A phenotypical study of vascular smooth muscle cells in human arterial and venous stenosis

Abstract Introduction The primary function of the contractile vascular smooth muscle cells (cVSMCs) is the regulation of the vascular contractility which means the adaptation of the vascular tonus in response to the modulation of the blood pressure and blood flow. The cVSMCs are essentially quiescent, and therefore their synthesis rate is very limited. They are characterized by the expression of contractile proteins specific to the muscular tissue including myosin, h-­‐caldesmon and <-­‐smooth muscle actin (〈-­‐SMA). These contractile cells are strongly represented in the media layer of the arterial wall and, in a smaller proportion, of the vein wall. Their typical stretched-­‐out morphology allows recognizing them by a histological analysis. They do not produce any extracellular matrix (ECM), and do not migrate through the different layers of the vessel wall, and are not directly involved in the development of intimal hyperplasia (IH). Neointimal formation occurs after endothelial disruption leading to complex molecular and biological mechanisms. The de-­‐differentiation of cVSMCs into synthetic VSMCs (sVSMCs) is mentioned as a key element. These non mature cells are able to proliferate and produce ECM. The characterization of the vascular smooth muscle cells (VSMCs) from healthy and stenosed vascular tissues will contribue to the understanding of the different biological processes leading to IH and will be useful for the development of new therapies to interfere with the cVSMCs growth and migration. The aim of our research was to quantify the proportion of cVSMCs and sVSMCs into the healthy and pathologic human blood vessel wall and to characterize their phenotype. Methods We selected 23 specimens of arterial and venous segments from 18 patients. All these specimens were stored in the biobank from the thoracic and vascular surgery departement. 4 groups were designed (group 1 :arteries without lesions (n=3) ;group 2 : veins without lesions (n=1); group 3: arteries with stenosis (n=9); group 4: veins with stenosis (n=10)). Histology: 5µm-­‐sections were made from each sample embedded in paraffin wax and further stained with hematoxylin & eosin (HE), Van Gieson's stain (VGEL) and Masson's Trichrome (TMB). Pathologic tissues were defined using the label that was given to the macroscopic samples by the surgeon and also, based on the histological analysis with HE and VGEL evaluating the presence of a thickened intima. The same was done to the control samples evaluating the absence of thickening. Immunohistochemistry : The primary antibodies were used :〈-­‐SMA, vimentin, h-­‐ caldesmon, calponin, smooth muscle-myosin heavy chain (SM-­‐MHC), tropomyosin-­‐4, retinol binding protein-­‐1 (RBP-­‐1), nonmuscle-­‐myosin heavy chain-­‐B (NM-­‐MHC-­‐B), Von Willebrand factor (VWF). A semi-­‐quantitative assessment of the intensity of each sample stained was performed. Western Blot : Segments of arteries and veins were analyzed using the following primary antibodies :〈-­‐SMA, Calponin, SM-­‐MHC, NM-­‐MHC-­‐B. The given results were then normalized with tubulin. Results Our data showed that, when using immunohistochemistry analysis we found that〈-­‐SMA was mostly expressed in control arteries, whereas NM-­‐MHC-­‐B in the pathologic ones. Using SM-­‐MHC, calponin, vimentin and caldesmon we found no significative differences in the expression of these proteins in the control and in the pathologic samples. Western Blot analysis showed an inverse correlation between healthy and pathological samples as <-­‐ SMA was more expressed in the pathological samples, while NM-­‐MHC-­‐B in the control group; SM-­‐MHC and calponin were mostly expressed in the pathologic samples. Conclusion Our study showed no clear differences between stenotic and control arterial and venous segments using semi-­‐quantitative assessement by immunohistochemistry. Western Blot showed a significant increased expression of 〈-­‐SMA, calponin and SM-­‐MHC in the arteries with stenosis, while NM-­‐MHC-­‐B was mostly expressed in the arteries without lesions. Further studies are needed to track the lineage of VSMCs to understand the mechanisms leading toIH.

Congenital aneurysm of sinus of valsalva ruptured into right ventricle diagnosed by magnetic resonance imaging.

Rupture of a congenital aneurysm of the sinus of Valsalva is a rare congenital cardiac malformation. This case report describes a congenital aneurysm of the sinus of Valsalva which ruptured into the right ventricle in a 3-year-old girl. The exact route of the fistula through the cardiac walls and the localization of the rupture into the right ventricle was not completely defined by two-dimensional and color Doppler echocardiography and could be determined only by magnetic resonance imaging (MRI).

