Comparative in vivo study on the healing qualities of four different presealed vascular prostheses

PURPOSE: The purpose of this article is to assess the healing qualities of presealed knitted polyester prostheses. METHODS: Thoracic aortic replacement was performed with grafts with four different coating materials-collagen (CP), albumin (AP), and two with gelatin (GP1/GP2)-in four groups of 15 pigs each. Two weeks, 6 weeks, and 6 months after operation, five pigs of each group were killed. Healing quality was assessed by morphometric analysis of the remaining coating, the extent of tissue ingrowth, and the thickness of the inner layer. RESULTS: The sealant was rapidly absorbed in all prostheses except for the AP (remaining coating at 2 weeks: GP1 22.1%, GP2 34.7%, and CP 68.0% vs AP 97.1% [p < 0.05]), remaining coating at 6 weeks: GP1/GP2 0% and CP 2.5% vs AP 76.7% (p < .01). At 6 months, remaining coating was only detectable in AP (21.5%). At 2 weeks the extent of tissue ingrowth ranged from 65.7% in GP1 and 75.3% in CP to 80% in GP2 versus 8.9% in AP (p < 0.05). There was a slow increase of tissue ingrowth until the sixth postoperative week (GP1 74.4%, GP2 85.0%, and CP 91.3% versus AP 19.6% [p < 0.01]). Thickness of the internal layer varied from 0.11 to 0.21 mm at 2 weeks in all grafts studied and from 1.02 mm (AP) and 1.28 mm (GP2) to 1.39 mm (GP1), versus 0.41 mm in the CP (p < 0.01) after 6 months of implantation. CONCLUSIONS: The type of coating significantly influences the healing properties of knitted polyester prostheses. When used for thoracic aortic replacement in pigs, AP coating clearly results in inferior healing compared with GP1/GP2 or CP impregnation, with digestion of the coating material and tissue ingrowth used as parameters. The thinnest internal layer was found in the CP prostheses, reflecting superior healing properties of this coating in the model studied.

High expression of gastrin-releasing peptide receptors in the vascular bed of urinary tract cancers: promising candidates for vascular targeting applications

Tumoral gastrin-releasing peptide (GRP) receptors are potential targets for diagnosis and therapy using radiolabeled or cytotoxic GRP analogs. GRP-receptor overexpression has been detected in endocrine-related cancer cells and, more recently, also in the vascular bed of selected tumors. More information on vascular GRP-receptors in cancer is required to asses their potential for vascular targeting applications. Therefore, frequent human cancers (n = 368) were analyzed using in vitro GRP-receptor autoradiography on tissue sections with the (125)I-[Tyr(4)]-bombesin radioligand and/or the universal radioligand (125)I-[d-Tyr(6), beta-Ala(11), Phe(13), Nle(14)]-bombesin(6-14). GRP-receptor expressing vessels were evaluated in each tumor group for prevalence, quantity (vascular score), and GRP-receptor density. Prevalence of vascular GRP-receptors was variable, ranging from 12% (prostate cancer) to 92% (urinary tract cancer). Different tumor types within a given site had divergent prevalence of vascular GRP-receptors (e.g. lung: small cell cancer: 0%; adenocarcinoma: 59%; squamous carcinoma: 83%). Also the vascular score varied widely, with the highest score in urinary tract cancer (1.69), moderate scores in lung (0.91), colon (0.88), kidney (0.84), and biliary tract (0.69) cancers and low scores in breast (0.39) and prostate (0.14) cancers. Vascular GRP-receptors were expressed in the muscular vessel wall in moderate to high densities. Normal non-neoplastic control tissues from these organs lacked vascular GRP-receptors. In conclusion, tumoral vessels in all evaluated sites express GRP-receptors, suggesting a major biological function of GRP-receptors in neovasculature. Vascular GRP-receptor expression varies between the tumor types indicating tumor-specific mechanisms in their regulation. Urinary tract cancers express vascular GRP-receptors so abundantly, that they are promising candidates for vascular targeting applications.

