Reduction In Lumen Diameter Research Articles

An investigation on some toxic effects of pyriproxyfen in adult male mice.

Objective(s):Pyriproxyfen as an insect growth regulator is widely used globally for pest management. There are reports on adverse effects of insecticides such as organ toxicity, endocrine disruptions, and teratogenicity in animals and humans. We aimed to investigate reproductive toxicity of pyriproxyfen in adult male mice.Materials and Methods:48 male Swiss albino mice were divided into eight groups and received the different 1200, 600, 320, 200, 100, 40, 20, 0 mg/kg/day doses orally, and body weights were accessed for 28 consecutive days. In the end, mice were sacrificed, testes were dissected and weighed. Probable testicular tissue alterations were examined by histopathological studies. In addition, the diameter of seminiferous tubules and Leydig cells distribution were assessed in all experimental and control groups.Results:Pyriproxyfen treatment caused significant (P<0.05) reduction in body and organ weights in mice. However, the shrinkage and displacement of seminiferous tubules, reduced lumen diameter, and vacuolization occurred in seminiferous tubules in higher doses exposed animals in comparison to controls. The relative testis weights, mean diameter of seminiferous tubules, and Leydig cells distribution remained unchanged at low doses. Conclusion:These findings reveal that pyriproxyfen caused reduction in body weight gain as well as damage to the testicular architecture in mice and thus may potentially interfere with spermatogenesis. Findings in an outbred strain of mice can be extrapolated fairly reliably to the human model. The chemical can thus be further exploited to study its effects on impairment of fertility and as an endocrine disruptor.

Use of coronary computed tomography angiography in clinical practice - single centre experience in Switzerland in light of current recommendations based on pretest probability considerations.

Coronary computed tomography angiography (CCTA) is recommended as a first-line option for the exclusion of coronary artery disease in patients with low to intermediate (15&ndash;50%) pretest probability. We aimed to study the use of CCTA in clinical practice in a single centre in Switzerland in light of this recommendation. In 523 consecutive patients (age 56 &plusmn; 13 years, 48% females) undergoing CCTA during a period of 2 years, the pretest probability of coronary artery disease was assessed using the revised Diamond-Forrester model (CAD consortium score). In patients who had invasive coronary angiography following CCTA, angiographic findings and the consequences regarding management are reported. The majority of patients (n = 316; 60%) had a pretest probability &lt;15%, 188/523 (36%) had a pretest probability between 15 and 50%, and 19/523 (4%) had a pretest probability &gt;50%. The prevalences of coronary artery disease (&ge;50% lumen diameter reduction) by CCTA in patients with pretest probability &lt;15%, 15&ndash;50%, and &gt;50% were 25/316 (8%), 45/188 (24%) and 8/19 (42%), respectively. In 438/523 patients (84%), a CCTA scan showing no coronary artery disease represented the final diagnostic step. In patients undergoing invasive coronary angiography (n = 59, age 58 &plusmn; 9 years, 88% with coronary artery disease by CCTA), coronary artery disease was found in 47/59 (80%) patients and 36/59 (61%) patients underwent revascularisation. The prevalences of coronary artery disease by invasive coronary angiography in patients with pretest probability &lt;15%, 15&ndash;50%, and &gt;50% were 14/21 (67%), 28/32 (88%) and 5/6 (83%). The present data suggest that the currently used pretest probability model is still imperfect and that guideline recommendations regarding pretest probability use for the selection of CCTA candidates are not followed completely. Still, in more than 80% of patients coronary artery disease could be excluded by CCTA, while CCTA also detected a significant number of patients with coronary artery disease in the low pretest probability population. Thus, the data suggest a very judicious use of CCTA as a gatekeeper for invasive coronary angiography in current practice.

DEVELOPING OF A NEW RABBIT CAROTID ARTERY MODEL OF NEOINTIMAL HYPERPLASIA WITH SEVERE STENOSIS: MONITORED BY ULTRASONOGRAPHY AND HISTOPATHOLOGY