Polypharmacy is Associated with an Increased Risk of Bleeding in Elderly Patients with Venous Thromboembolism.

BACKGROUND: Polypharmacy, defined as the concomitant use of multiple medications, is very common in the elderly and may trigger drug-drug interactions and increase the risk of falls in patients receiving vitamin K antagonists. OBJECTIVE: To examine whether polypharmacy increases the risk of bleeding in elderly patients who receive vitamin K antagonists for acute venous thromboembolism (VTE). DESIGN: We used a prospective cohort study. PARTICIPANTS: In a multicenter Swiss cohort, we studied 830 patients aged ≥ 65 years with VTE. MAIN MEASURES: We defined polypharmacy as the prescription of more than four different drugs. We assessed the association between polypharmacy and the time to a first major and clinically relevant non-major bleeding, accounting for the competing risk of death. We adjusted for known bleeding risk factors (age, gender, pulmonary embolism, active cancer, arterial hypertension, cardiac disease, cerebrovascular disease, chronic liver and renal disease, diabetes mellitus, history of major bleeding, recent surgery, anemia, thrombocytopenia) and periods of vitamin K antagonist treatment as a time-varying covariate. KEY RESULTS: Overall, 413 (49.8 %) patients had polypharmacy. The mean follow-up duration was 17.8 months. Patients with polypharmacy had a significantly higher incidence of major (9.0 vs. 4.1 events/100 patient-years; incidence rate ratio [IRR] 2.18, 95 % confidence interval [CI] 1.32-3.68) and clinically relevant non-major bleeding (14.8 vs. 8.0 events/100 patient-years; IRR 1.85, 95 % CI 1.27-2.71) than patients without polypharmacy. After adjustment, polypharmacy was significantly associated with major (sub-hazard ratio [SHR] 1.83, 95 % CI 1.03-3.25) and clinically relevant non-major bleeding (SHR 1.60, 95 % CI 1.06-2.42). CONCLUSIONS: Polypharmacy is associated with an increased risk of both major and clinically relevant non-major bleeding in elderly patients receiving vitamin K antagonists for VTE.

Your result shows a small abdominal aortic aneurysm (AAA)

This leaflet is given to all men who have attended screening through the Northern Ireland Abdominal Aortic Aneurysm (AAA) Screening Programme and been diagnosed with a small AAA.The leaflet provides: �background information on the AAA screening programme; details on what a small AAA is; information on the monitoring process to regularly check the size of the AAA;lifestyle advice that may help those men diagnosed with an AAA. �Men who have been diagnosed with a small AAA will be invited to a monitoring scan once a year, unless their AAA increases in size to a medium AAA, at which point they will be invited to a monitoring scan once every three months.

Your result shows a medium abdominal aortic aneurysm (AAA)

This leaflet is given to all men who have attended screening through the Northern Ireland Abdominal Aortic Aneurysm (AAA) Screening Programme and been diagnosed with a medium AAA.The leaflet provides: background information on the AAA screening programme; details on what a medium AAA is; information on the monitoring process to regularly check the size of the AAA;lifestyle advice that may help those men diagnosed with an AAA. Men who have been diagnosed with a medium AAA will be invited to a monitoring scan once every three months, unless their AAA increases in size to a large AAA, at which point they will be referred to a team of vascular specialists for further assessment and the possible offer of surgery.

Your result shows a large abdominal aortic aneurysm (AAA) that may need surgery

This leaflet is given to all men who have attended screening through the Northern Ireland Abdominal Aortic Aneurysm (AAA) Screening Programme and been diagnosed with a large AAA.The leaflet provides: background information on the AAA screening programme; details on what a large AAA is; information on the process of referral to a team of vascular specialists;details on the operation to treat a large AAA;important information on the symptoms of a ruptured AAA;lifestyle advice that may help those men diagnosed with an AAA. Men who have been diagnosed with a large AAA will be invited to meet a team of vascular specialists for further assessment within two or three weeks of their scan. Following additional medical tests, the patient may be offered surgery to treat the large AAA. Those men assessed as unsuitable for an operation will continue to be monitored within the vascular service.