Chondrocyte mechanotransduction: effects of compression on deformation of intracellular organelles and relevance to cellular biosynthesis

OBJECTIVE: The effects of mechanical deformation of intact cartilage tissue on chondrocyte biosynthesis in situ have been well documented, but the mechanotransduction pathways that regulate such phenomena have not been elucidated completely. The goal of this study was to examine the effects of tissue deformation on the morphology of a range of intracellular organelles which play a major role in cell biosynthesis and metabolism. DESIGN: Using chemical fixation, high pressure freezing, and electron microscopy, we imaged chondrocytes within mechanically compressed cartilage explants at high magnification and quantitatively and qualitatively assessed changes in organelle volume and shape caused by graded levels of loading. RESULTS: Compression of the tissue caused a concomitant reduction in the volume of the extracellular matrix (ECM), chondrocyte, nucleus, rough endoplasmic reticulum, and mitochondria. Interestingly, however, the Golgi apparatus was able to resist loss of intraorganelle water and retain a portion of its volume relative to the remainder of the cell. These combined results suggest that a balance between intracellular mechanical and osmotic gradients govern the changes in shape and volume of the organelles as the tissue is compressed. CONCLUSIONS: Our results lead to the interpretive hypothesis that organelle volume changes appear to be driven mainly by osmotic interactions while shape changes are mediated by structural factors, such as cytoskeletal interactions that may be linked to extracellular matrix deformations. The observed volume and shape changes of the chondrocyte organelles and the differential behavior between organelles during tissue compression provide evidence for an important mechanotransduction pathway linking translational and post-translational events (e.g., elongation and sulfation of glycosaminoglycans (GAGs) in the Golgi) to cell deformation.

Fetal programming of pulmonary vascular dysfunction in mice: role of epigenetic mechanisms.

Insults during the fetal period predispose the offspring to systemic cardiovascular disease, but little is known about the pulmonary circulation and the underlying mechanisms. Maternal undernutrition during pregnancy may represent a model to investigate underlying mechanisms, because it is associated with systemic vascular dysfunction in the offspring in animals and humans. In rats, restrictive diet during pregnancy (RDP) increases oxidative stress in the placenta. Oxygen species are known to induce epigenetic alterations and may cross the placental barrier. We hypothesized that RDP in mice induces pulmonary vascular dysfunction in the offspring that is related to an epigenetic mechanism. To test this hypothesis, we assessed pulmonary vascular function and lung DNA methylation in offspring of RDP and in control mice at the end of a 2-wk exposure to hypoxia. We found that endothelium-dependent pulmonary artery vasodilation in vitro was impaired and hypoxia-induced pulmonary hypertension and right ventricular hypertrophy in vivo were exaggerated in offspring of RDP. This pulmonary vascular dysfunction was associated with altered lung DNA methylation. Administration of the histone deacetylase inhibitors butyrate and trichostatin A to offspring of RDP normalized pulmonary DNA methylation and vascular function. Finally, administration of the nitroxide Tempol to the mother during RDP prevented vascular dysfunction and dysmethylation in the offspring. These findings demonstrate that in mice undernutrition during gestation induces pulmonary vascular dysfunction in the offspring by an epigenetic mechanism. A similar mechanism may be involved in the fetal programming of vascular dysfunction in humans.

In situ micropillar compression reveals superior strength and ductility but an absence of damage in lamellar bone

Ageing societies suffer from an increasing incidence of bone fractures. Bone strength depends on the amount of mineral measured by clinical densitometry, but also on the micromechanical properties of the hierarchical organization of bone. Here, we investigate the mechanical response under monotonic and cyclic compression of both single osteonal lamellae and macroscopic samples containing numerous osteons. Micropillar compression tests in a scanning electron microscope, microindentation and macroscopic compression tests were performed on dry ovine bone to identify the elastic modulus, yield stress, plastic deformation, damage accumulation and failure mechanisms. We found that isolated lamellae exhibit a plastic behaviour, with higher yield stress and ductility but no damage. In agreement with a proposed rheological model, these experiments illustrate a transition from a ductile mechanical behaviour of bone at the microscale to a quasi-brittle response driven by the growth of cracks along interfaces or in the vicinity of pores at the macroscale.