Neointimal hyperplasia is the major cause of restenosis after percutaneous coronary and carotid interventions such as stenting or angioplasty. Neointimal hyperplasia is also used to describe the thickening of venous and prosthetic bypass grafts that leads to reduced lumen diameter and flow and, ultimately, graft occlusion and thrombosis. Direct investigation of neointimal hyperplasia stenosis in human arteries is by nature difficult to do. As a result, animal models offer an alternative that can replicate the physiopathology aspects of neointimal hyperplasia stenosis while allowing for controllable variables and statistical data in a short period of time. Therefore, an appropriate animal model could prove critical to the research and development of new diagnostic and therapeutic modalities. The aim of this study was to generate an easily reproducible and inexpensive experimental rabbit common carotid artery of neointimal hyperplasia stenosis with morphological similarities to the human disease. Twenty- eight healthy male New Zealand white rabbits weighing 2.5-3.0 kg were used in this study. Rabbits were divided randomly into a healthy group (A) in which the rabbits consumed a standard chow diet (n = 14), and an injured group (B) in which the rabbits underwent perivascular cold injury to the right common carotid artery using liquid nitrogen. Histopathology results showed progressive smooth muscle cells proliferation in intimal layer, resulting in vessel wall thickening and the formation of neointimal hyperplasia with moderate artery stenosis in all of the rabbits’ arteries after four weeks. Results from color Doppler ultrasonography at the stenotic region showed a significant increase in the mean value for blood mean velocity, wall mean thickness, percentage of luminal cross- sectional area of stenosis and significant reduction in the mean value for blood volume flow in the neointimal hyperplasia group compared with the control group (p < 0.05). In conclusion, we successfully produced an easily reproducible and inexpensive experimental rabbit common carotid artery model of neointimal hyperplasia stenosis, which is similar to the condition seen in patients. This condition in rabbits can be properly assessed by color Doppler ultrasonography.

Intravascular ultrasound assisted sizing in thoracic endovascular aortic repair improves aortic remodeling in Type B aortic dissection.

The precise sizing of the stent graft in thoracic endovascular aortic repair (TEVAR) affects aortic remodeling and hence, further outcome. Covering the proximal entry tear is essential for successful treatment of Type B aortic dissection. Intravascular ultrasound (IVUS) enables real-time aortic diameter assessment, and is especially useful when computed tomography (CT) image quality is poor. IVUS, however, is not routinely utilized due to cost inefficiency. We investigated the impact of IVUS-assisted stent graft sizing on aortic remodeling in TEVAR. In this single-center retrospective study we evaluated patients with Type B aortic dissection undergoing both CT and IVUS before TEVAR. We assessed the aortic diameter at the level of the left subclavian artery via both methods before stent implantation and analyzed due to which method the implanted stent graft was chosen, retrospectively. To determine the degrees of aortic remodeling involved, we evaluated true lumen and false lumen diameters, and total aortic remodeling in CT. We analyzed 45 patients with Type B aortic dissection undergoing TEVAR. The mean ages were 66.9±10.0 years fo0072 IVUS (n = 20) and 62.3±14.2 years for CT-assisted TEVAR (n = 25; p = 0.226). The follow-up time for both groups did not differ between the two groups (IVUS: 22.9±23.1 months, CT: 25.6±23.0 months; p = 0.700). While both methods were associated with advantages regarding aortic remodeling, IVUS-assisted sizing yielded a greater increase in true lumen (30.4±6.2 vs. 25.6±5.3; p = 0.008) and reductions in false lumen (14.4±8.5 vs. 23.9±9.3; p = 0.001) and total aortic diameter (35.5±6.0 vs. 39.9±8.1; p = 0.045). IVUS-guided stent graft sizing in Type B aortic dissection shows beneficial effects on aortic remodeling and might be of additional advantage in aortic diseases, especially when CT image quality is poor.

Comparison of the safety and efficacy of two types of drug-eluting balloons (RESTORE DEB and SeQuent® Please) in the treatment of coronary in-stent restenosis: study protocol for a randomized controlled trial (RESTORE ISR China).

In-stent restenosis (ISR), characterized by neointimal proliferation and/or neoatherosclerosis in the vessel of the stent, can cause a reduction in lumen diameter after stent implantation, which can directly induce the recurrence of angina symptoms or an acute coronary syndrome in patients and is usually life-threatening.[1]–[3] ISR has also been considered as formidable clinical problem for the interventional cardiologists. In recent years, many remarkable improvements in medical technology of percutaneous coronary intervention (PCI), such as first-generation bare metal stents (BMS) and newer-generation drug-eluting stents (DES) have been achieved, which significantly reduce ISR occurrence in patients with PCI.[4],[5] For example, growing evidence has suggested that the safety and efficacy of revascularization procedures of newer-generation DES was greatly superior to those of first generation DES and BMS.[6]–[10] However, ISR rate remains as high as 5% to 10% for patients treated with newer-generation DES at two years.[11] More recently, a newly developed drug-eluting balloon (DEB) coated with paclitaxel, an antiproliferative drug that could inhibit neointimal hyperplasia, had emerged as an alternative therapeutic tool for ISR disease.[12],[13] DEB plays the anti-restenosis efficacy through a high-concentration, rapid local delivery of paclitaxel without the use of polymers on a stent. To date, there are numerous randomized trials performed to compare the safety and efficacy among plain old balloon angioplasty (POBA), DES and DEB for the treatment of ISR.[14] One recent meta-analysis enrolled eight randomized controlled trials and indicated that DEB was a better option for treatment of ISR when compared to POBA.[15] Another meta-analysis showed that DEB and DES have similar efficacy and safety for the treatment of ISR.[16] SeQuent® Please DEB is the only approved product utilized for ISR treatment in China.[17] Currently, a novel paclitaxel-coated balloon (RESTORE DEB) has been invented for the treatment of ISR. However, clinical information on the two different types of DEB in treatment of ISR is limited. This trial aims to compare the safety and efficacy of the RESTOREDEB versus SeQuent® Please DEB for the treatment of coronary ISR in Chinese patients.

