Vascular surgical training currently has to cope with various challenges, including restrictions on work hours, significant reduction of open surgical training cases in many countries, an increasing diversity of open and endovascular procedures, and distinct expectations by trainees. Even more important, patients and the public no longer accept a "learning by doing" training philosophy that leaves the learning curve on the patient's side. The Vascular International (VI) Foundation and School aims to overcome these obstacles by training conventional vascular and endovascular techniques before they are applied on patients. To achieve largely realistic training conditions, lifelike pulsatile models with exchangeable synthetic arterial inlays were created to practice carotid endarterectomy and patch plasty, open abdominal aortic aneurysm surgery, and peripheral bypass surgery, as well as for endovascular procedures, including endovascular aneurysm repair, thoracic endovascular aortic repair, peripheral balloon dilatation, and stenting. All models are equipped with a small pressure pump inside to create pulsatile flow conditions with variable peak pressures of ~90 mm Hg. The VI course schedule consists of a series of 2-hour modules teaching different open or endovascular procedures step-by-step in a standardized fashion. Trainees practice in pairs with continuous supervision and intensive advice provided by highly experienced vascular surgical trainers (trainer-to-trainee ratio is 1:4). Several evaluations of these courses show that tutor-assisted training on lifelike models in an educational-centered and motivated environment is associated with a significant increase of general and specific vascular surgical technical competence within a short period of time. Future studies should evaluate whether these benefits positively influence the future learning curve of vascular surgical trainees and clarify to what extent sophisticated models are useful to assess the level of technical skills of vascular surgical residents at national or international board examinations. This article gives an overview of our experiences of >20 years of practical training of beginners and advanced vascular surgeons using lifelike pulsatile vascular surgical training models.

Summary. Background: Atherosclerosis is considered to be a chronic inflammatory disorder. Activation of the complement cascade is a major aspect of chronic inflammatory diseases. Complement components were identified in atherosclerotic plaques, and a correlation between adverse events and C5a plasma levels was found. These findings support the notion that complement activation contributes to development and progression of atherosclerotic lesions. Objectives: We investigated whether complement components C3a and C5a regulate plasminogen activator inhibitor (PAI-1) in human macrophages. Methods: Human monocyte-derived macrophages (MDM) and human plaque macrophages were cultured and incubated with the complement component C5a. Results: C5a increased PAI-1 up to 11-fold in human MDM and up to 2.7-fold in human plaque macrophages. These results were confirmed at the mRNA level using real time-polymerase chain reaction. Pertussis toxin or anti-C5aR/CD88 antibody completely abolished the effect of recombinant human C5a on PAI-1 production, suggesting a role of the C5a receptor. Experiments with antitumor necrosis factor (TNF)-a antibodies and tiron showed that the effect of C5a was not mediated by TNF-a or oxidative burst. Furthermore C5a induced NF-jB binding to the cis element in human macrophages and the C5a-induced increase in PAI-1 was completely abolished by an NF-jB inhibitor. Conclusions: We conclude that C5a upregulates PAI-1 in macrophages via NF-jB activation. We hypothesize that -if operative in vivo -this effect could favor thrombus development and thrombus stabilization in the lesion area. On the other hand one could speculate that C5a-induced upregulation of PAI-1 in plaque macrophages could act as a defense mechanism against plaque destabilization and rupture.

Macrophages as inflammatory cells are involved in the pathogenesis of atherosclerosis that today is recognized as an inflammatory disease. Activation of coagulation leads to the late complication of atherosclerosis, namely atherothrombosis with its clinical manifestations stroke, unstable angina, myocardial infarction, and sudden cardiac death. Thus inflammation and coagulation play fundamental roles in the pathogenesis of atherosclerosis. We show that the coagulation enzyme thrombin up-regulates oncostatin M (OSM), a pleiotropic cytokine implicated in the pathophysiology of vascular disease, in human monocyte-derived macrophages (MDMs) up to 16.8-fold. A similar effect was seen in human peripheral blood monocytes and human plaque macrophages. In MDMs, the effect of thrombin on OSM was abolished by PPACK and mimicked by a PAR-1-specific peptide. Thrombin induced phosphorylation of ERK1/2 and p38 in MDMs. The ERK1/2 inhibitor PD98059 blocked the effect of thrombin on OSM production in MDMs, whereas the p38 inhibitor SB202190 had no effect. Thrombin induced translocation of c-fos and c-jun to the nucleus of MDMs. Using OSM promoter-luciferase reporter constructs transfected into MDMs, we show that a functional AP-1 site is required for promoter activation by thrombin. We present another link between coagulation and inflammation, which could impact on the pathogenesis of atherosclerosis. IntroductionMacrophages as inflammatory cells, which produce an array of inflammatory mediators, growth factors, and proteases are critically involved in the pathogenesis of atherosclerosis that today is recognized as an inflammatory disease. 1,2 Rupture of advanced atherosclerotic lesions leads to activation of the coagulation cascade, resulting in thrombin generation and subsequently in atherothrombosis with its clinical complications such as stroke, unstable angina, myocardial infarction, and sudden cardiac death, which are the most common causes of morbidity and mortality in the Western world today. [3][4][5][6][7][8] The central coagulation enzyme thrombin acts as a proinflammatory mediator and is chemotactic for monocytes and stimulates their proliferation and phagocytic activity. [9][10][11][12][13] In monocytes and macrophages, thrombin induces the production of inflammatory cytokines with well-established roles in cardiovascular disease such as interleukin-1 (IL-1), monocyte chemoattractant protein-1, and IL-6, a member of the IL-6 family of cytokines. [14][15][16][17][18] In this paper we have addressed the question whether thrombin affects the expression of yet another member of the IL-6 family of cytokines, which is produced mainly by macrophages, namely oncostatin-M (OSM) in these cells. This pleiotropic cytokine, which plays a critical role in numerous physiologic and pathophysiologic processes including inflammation, hematopoiesis, tissue remodeling, development, and cell growth, has been implicated recently in the pathophysiology of cardiovascular disease. [19][20][21][22][23][24] In vascular smooth muscle cells, O...