Abdominal Aortic Aneurysm (AAA) Screening Programme annual report

This inaugural annual report for the Northern Ireland Abdominal Aortic Aneurysm (AAA) Screening Programme (produced jointly by the Public Health Agency and the Belfast Health and Social Care Trust) looks back on a successful first year for the programme. The Public Health Agency (PHA) is responsible for commissioning and quality assuring the programme. The Belfast Health and Social Care Trust is responsible for providing and managing the programme.Following significant planning, AAA screening was introduced on time in June 2012, as required by the Government's 'Priorities for Action' target. There is no doubt that this was due to sustained partnership working across a wide range of health and social care services within Northern Ireland.

Prevention of Venous Thromboembolism: A Key Patient Safety Priority

Prevention of venous thromboembolism (VTE) is an important part of our strategy to improve patient safety.The Northern Ireland HSC Safety Forum established and facilitated a regional collaborative which developed a single VTE Risk Assessment Tool for N.Ireland.

Abdominal aortic aneurysm (AAA) screening: Things you need to know (English and translations)

This information leaflet is for all men invited to take part in the Northern Ireland Abdominal Aortic Aneurysm (AAA) Screening Programme. Men will automatically be invited for screening in their 65th year, while men aged over 65 can request a scan through the central screening office.

Anévrismes de l'artère poplitée: quelle prise en charge en 2013 ? [Popliteal artery aneurysms: management in 2013].

Although rare, popliteal artery aneurysms are the most common peripheral aneurysms and are frequently associated with abdominal aorta aneurysms. They are often bilateral. One third of patients are asymptomatic at diagnosis, with an insidious evolution. Symptomatic patients may present with symptoms of either acute ischemia or chronic ischemia, or rarely compression or rupture. Surgical exclusion of aneurysm followed by venous bypass remains the treatment of choice. Endovascular treatment is an attractive alternative currently reserved for patients at high risk, with good anatomical criteria. Elective treatment before symptoms onset is preferable given the best results in terms of patency and complications. A conservative approach is allowed for small aneurysms without major embolic risk provided careful monitoring by ultrasound.

Routine use of self-expanding venous cannulas for cardiopulmonary bypass: benefits and pitfalls in 100 consecutive cases.

OBJECTIVE: Assess the performance of self-expanding venous cannulas for routine use in open-heart surgery. METHODS: Prospective study in 100 unselected consecutive patients undergoing open-heart surgery with either remote or central smart venous cannulation. RESULTS: The study focuses on the 76 consecutive adult patients (mean age 59.2+/-17.3 years; 60 males, 16 females) undergoing surgical procedures with total cardiopulmonary bypass for either valve procedures (42/76 patients=55.3%), ascending aorta and arch repair (20/76 patients=26.3%), coronary artery revascularization (13/76 patients=17.1%) or other procedures (11/76 patients=14.5%) with 14/76 patients (18.4%) undergoing redo surgery and 6/76 patients (7.9%) undergoing small access surgery. The mean pump flow achieved by gravity drainage alone accounted for 5.0+/-0.6l/min (=114% of target) in the entire study population (n=76) as compared to the calculated, theoretical pump flow of 4.4+/-0.5l/min (p<0.0001). For the femoral cannulation sub-group (n=35) pump flow achieved by gravity drainage alone accounted for 4.9+/-0.6l/min (=114% of target) as compared to the calculated theoretical pump flow of 4.3+/-0.4l/min (p<0.0001). The corresponding numbers for trans-subclavian cannulation (n=7) are 5.2+/-0.5l/min (111%) for the pump flow achieved by gravity drainage as compared to the theoretical target flow of 4.7+/-0.4l/min. For the central cannulation sub-group (n=34) mean flow achieved by gravity drainage with a self-expanding venous cannula accounted for 5.1+/-0.7l/min (=116% of target) as compared to the calculated theoretical flow of 4.4+/-0.6l/min (p<0.0001). CONCLUSION: Full or more than target flow was achieved in 97% of the patients studied undergoing CPB with self-expanding venous cannulas and gravity drainage. Remote venous cannulation with self-expanding cannulas provides similar flows as central cannulation. Augmentation of venous return is no longer necessary.