Vascular response and healing profile of everolimus-eluting bioresorbable vascular scaffolds for percutaneous treatment of chronic total coronary occlusions: A one-year optical coherence tomography analysis from the GHOST-CTO registry

BackgroundBioresorbable vascular scaffolds (BVS) have been heralded with potential benefits that are especially desired in long lesions, including chronic total occlusions (CTOs). Procedural feasibility and mid-term outcomes of BVS in CTOs have been reported. However, there is still a paucity of data regarding the vascular and healing response to BVS in CTOs evaluated by optical coherence tomography (OCT). MethodsThis study included prospectively 21 patients who had a CTO lesion treated with a BVS. Angiography and OCT scan were recorded at either post-implantation and 1-year follow-up. Quantitative coronary angiography and OCT analyses were performed by an independent core laboratory. ResultsThe angiographic analysis showed a significant increase in the percentage of in-segment diameter stenosis at 1year (11.89±9.5% vs. 21.84±11.7%; p=0.002). The OCT analysis showed a trend (p=0.07) towards increased mean scaffold area and significant reductions in mean lumen diameter (3.1±0.36mm vs. 2.85±0.47mm; p=0.0046), mean lumen area (7.8±1.73mm2 vs. 6.76±2mm2; p=0.0082) and minimal lumen area (5.26±1.86mm2 vs. 3.56±1.52mm2; p<0.0001). Malapposition area and volume decreased from 0.26±0.17mm2 to 0.08±0.1mm2 (p=0.0003) and from 14.17±12.92mm3 to 3.99±4.46mm3 (p=0.0014), respectively. The rate of uncovered or malapposed struts, measured at the frame level, was 5.29±6.48% at 1year. ConclusionsIn a small series of CTO patients treated with BVS implantation, OCT outcomes at 1year displayed an overall favorable vascular response and healing profile.

Randomized comparison of femoropopliteal artery drug-eluting balloons and drug-eluting stents (FOREST trial): Study protocol for a randomized controlled trial

The optimal endovascular treatment for femoropopliteal arterial occlusive disease has yet to be assessed. Patency rates after uncoated balloon angioplasty are disappointing. Although stents have better outcomes, they also have limitations. Intra-arterial stenting may lead to stent thrombosis and flow pattern disruption, which may result in stent fracture or in-stent restenosis. In the past decade, drug-eluting balloons (DEBs) and drug-eluting stents (DESs) have been introduced, and both have been proven to possess antirestenotic features compared with conventional techniques. The objective of this study is to perform a noninferiority analysis of DEBs with provisional bare-metal stenting and primary stenting with DESs in the treatment of femoropopliteal arterial occlusive disease. If DEB with provisional bare-metal stenting proves to be noninferior to primary stenting with DESs, DEBs may be the favorable technique because the postoperative long-term limitations of stents will be restricted. This is a prospective, randomized, controlled, single-blind, multicenter trial. The study population consists of volunteers aged ≥18 years, with chronic, symptomatic peripheral arterial occlusive disease (Rutherford-Baker classification 2 to 5) caused by de novo stenotic or occlusive atherosclerotic lesions of the superficial femoral artery or of the popliteal artery (only segment P1). Subjects will be treated with a DEB and provisional bare-metal stenting (if a stenosis >30% or a flow-limiting dissection persists after prolonged inflation with an uncoated balloon) or with primary stenting with a DES. The study will include 254 patients (ratio 1:1). The primary end point is 2-year freedom from binary restenosis, defined as a lumen diameter reduction of <50% assessed by duplex ultrasound imaging (peak systolic velocity ratio <2.5). Secondary end points are technical success, target lesion revascularization, target vessel revascularization, improvement in ankle-brachial index, improvement in Rutherford classification, amputation rate, and mortality rate.

How to define the hemodynamic significance of an equivocal iliofemoral artery stenosis: Review of literature and outcomes of an international questionnaire.