Surgical treatment of upper, middle and lower cervical injuries and non-unions by anterior procedures

The goals of any treatment of cervical spine injuries are: return to maximum functional ability, minimum of residual pain, decrease of any neurological deficit, minimum of residual deformity and prevention of further disability. The advantages of surgical treatment are the ability to reach optimal reduction, immediate stability, direct decompression of the cord and the exiting roots, the need for only minimum external fixation, the possibility for early mobilisation and clearly decreased nursing problems. There are some reasons why those goals can be reached better by anterior surgery. Usually the bony compression of the cord and roots comes from the front therefore anterior decompression is usually the procedure of choice. Also, the anterior stabilisation with a plate is usually simpler than a posterior instrumentation. It needs to be stressed that closed reduction by traction can align the fractured spine and indirectly decompress the neural structures in about 70%. The necessary weight is 2.5 kg per level of injury. In the upper cervical spine, the odontoid fracture type 2 is an indication for anterior surgery by direct screw fixation. Joint C1/C2 dislocations or fractures or certain odontoid fractures can be treated with a fusion of the C1/C2 joint by anterior transarticular screw fixation. In the lower and middle cervical spine, anterior plating combined with iliac crest or fibular strut graft is the procedure of choice, however, a solid graft can also be replaced by filled solid or expandable vertebral cages. The complication of this surgery is low, when properly executed and anterior surgery may only be contra-indicated in case of a significant lesion or locked joints.

Determinants of haemodialysis access survival

Vascular access patency is of vital importance for patients requiring haemodialysis. This analysis validates potential risk factors and benefits in patients undergoing vascular access procedures.

Prognosis of Atrial Fibrillation in Patients with Symptomatic Peripheral Arterial Disease: Data from the REduction of Atherothrombosis for Continued Health (REACH) Registry

BACKGROUND: Atrial fibrillation (AF) is a significant risk factor for cardiovascular (CV) mortality. This study aims to evaluate the prognostic implication of AF in patients with peripheral arterial disease (PAD). METHODS: The International Reduction of Atherothrombosis for Continued Health (REACH) Registry included 23,542 outpatients in Europe with established coronary artery disease, cerebrovascular disease (CVD), PAD and/or >/=3 risk factors. Of these, 3753 patients had symptomatic PAD. CV risk factors were determined at baseline. Study end point was a combination of cardiac death, non-fatal myocardial infarction (MI) and stroke (CV events) during 2 years of follow-up. Cox regression analysis adjusted for age, gender and other risk factors (i.e., congestive heart failure, coronary artery re-vascularisation, coronary artery bypass grafting (CABG), MI, hypertension, stroke, current smoking and diabetes) was used. RESULTS: Of 3753 PAD patients, 392 (10%) were known to have AF. Patients with AF were older and had a higher prevalence of CVD, diabetes and hypertension. Long-term CV mortality occurred in 5.6% of patients with AF and in 1.6% of those without AF (p<0.001). Multivariable analyses showed that AF was an independent predictor of late CV events (hazard ratio (HR): 1.5; 95% confidence interval (CI): 1.09-2.0). CONCLUSION: AF is common in European patients with symptomatic PAD and is independently associated with a worse 2-year CV outcome.

Impact of long-term corticosteroid therapy on the distribution pattern of lower limb atherosclerosis

OBJECTIVE: Ectopic calcification and mediacalcinosis can be promoted by corticosteroid use. Aim of the present investigation is to describe macrovascular disease features in patients with long-term corticosteroid therapy and symptomatic lower limb peripheral arterial occlusive disease (PAD). METHODS: A consecutive series of 2783 patients undergoing clinical and angiographic work-up of PAD were screened for long-term (>5 years) corticosteroid use (group A). Comparison was performed to a randomly selected age-, sex- and risk factor-matched PAD control cohort from the same series without corticosteroid use (group B). Patients with diabetes mellitus or severe renal failure were excluded. Arterial calcification was evaluated by qualitative assessment on radiographic images. Severity of atherosclerotic lesions was analysed from angiographic images using a semi-quantitative score (Bollinger score). RESULTS: In general, 12 patients (5 males, mean age 78.5 +/- 9.0 years) with 15 ischaemic limbs qualified to be enrolled in group A and were compared to 23 matching control patients (6 2 males, mean age 79.5 +/- 6 years) with 32 ischaemic limbs. Incompressibility of ankle arteries determined by measurement of the ankle-brachial index was seen in 12 limbs (80%) in group A compared to 3 limbs (9%) in group B (p = 0.0009). No significant difference was found comparing group A and B for segmental calcification, whereas comparison of the atherosclerotic burden using the angiographic severity score showed a significantly higher score at the infragenicular arterial level in group A (p = 0.001). CONCLUSION: Findings suggest that the long-term corticosteroid therapy is associated with a distally accentuated, calcifying peripheral atherosclerosis inducing arterial incompressibility. This occlusion pattern is comparable to patients with renal failure or diabetes. Further research is required to support our observations.

