Different Patterns of Carotid Artery and Left Ventricular Remodeling in Hypertension

Angiotensin receptor blocker (ARB)-based treatment reduces cardiovascular events and stroke more than does beta-blocker-based treatment despite similar blood pressure (BP) reduction. We investigated whether these treatments have different effects on cardiac and large-artery remodelling and evaluated the relation of arterial remodelling to hemodynamic changes in subjects with hypertension. We compared the treatment effects of an ARB (candesartan cilexetil)-based regimen and a beta-blocker (atenolol)-based regimen for 52 weeks on common carotid artery (CCA) and left ventricular structure in hypertensive patients in a randomized, double-blind study. Clinic brachial BP and 24-hour ambulatory BP, carotid BP, left ventricular mass index, CCA intima-media thickness, lumen diameter, intima-media area, and carotid blood flow were measured. Distensibility, circumferential tensile stress, Young's elastic modulus (E(m)), and shear stress (tau) in the CCA were also calculated. Both candesartan and atenolol reduced intima-media thickness and intima-media area and increased distensibility to similar extents after 52 weeks of treatment. Despite similar reductions in BP, treatment with atenolol resulted in a lesser reduction in left ventricular mass index, a decrease in lumen diameter, and a reduction in carotid blood flow compared with candesartan. BP-independent effects of ARB on cardiac and arterial structure may contribute to the beneficial effects of these agents on cardiovascular disease.

C-Reactive Protein, Clinical Outcome, and Restenosis Rates After Implantation of Different Drug-Eluting Stents

Sirolimus-eluting stents (SESs), paclitaxel-eluting stents (PESs), and dexamethasone-eluting stents (DEXs) have anti-inflammatory properties; thus, the decreased in-segment restenosis rate observed with the use of these stents might be related to a weaker postprocedural inflammatory response. One hundred sixty consecutive patients with stable coronary artery disease who underwent successful single-vessel/lesion coronary artery stenting were prospectively studied. Thin-strut bare metal stents were deployed in 39 patients, SESs in 30, PESs in 61, and DEXs in 30. The 4 groups were similar with respect to demographic and angiographic variables and prevalence of risk factors. C-reactive protein (CRP) was measured at baseline and 24 and 48 hours after the procedure. Maximal increase in CRP was calculated as the increase in CRP at 48 hours/CRP compared with baseline. Angiographic follow-up was performed after 12.9 +/- 1.3 months or sooner, if needed, on the basis of clinical evidence. All patients presented a postprocedural increase in CRP that peaked at 48 hours (median 10.0 mg/L). Maximal CRP increase was similar across the 4 groups (medians 3.5 mg/L in the bare metal stent group, 3.6 mg/L in the SES group, 4.0 mg/L in the PES group, 3.5 mg/L in the DEX group, p = 0.45). Incidences of angiographic binary restenosis (>50% lumen diameter decrease) were 20.5% in the bare metal stent group, 3.3% in the SES group, 4.9% in the PES group, and 36.6% in the DEX group (p = 0.0004 for SES and PES groups vs bare metal stent and DEX groups). Postprocedural increase in CRP was significantly correlated with clinical and angiographic outcomes. In conclusion, the acute postprocedural systemic inflammatory response induced by drug-eluting stent implantation appears to be similar to that induced by bare metal stents. However, the restenosis rate is lower for SESs and PESs than for DEXs and bare metal stents. Thus, the decreased incidence of stent restenosis that was observed after SES and PES deployment is unlikely to be related to a decreased acute systemic inflammatory response, but rather to an increased local resistance to inflammatory mediators.

Airway narrowing in porcine bronchi with and without lung parenchyma

During bronchoconstriction elastic after-loads arise due to distortion of lung parenchyma by the narrowing airway. In the present study, the functional effect of parenchymal elastic after-load on airway narrowing was determined. Airway narrowing was measured in vivo over a range of transpulmonary pressures and compared with in vitro narrowing measured at corresponding transmural pressures. Bronchi were generation 10 with internal diameters of approximately 4 mm. In vivo luminal narrowing was measured by videobronchoscopy in anaesthetised and ventilated pigs. In vitro luminal narrowing was measured by videoendoscopy in isolated bronchial segments. Airways were activated by maximum vagal nerve stimulation and maximum electrical field stimulation in vivo and in vitro, respectively. At 5 cmH2O, stimulation produced a 35.9+/-3.2% (n = 6) and a 36.5+/-2.4% (n = 11) decrease in lumen diameter in vivo and in vitro, respectively. At 30 cmH2O, luminal narrowing fell to 23.7+/-2.0% in vivo and 23.4+/-2.5% in vitro. There was no difference between luminal narrowing in vivo and in vitro at any pressure. In conclusion, these findings suggest that in mid-sized, cartilaginous bronchi, parenchymal elastic after-loads do not restrict airway narrowing.