Purpose The goal of the study was to review current literature regarding the diagnosis of equivocal (50-70%) iliofemoral artery stenosis and compare these findings with the daily practice of an international panel of endovascular experts. Methods The Medline Database was searched for relevant publications, and an electronic survey was sent to experts in the field covering the following topics: definition of an equivocal iliofemoral artery stenosis, angiographic visualization and investigation protocols of an equivocal stenosis, intra-arterial pressure measurements, and definition of hemodynamic significance of an equivocal iliofemoral artery stenosis using a physiologic measure. Results Of the 37 invited endovascular experts, 21 (53.8%) agreed to participate in the survey. Analysis of existing literature shows that the level of evidence for diagnosing equivocal iliofemoral artery stenosis is mediocre and is not being implemented by experts in the field. Conclusion Studies have shown that a stenosis of between 50% and 70% iliofemoral lumen diameter reduction shows a wide range of trans-stenotic pressure gradients. Equivocal iliofemoral artery stenosis can best be identified using three-dimensional quantitative vascular analysis software. Although evidence for a clear hemodynamic cutoff point is weak, performing trans-lesion intra-arterial pressure measurements at rest and during maximal hyperemia is preferred. Diagnosing iliofemoral artery stenosis solely on lumen diameter reduction is inadequate.

Characteristics and Long-Term Prognosis of Patients ≤35 Years of Age with ST Segment Elevation Myocardial Infarction and “Normal or Near Normal” Coronary Arteries

There are scarce data regarding risk factors and prognosis of patients with premature ST segment elevation myocardial infarction (STEMI) and "normal or near normal" coronary arteries (N/NNCAs). We compared the characteristics and long-term prognosis of patients with premature STEMI and N/NNCAs with their counterparts with significant coronary artery disease (CAD). We recruited 330 patients who had STEMI ≤35 years of age and 167 age- and gender-matched controls. All patients underwent coronary angiography. Coronary arteries with no lesions or lesions causing <30% reduction in lumen diameter were defined as N/NNCAs, whereas narrowings causing ≥50% diameter reduction formed the significant CAD group. Lipid profile, homocysteine levels, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism were determined. Sixty patients (18%) had N/NNCAs. Patients with N/NNCAs had lower low-density lipoprotein-cholesterol and higher high-density lipoprotein-cholesterol levels, higher homocysteine levels, and higher prevalence of MTHFR TT genotype (34.6 vs 18%, p = 0.008) compared with patients with significant CAD. After a median follow-up of 8 years, cardiovascular events occurred in 105 (36%) of 291 patients with available follow-up data. Significant CAD was associated with higher risk for recurrent cardiovascular events after adjustment for traditional risk factors (hazard ratio 2.095, 95% confidence interval 1.088 to 3.664, p = 0.022) and additional adjustment for the left ventricular ejection fraction, reperfusion therapy, and persistent smoking (hazard ratio 1.869, 95% confidence interval 1.007 to 3.468, p = 0.041). In conclusion, patients with premature STEMI and N/NNCAs have fewer lipid abnormalities, higher homocysteine levels and prevalence of MTHFR TT genotype, and better long-term prognosis compared with their counterparts with significant CAD.

Minimum wood density of conifers portrays changes in early season precipitation at dry and cold Eurasian regions

Minimum wood density exhibits strong responses to precipitation and, thus, it is a robust proxy of early season water availability. Tracheids fulfil most wood functions in conifers (mechanical support and water transport) and earlywood tracheids account for most hydraulic conductivity within the annual tree ring. Dry conditions during the early growing season, when earlywood is formed, could lead to the formation of narrow tracheid lumens and a dense earlywood. Here, we assessed if there is a negative association between minimum wood density and early growing-season (spring) precipitation. Using dendrochronology, we studied growth and density data at nine forest stands of three Pinaceae species (Larix sibirica, Pinus nigra, and Pinus sylvestris) widely distributed in three cool–dry Eurasian regions from the forest-steppe (Russia, Mongolia) and Mediterranean (Spain) biomes. We measured for each annual tree ring and the common 1950–2002 period the following variables: earlywood and latewood width, and minimum and maximum wood density. As expected, dry early growing season (spring) conditions were associated with low earlywood production but, most importantly, to high minimum density in the three conifer species. The associations between minimum density and spring precipitation were stronger (r = −0.65) than those observed with earlywood width (r = 0.57). We interpret the relationship between spring water availability and high minimum density as a drought-induced reduction in lumen diameter, hydraulic conductivity, and growth. Consequently, forecasted growing-season drier conditions would translate into increased minimum wood density and reflect a reduction in hydraulic conductivity, radial growth, and wood formation. Given the case-study-like nature of this work, more research on other cold–dry sites with additional conifer species is needed to test if minimum wood density is a robust proxy of early season water availability.