Renal insufficiency is independently associated with a distal distribution pattern of symptomatic lower-limb atherosclerosis

Objectives The purpose of this study was to assess the impact of renal insufficiency (RI) on the distribution pattern of peripheral arterial disease (PAD). We hypothesised that RI is associated with a distally accentuated involvement of the peripheral arterial tree. Design This is a retrospective analysis. Materials and Methods Analysis was based on a consecutive series of 2709 patients with chronic PAD of atherosclerotic origin undergoing primary endovascular treatment of lower-extremity arteries. Atherosclerotic pattern was grouped into femoropopliteal (n = 2085) and infragenicular (n = 892) disease according to target lesions treated while using iliac disease (n = 1133) as reference. Univariable and multivariable multinomial regression analyses were performed to assess relation with RI. Results are shown as relative risk ratio (RRRs) with 95% confidence intervals (95% CIs). A p < 0.05 was considered statistically significant. RI was defined as glomerular filtration rate (GFR) < 60 ml min−1 1.73 m−2. Results Presence of RI was an independent risk factor for a centrifugal lesion pattern (RRR 1.48, 95% CI: 1.17–1.86, p = 0.001). Moreover, a decrease in GFR by 10 ml min−1 1.73 m−2 was associated with an RRR of 1.08 for below-the-knee arterial disease (95% CI: 1.03–1.13, p = 0.003). Conclusion Presence and severity of RI are independent predictors of a distal obstructive pattern in patients with symptomatic PAD.

Endovascular treatment of popliteal artery aneurysms: a single-center experience

PURPOSE: To evaluate the use of covered stent-grafts in the endovascular treatment (ET) of popliteal artery aneurysms (PAAs). MATERIALS AND METHODS: A retrospective analysis was conducted over a period of 52 months in 18 consecutive patients (17 men; mean age +/- SD, 70 years +/- 11) undergoing ET of PAAs with the Viabahn endograft in a single center. Patient symptoms, aneurysm characteristics, technical outcomes, complications, and follow-up were assessed. RESULTS: Aneurysm diameters ranged from 12 to 51 mm with a mean of 30 mm (+/-11). Thirteen aneurysms (72.2%) were partially thrombosed and 12 patients (66.6%) had symptoms of lower limb ischemia at presentation (11 chronic and one acute). The technical success rate was 94%. Intraprocedural emboli and endoleak occurred in one and two patients, respectively. Fourteen patients were available for follow-up after successful treatment, with a mean follow-up time of 15 months (range, 7-37 months). All stent-grafts were patent after 1 month, with no mortality or limb loss. The primary patency rate with complete exclusion of the aneurysm at 6 months was 86%. Pre- and postprocedural noninvasive arterial studies were available in 10 patients, demonstrating improvement of the ankle-brachial index from 0.96 +/- 0.41 to 1.17 +/- 0.18, respectively (P = .06). CONCLUSIONS: Endovascular stent-graft repair of PAAs is a feasible treatment option. However, further follow-up studies regarding the durability of results are required.

Impact of obesity on venous hemodynamics of the lower limbs

Obesity is a risk factor for chronic venous insufficiency and venous thromboembolism. The aim of this study was to compare venous flow parameters of the lower limbs assessed by duplex ultrasound scanning in obese and nonobese individuals according to body mass index (BMI).

The Next 10 years in the Management of Peripheral Artery Disease: Perspectives from The 'PAD 2009' Conference

OBJECTIVES: To briefly inform on the conclusions from a conference on the next 10 years in the management of peripheral artery disease (PAD). DESIGN OF THE CONFERENCE: International participation, invited presentations and open discussion were based on the following issues: Why is PAD under-recognised? Health economic impact of PAD; funding of PAD research; changes of treatment options? Aspects on clinical trials and regulatory views; and the role of guidelines. RESULTS AND CONCLUSIONS: A relative lack of knowledge about cardiovascular risk and optimal management of PAD patients exists not only among the public, but also in parts of the health-care system. Specialists are required to act for improved information. More specific PAD research is needed for risk management and to apply the best possible evaluation of evidence for treatment strategies. Better strategies for funding are required based on, for example, public/private initiatives. The proportion of endovascular treatments is steadily increasing, more frequently based on observational studies than on randomised controlled trials. The role of guidelines is therefore important to guide the profession in the assessment of most relevant treatment.

Safety and Efficacy of Ranibizumab in Diabetic Macular Edema (RESOLVE Study): A 12-month, randomized, controlled, double-masked, multicenter phase II study

The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center.