Reductions in Basal Limb Blood Flow and Lumen Diameter after Short-Term Leg Casting

We tested the hypotheses that short-term casting immobilization of a leg would reduce basal blood flow and vascular conductance and induces structural alterations in femoral artery. Right knee and ankle joints of eight healthy young men were immobilized with casting for 7 d. Before and immediately after casting, and 14 d after the cast was removed, femoral artery hemodynamics and structure were measured using a high-resolution ultrasound. Femoral artery lumen diameter in the immobilized leg decreased after the immobilization (P < 0.05) and returned to baseline during the recovery period, in which the subjects did not receive any special rehabilitation treatment. Femoral artery intima-media thickness (IMT) and IMT/lumen ratio in both legs did not show significant changes throughout the interventions. In the immobilized leg, femoral artery blood flow and vascular conductance decreased (-23 to 24%) after the immobilization (all P < 0.05). These parameters returned to the baseline during the recovery period, and there were no significant differences between the baseline and recovery values. In the control leg, femoral blood flow and vascular conductance did not change throughout the investigation. After 7 d of casting, femoral arterial distension, an index of arterial distensibility, tended to decrease in the immobilized leg but not in the control leg. We concluded that a short-term immobilization of lower limb decreases basal limb blood flow and arterial lumen diameter. These results suggest that basal limb blood flow and lumen diameter decrease rapidly upon the cessation of muscular weight bearing and locomotor activity, and may be modulated by an ordinary level of physical activity.

Molecular and cellular basis of pulmonary vascular remodeling in pulmonary hypertension

Clinical pulmonary hypertension is characterized by a sustained elevation in pulmonary arterial pressure. Pulmonary vascular remodeling involves structural changes in the normal architecture of the walls of pulmonary arteries. The process of vascular remodeling can occur as a primary response to injury, or stimulus such as hypoxia, within the resistance vessels of the lung. Alternatively, the changes seen in more proximal vessels may arise secondary to a sustained increase in intravascular pressure. To withstand the chronic increase in intraluminal pressure, the vessel wall becomes thickened and stronger. This “armouring” of the vessel wall with extra-smooth muscle and extracellular matrix leads to a decrease in lumen diameter and reduced capacity for vasodilatation. This maladaptive response results in increased pulmonary vascular resistance and consequently, sustained pulmonary hypertension. The process of pulmonary vascular remodeling involves all layers of the vessel wall and is complicated by the finding that cellular heterogeneity exists within the traditional compartments of the vascular wall: intima, media, and adventitia. In addition, the developmental stage of the organism greatly modifies the response of the pulmonary circulation to injury. This review focuses on the latest advances in our knowledge of these processes as they relate to specific forms of pulmonary hypertension and particularly in the light of recent genetic studies that have identified specific pathways involved in the pathogenesis of severe pulmonary hypertension. Copyright 2002, Elsevier Science (USA). All rights reserved.

Compensatory enlargement and stenosis develop in apoE(-/-) and apoE*3-Leiden transgenic mice.

Atherosclerotic mouse models develop little ischemic organ damage and no infarctions, despite the presence of large atherosclerotic lesions. Therefore, we hypothesize that luminal changes do not follow atherosclerotic lesion development. Because a phenomenon that may explain the discrepancy between luminal changes and lesion size is vascular remodeling, we measured parameters of vascular remodeling in the carotid arteries (CAs), thoracic aorta (TA), and abdominal aorta (AA) of apolipoprotein E (apoE)-deficient (apoE(-/-)) and apoE*3-Leiden mice, 2 well-known mouse models of atherosclerosis. Atherosclerotic lesions were classified (American Heart Association [AHA] types II through V), and plaque thickness, compensatory enlargement versus constrictive remodeling, lumen diameter, stenosis, and media thickness were measured relative to the nondiseased arterial wall. In CAs, plaque thickness increased during atherogenesis. CAs showed compensatory enlargement (apoE(-/-) 55%, apoE*3-Leiden 38%). Regression analysis revealed a positive correlation between plaque and lumen area (for apoE(-/-), R=0.95; for apoE*3-Leiden, R=0.90). Medial thinning and elastolysis were also observed. During atherogenesis, lumen diameter decreased (apoE(-/-) -69%, apoE*3-Leiden -40%), and stenosis >70% developed. TA and AA showed similar features, but neither developed a progressive decrease in lumen diameter or stenosis >70%. In CAs, TA, and AA of apoE(-/-) and apoE*3-Leiden mice, atherogenesis is associated with compensatory enlargement, medial thinning, and elastolysis. A progressive decrease in lumen diameter and stenoses >70% occur only in CAs. Vascular remodeling is more prominent in apoE(-/-) mice.