Age-related morphological, histological and functional changes in teeth.

Throughout lifetime, the teeth are continuously exposed to numerous chemical and physical impacts, which cause the wear of the dental hard tissues, gingival recession and other oral changes with sometimes subsequent problems. Age-related wear of tooth surfaces reduces the dental enamel thickness and exposes deeper layers of enamel, which have different physical and chemical properties than the surface enamel. Gingival recession is the main causal factor of root caries and dentine hypersensitivity. Age-related changes in dentine include the formation of secondary dentine and the reduction in tubular lumen diameter (dentine sclerosis), which lead to a reduction in the volume of the pulp chamber. In addition to the reduction in the volume of pulp chamber, changes to the dental pulp also include dental pulp calcifications. The age-related physiological changes to the teeth should be carefully distinguished from pathological changes, especially when they induce pain or a negative impact on the oral health-related quality of life (OHRQoL) of the older individuals. Therefore, regular oral examinations coupled with early preventive measures should aim at maintaining oral health until old age.

Interventional Therapy for Transplant Renal Artery Stenosis Is Safe and Effective in Preserving Allograft Function and Improving Hypertension.

To evaluate the outcomes of percutaneous intervention (PI) for transplant renal artery stenosis (TRAS). Doppler ultrasonography was used as the screening tool, and angiography was the diagnostic method for TRAS. The indications for PI were (1) a reduction in lumen diameter of >50% or (2) a mean pressure gradient of >15 mm Hg. Technical success was assessed immediately after the procedure. The short-term results of stenosis were evaluated by serum creatinine (Scr) levels and blood pressure (BP). The long-term results were assessed by graft survival and renal function. From October 2009 to July 2015, a total of 660 patients had kidney transplantation and 22 cases underwent PI. The technical success was 100%. The mean Scr level preintervention was 321.6 ± 167.2 (range, 171.3-862.0) μmol/L, and it decreased to 145.3 ± 44.7 (range, 74.3-260.8) μmol/L 1 month postintervention ( P < .001). Blood pressure was also improved at 1 month postintervention, as assessed by systolic (157.0 ± 13.0 vs 131.0 ± 11.0 mm Hg, P < .001), diastolic (95.0 ± 5.0 vs 77.0 ± 9.0 mm Hg, P < .001), and mean arterial pressure (116.0 ± 7.0 vs 95.0 ± 9.0 mm Hg, P < .001). The patency rate was 100%, 91.7%, and 85.7% at 1, 3, and 12 months, respectively. The secondary patency rate was 100%. Graft survival was 100% during follow-up. There was no significant deterioration in graft function or BP ( P > .05) postintervention when compared to posttransplantation. Percutaneous intervention for TRAS is safe and results in significant improvement both in allograft function and in BP.

CORONARY ARTERY CALCIFICATION

Background: Due to increased risk of CAD and cardiovascular events,prediction of severity and/ or complexity of coronary artery disease (CAD) are valuable.Previously association between severity of CAD and total coronary artery calcium (CAC) scorewas not demonstrated but now there are lot of studies which have proven this associationbut still association between total CAC score and complexity of CAD is not well established.Objective: This study was conducted: (1) To investigate the association between coronaryartery calcium (CAC) score and CAD assessed by CCTA. (2) To find which one of the two, CADseverity or complexity, is better associated with total CAC score in symptomatic patients havingsignificant CAD. Study Design: Observational cross sectional study. Place and Duration: Thestudy was conducted at Shifa International Hospital Faisalabad from March 2013 to June 2016.Materials and Methods: Total 195 consecutive patients of both gender age ≥20 years whowas referred for CT angiography to our hospital and who fulfill the inclusion and exclusioncriteria was included in the study. Before enrollment in the study all patients gave informedconsent. Before CT angiography total CAC score was obtained by non- enhanced CT scans.Demographic characteristics of all patients were obtained. Regarding risk factors for CAD,history of hypertension, diabetes mellitus, family H/O ischemic heart disease and hyperlipidemiawas noted. In all patients before CT angiography, Lab. investigations including complete bloodcount, fasting blood sugar, fasting lipid profile, blood urea and serum creatinine levels wereobtained. Calcium scores were quantified by the scoring algorithm proposed by Agatston et al.All lesions were added to calculate the total CAC score by the Agatston method. Calcium scoreswere divided into the following categories: 0, 1–100, 101–400, and ≥400. The degree of stenosiswas classified into four categories: (1) no stenosis, (2) minimal or mild stenosis (≤50%), (3)moderate stenosis (50%–70%), and (4) severe stenosis (&gt;70%). CAD was defined when lumendiameter reduction was greater than 50% (moderate or severe stenosis). Results: Total 195patients were studied. 136 (69.7%) were male and 59 (30.3%) were female. Mean age of studypopulation was 52.8±10.38 years. 81(41.54%) patients had H/O chest pain, 11(5.64%) hadH/O shortness of breath and 96(49.23%) presented with chest tightness. 104(53.33%) patientswere hypertensive, 71(36.41%) were diabetic, 67(34.35%) had increased cholesterol level. In57 (29.2%) there was no coronary artery disease, 58(29.7%) had mild CAD, 32 (16.4%) hadmoderate and 48 (24.6%) had severe coronary artery disease on CT angiography. Single vesselwas involved in 38(19.5%) patients, 20(10.3%) had two vessel disease and triple vessel diseasewas present in 22(11.3%) patients. 104(53.3%) patients had zero calcium score. 44(22.6%)had CAC score between 1-100, 37 (19%) had CAC score between 101-400 and more than 400CAC score was documented in 10 (5.1%) patients. Conclusions: This study in addition topatient based analysis also confirms the significant relationship between vessels based CADand CAC score. The prevalence of multivessel CAD increased in patients with CACS &gt;100 andthere is 100% incidence of CAD in patients with CACS &gt;1000. Zero calcium cannot exclude thepresence of significant CAD. Our data supports that in symptomatic patients calcium scoring isan additional filter before coronary angiography.