Acute retroperitoneal bleeding due to inferior mesenteric artery aneurysm: case report

Background: Visceral artery aneurysms (VAA), although uncommon, are increasingly being detected. We describe a case of spontaneous retroperitoneal hemorrhage from a ruptured IMA aneurysm associated with stenosis of the superior mesenteric artery (SMA) and celiac trunk, successfully treated with surgery. Methods: A 65-year-old man presented with abdominal pain and hypovolemic shock. Abdominal CT scan showed an aneurysm of the inferior mesenteric artery with retroperitoneal hematoma. In addition, an obstructive disease of the superior mesenteric artery and celiac axis was observed. Results: Upon emergency laparotomy a ruptured inferior mesenteric artery aneurysm was detected. The aneurysm was excised and the artery reconstructed by end-to-end anastomosis. Conclusions This report discusses the etiology, presentation, diagnosis and case management of inferior mesenteric artery aneurysms

Clinical presentation and time-course of postoperative venous thromboembolism: Results from the RIETE Registry

There is little literature about the clinical presentation and time-course of postoperative venous thromboembolism (VTE) in different surgical procedures. RIETE is an ongoing, prospective registry of consecutive patients with objectively confirmed, symptomatic acute VTE. In this analysis, we analysed the baseline characteristics, thromboprophylaxis and therapeutic patterns, time-course, and three-month outcome of all patients with postoperative VTE. As of January 2006, there were 1,602 patients with postoperative VTE in RIETE: 393 (25%) after major orthopaedic surgery (145 elective hip arthroplasty, 126 knee arthroplasty, 122 hip fracture); 207 (13%) after cancer surgery; 1,002 (63%) after other procedures. The percentage of patients presenting with clinically overt pulmonary embolism (PE) (48%, 48%, and 50% respectively), the average time elapsed from surgery to VTE (22 +/- 16, 24 +/- 16, and 21 +/- 15 days, respectively), and the three-month incidence of fatal PE (1.3%, 1.4%, and 0.8%, respectively), fatal bleeding (0.8%, 1.0%, and 0.2%, respectively), or major bleeding (2.3%, 2.9%, and 2.8%, respectively) were similar in the three groups. However, the percentage of patients who had received thromboprophylaxis (96%, 76% and 52%, respectively), the duration of prophylaxis (17 +/- 9.6, 13 +/- 8.9, and 12 +/- 11 days, respectively) and the mean daily doses of low-molecular-weight heparin (4,252 +/- 1,016, 3,260 +/- 1,141, and 3,769 +/- 1,650 IU, respectively), were significantly lower in those undergoing cancer surgery or other procedures. In conclusion, the clinical presentation, time-course, and three-month outcome of VTE was similar among the different subgroups of patients, but the use of prophylaxis in patients undergoing cancer surgery or other procedures was suboptimal.

Risk of falls and bleeding in elderly patients with acute venous thromboembolism.

OBJECTIVE: Whether or not a high risk of falls increases the risk of bleeding in patients receiving anticoagulants remains a matter of debate. METHODS: We conducted a prospective cohort study involving 991 patients ≥65 years of age who received anticoagulants for acute venous thromboembolism (VTE) at nine Swiss hospitals between September 2009 and September 2012. The study outcomes were as follows: the time to a first major episode of bleeding; and clinically relevant nonmajor bleeding. We determined the associations between the risk of falls and the time to a first episode of bleeding using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. RESULTS: Four hundred fifty-eight of 991 patients (46%) were at high risk of falls. The mean duration of follow-up was 16.7 months. Patients at high risk of falls had a higher incidence of major bleeding (9.6 vs. 6.6 events/100 patient-years; P = 0.05) and a significantly higher incidence of clinically relevant nonmajor bleeding (16.7 vs. 8.3 events/100 patient-years; P < 0.001) than patients at low risk of falls. After adjustment, a high risk of falls was associated with clinically relevant nonmajor bleeding [subhazard ratio (SHR) = 1.74, 95% confidence interval (CI) = 1.23-2.46], but not with major bleeding (SHR = 1.24, 95% CI = 0.83-1.86). CONCLUSION: In elderly patients who receive anticoagulants because of VTE, a high risk of falls is significantly associated with clinically relevant nonmajor bleeding, but not with major bleeding. Whether or not a high risk of falls is a reason against providing anticoagulation beyond 3 months should be based on patient preferences and the risk of VTE recurrence.