English

Background: Due to increased risk of CAD and cardiovascular events,prediction of severity and/ or complexity of coronary artery disease (CAD) are valuable.Previously association between severity of CAD and total coronary artery calcium (CAC) scorewas not demonstrated but now there are lot of studies which have proven this associationbut still association between total CAC score and complexity of CAD is not well established.Objective: This study was conducted: (1) To investigate the association between coronaryartery calcium (CAC) score and CAD assessed by CCTA. (2) To find which one of the two, CADseverity or complexity, is better associated with total CAC score in symptomatic patients havingsignificant CAD. Study Design: Observational cross sectional study. Place and Duration: Thestudy was conducted at Shifa International Hospital Faisalabad from March 2013 to June 2016.Materials and Methods: Total 195 consecutive patients of both gender age ≥20 years whowas referred for CT angiography to our hospital and who fulfill the inclusion and exclusioncriteria was included in the study. Before enrollment in the study all patients gave informedconsent. Before CT angiography total CAC score was obtained by non- enhanced CT scans.Demographic characteristics of all patients were obtained. Regarding risk factors for CAD,history of hypertension, diabetes mellitus, family H/O ischemic heart disease and hyperlipidemiawas noted. In all patients before CT angiography, Lab. investigations including complete bloodcount, fasting blood sugar, fasting lipid profile, blood urea and serum creatinine levels wereobtained. Calcium scores were quantified by the scoring algorithm proposed by Agatston et al.All lesions were added to calculate the total CAC score by the Agatston method. Calcium scoreswere divided into the following categories: 0, 1–100, 101–400, and ≥400. The degree of stenosiswas classified into four categories: (1) no stenosis, (2) minimal or mild stenosis (≤50%), (3)moderate stenosis (50%–70%), and (4) severe stenosis (&gt;70%). CAD was defined when lumendiameter reduction was greater than 50% (moderate or severe stenosis). Results: Total 195patients were studied. 136 (69.7%) were male and 59 (30.3%) were female. Mean age of studypopulation was 52.8±10.38 years. 81(41.54%) patients had H/O chest pain, 11(5.64%) hadH/O shortness of breath and 96(49.23%) presented with chest tightness. 104(53.33%) patientswere hypertensive, 71(36.41%) were diabetic, 67(34.35%) had increased cholesterol level. In57 (29.2%) there was no coronary artery disease, 58(29.7%) had mild CAD, 32 (16.4%) hadmoderate and 48 (24.6%) had severe coronary artery disease on CT angiography. Single vesselwas involved in 38(19.5%) patients, 20(10.3%) had two vessel disease and triple vessel diseasewas present in 22(11.3%) patients. 104(53.3%) patients had zero calcium score. 44(22.6%)had CAC score between 1-100, 37 (19%) had CAC score between 101-400 and more than 400CAC score was documented in 10 (5.1%) patients. Conclusions: This study in addition topatient based analysis also confirms the significant relationship between vessels based CADand CAC score. The prevalence of multivessel CAD increased in patients with CACS &gt;100 andthere is 100% incidence of CAD in patients with CACS &gt;1000. Zero calcium cannot exclude thepresence of significant CAD. Our data supports that in symptomatic patients calcium scoring isan additional filter before coronary angiography.

Large artery biomechanical, geometrical, and structural remodeling elicited by long-term propranolol administration in an animal model.

Limited attention has been paid to the role of beta-adrenergic blocking agents on large artery function/structure, despite being clinically useful for treating many forms of cardiovascular disease. To assess long-term consequences of beta-blocker administration on the biomechanical properties, geometry, and histological structure of two major elastic arteries. Healthy male rats received water with their food, while beta-blockade was produced in rats by adding propranolol in their drinking water. The thoracic aorta and carotid artery were resected after three months for biomechanical (failure and inflation-extension) testing along with geometrical and histological evaluation. The thoracic aorta presented increased strength longitudinally in propranolol-treated than untreated rats, resulting from increased adventitial collagen content. The distensibility of carotid artery increased in propranolol-treated rats at low-to-physiologic pressures, resulting from decreased medial collagen content. Structural remodeling was characterized by reduced lumen diameter, wall mass, and thickness-to-radius ratio. The latter, together with the greater resorption of the media than adventitia, related with the measured opening angle decrease in propranolol-treated rats. The geometrical/biomechanical remodeling was mediated by the hemodynamic effects of propranolol treatment, namely the reduced blood flow, and served to normalize in vivo hoop stresses as well as vessel compliance.

Magnetic Nanoparticle-Mediated Targeting of Cell Therapy Reduces In-Stent Stenosis in Injured Arteries.

Although drug-eluting stents have dramatically reduced the recurrence of restenosis after vascular interventions, the nonselective antiproliferative drugs released from these devices significantly delay reendothelialization and vascular healing, increasing the risk of short- and long-term stent failure. Efficient repopulation of endothelial cells in the vessel wall following injury may limit complications, such as thrombosis, neoatherosclerosis, and restenosis, through reconstitution of a luminal barrier and cellular secretion of paracrine factors. We assessed the potential of magnetically mediated delivery of endothelial cells (ECs) to inhibit in-stent stenosis induced by mechanical injury in a rat carotid artery stent angioplasty model. ECs loaded with biodegradable superparamagnetic nanoparticles (MNPs) were administered at the distal end of the stented artery and localized to the stent using a brief exposure to a uniform magnetic field. After two months, magnetic localization of ECs demonstrated significant protection from stenosis at the distal part of the stent in the cell therapy group compared to both the proximal part of stent in the cell therapy group and the control (stented, nontreated) group: 1.7-fold (p < 0.001) less reduction in lumen diameter as measured by B-mode and color Doppler ultrasound, 2.3-fold (p < 0.001) less reduction in the ratios of peak systolic velocities as measured by pulsed wave Doppler ultrasound, and 2.1-fold (p < 0.001) attenuation of stenosis as determined through end point morphometric analysis. The study thus demonstrates that magnetically assisted delivery of ECs is a promising strategy for prevention of vessel lumen narrowing after stent angioplasty procedure.

Current and future trends in the lipid lowering therapy.

Atherosclerosis is an inflammatory disease that affects arterial wall. It leads to wall thickening and its instability. As a result a reduction in lumen diameter and blood flow is observed. This manifests predominantly as the affectation of vascular bed of coronary (myocardial infarction), cerebral, carotid (ischemic stroke) or peripheral arteries (limb amputation). One of the most important factors that accelerate atherosclerosis is hyperlipidemia. According to current guidelines the main attention should be focused on the treatment of hyperlipidemia (beside the prevention, which includes proper diet, physical activity and risk factors avoidance). Major attention is given to LDL (low-density lipoprotein) cholesterol (LDL-C) level as primary, and triglyceride level as secondary targets of therapy. As a result of recent clinical findings and continuous research in the field of hypolipidemic drugs it seems practical to review recent data and show potential new pathways that may be useful in the treatment of hyperlipidemia. The review is divided into several parts presenting the widely used and well-known hypolipidemic drugs. In the first part a brief review of contemporary drugs affecting LDL cholesterol is shown. The second part contains information regarding currently available drugs reducing triglycerides level. The third part describes several novel and promising groups of drugs that are still on various steps of clinical development. In the last part drugs affecting HDL (high-density lipoprotein) level were presented.

Na+, HCO3--cotransporter NBCn1 increases pHi gradients, filopodia, and migration of smooth muscle cells and promotes arterial remodelling.

Arterial remodelling can cause luminal narrowing and obstruct blood flow. We tested the hypothesis that cellular acid-base transport facilitates proliferation and migration of vascular smooth muscle cells (VSMCs) and enhances remodelling of conduit arteries. [Formula: see text]-cotransport via NBCn1 (Slc4a7) mediates net acid extrusion and controls steady-state intracellular pH (pHi) in VSMCs of mouse carotid arteries and primary aortic explants. Carotid arteries undergo hypertrophic inward remodelling in response to partial or complete ligation in vivo, but the increase in media area and thickness and reduction in lumen diameter are attenuated in arteries from NBCn1 knock-out compared with wild-type mice. With [Formula: see text] present, gradients for pHi (∼0.2 units magnitude) exist along the axis of VSMC migration in primary explants from wild-type but not NBCn1 knock-out mice. Knock-out or pharmacological inhibition of NBCn1 also reduces filopodia and lowers initial rates of VSMC migration after scratch-wound infliction. Interventions to reduce H(+)-buffer mobility (omission of [Formula: see text] or inhibition of carbonic anhydrases) re-establish axial pHi gradients, filopodia, and migration rates in explants from NBCn1 knock-out mice. The omission of [Formula: see text] also lowers global pHi and inhibits proliferation in primary explants. Under physiological conditions (i.e. with [Formula: see text] present), NBCn1-mediated [Formula: see text] uptake raises VSMC pHi and promotes filopodia, VSMC migration, and hypertrophic inward remodelling. We propose that axial pHi gradients enhance VSMC migration whereas global acidification inhibits VSMC proliferation and media hypertrophy after carotid artery ligation. These findings support a key role of acid-base transport, particularly via NBCn1, for development of occlusive artery disease.

Simvastatin prevents vascular complications in the chronic reactive oxygen species murine model of systemic sclerosis

ABSTRACTAims Systemic sclerosis (SSc) is characterized by vasculopathy and organ fibrosis. Although microvascular alterations are very well characterized, structural and functional abnormalities of large vessels are not well defined. Therefore, we evaluated the effect of simvastatin administration on aortic and small renal arteries thickening, and on myofibroblasts differentiation in a murine model of SSc. Methods and results SSc was induced in BALB/c mice by daily subcutaneous injections of hypochlorous acid (HOCl, 100 μl) for 6 weeks. Mice (n = 23) were randomized to receive: HOCl (n = 10); HOCl plus simvastatin (40 mg/kg; n = 8); or vehicle (n = 5). Simvastatin administration started 30 min after HOCl injection, and up to week 6. Aortic and small renal arteries intima–media thickness was evaluated by histological analysis. Immunostaining for α-smooth muscle actin (SMA), vascular endothelial growth factor receptor 2 (VEGFR2), and CD31 in aortic tissues was performed to evaluate myofibroblast differentiation and endothelial markers.In HOCl-treated mice, intima–media thickening with reduced lumen diameter was observed in the aorta and in small renal arteries and simvastatin administration prevented this increase. Aortic and renal myofibroblasts count, as expressed by α-SMA + density, was lower in the group of mice treated with simvastatin compared to HOCl-treated mice. Simvastatin prevented the reduction in VEGFR2 and CD31 expression induced by HOCl. Conclusions The administration of simvastatin regulates collagen deposition in the aortic tissues and in the small renal arteries by modulating myofibroblasts differentiation and vascular markers. Further studies are needed to better address the effect of statins in the macrovascular component of SSc.

Long-term follow-up of renal arteries after radio-frequency catheter-based denervation using optical coherence tomography and angiography

Optical coherence tomography (OCT) imaging at the time of renal denervation (RDN) showed that procedure might cause spasm, intimal injury or thrombus formation. In the present study, we assessed the healing of renal arteries after RDN using OCT and renal angiography in long-term follow-up. OCT and renal angiography were performed in 12 patients (22 arteries) 18.41±5.83months after RNS. There were no adverse events or complications during the long-term follow-up. In ten patients (83%), significant reductions of blood pressure was achieved without a change of the antihypertensive medications. We demonstrated the presence of 26 areas of focal intimal thickening identified by OCT in 10 (83%) patients and in 14 (63%) arteries. The mean area of focal intimal thickening was 0.054±0.033mm(2). No vessel dissection, thrombus, intimal tear or acute vasospasm were observed during the OCT analysis. Also, the quantitative angiography analysis revealed a significant reduction of the minimal and proximal lumen diameters at follow-up as compared to measurements obtained before RDN. Renal arteries have a favorable "long-term" vessel healing response after RDN. Focal intimal thickening and a modest reduction of the minimal lumen diameter may be observed after RF denervation. Further studies are needed to determine whether intravascular imaging may be helpful in evaluating the vessel healing of RF RDN.