Although replanting the IMA did not confer a statistically significant reduction of perioperative morbidity or mortality in this study, it appears that older patients and patients with increased intraoperative blood loss might benefit from IMA replantation, because this maneuver does not increase perioperative morbidity or substantially increase operation time.

Objective-Macrophages produce the cytokine oncostatin M (OSM), which beside other functions is also involved in inflammation. The complement component C5a mobilizes and activates these cells at inflammatory sites. We examined the effect of C5a on OSM production in human monocytes and in human monocyte-derived macrophages. Methods and Results-For macrophage transformation peripheral blood monocytes were cultivated for 8 to 10 days in the presence of human serum. C5a significantly increased in these cells OSM antigen as determined by specific ELISA and mRNA as quantitated by real-time polymerase chain reaction in these cells as well as in plaque macrophages. This effect was blocked by antibodies against the receptor C5aR/CD88 and by pertussis toxin. The C5a-induced phosphorylation of p38 and JNK and the C5a-induced increase in OSM production in macrophages was abolished by 2 p38 inhibitors and by a JNK inhibitor. Furthermore C5a increased the nuclear translocation of c-fos and c-jun. Using different OSM promoter deletion mutant constructs we show that the putative AP-1 element is responsible for activation of OSM promoter activity by C5a. Key Words: atherosclerosis Ⅲ macrophages Ⅲ inflammation Ⅲ complement Ⅲ oncostatin M M acrophages by producing a vast array of biomolecules play a key role in a variety of physiological and pathophysiological processes such as immunity, inflammation, and tissue remodeling. 1 Among these biomolecules are various inflammatory cytokines such as tumor necrosis factor (TNF)-␣, interleukin (IL)-1, or IL-6. 2 Macrophages are also considered to be the major producers of oncostatin M (OSM), which is a multifunctional cytokine belonging to the glycoprotein 130 (gp130) receptor cytokine family. 3-5 OSM was originally isolated from phorbol 12-myristate 13-acetate (PMA)-treated human histolytic lymphoma U937 cells and plays a critical role in numerous physiological and pathophysiological events including inflammation, hematopoiesis, tissue remodeling, development, and cell growth. 6,7 Besides macrophages also T cells, neutrophils, osteoblasts, dendritic cells, Kaposi's sarcoma cells, and microglia produce OSM. 8 -13 Its expression is upregulated by granulocyte-macrophage colony stimulating factor (GM-CSF), IL-3, human chorionic gonadotropin (hCG), HIV-1, lipopolysaccharide (LPS), cisplatin, or prostaglandin (PG) E2. 11,[13][14][15][16] The potent anaphylatoxin C5a is generated during complement activation through cleavage of C5 and is released at the inflammatory site. There, C5a mediates immune and inflammatory processes such as increased vascular permeability, spasmogenesis, immune regulation, and the release of a variety of inflammatory cytokines and mediators. 17,18 C5a is a strong chemoattractant and is involved in the recruitment of inflammatory cells such as T lymphocytes, eosinophils, neutrophils, and monocytes and is regarded as the most potent chemoattractant for the latter 2 cell types. 19,20 It contributes to rapid mobilization of phagocytic cells to and activation of these cells...

The physical capacity of negative pressure wound therapy (NPWT) dressing on the bacterial growth in an in vitro wound model was investigated. Standardised wounds were contaminated with a clinical Staphylococcus aureus strain and incubated at 35 degrees C for 6 hours. Four wounds were treated with continuous negative pressure (125 mmHg) and four controls without. Bacterial load per gram tissue and per gram polyurethane sponge were measured after 24, 36 and 72 hours. Without negative pressure, the initial mean S. aureus load per gram tissue was 1.42 x 10(4), with negative pressure 1.84 x 10(4), P = 0.294. After 24, 36 and 72 hours, both models yielded comparable numbers of organisms (24 hours: P = 0.081; 48 hours: P = 0.455; 72 hours: P = 0.825, respectively). Bacterial load of sponges with or without negative pressure also did not differ. Over a period of 72 hours, sponges with negative pressure yielded 1.60 x 10(8), those without negative pressure yielded 1.74 x 10(8) CFU/g sponge (P = 0.876). In non vital tissue without the influence of the immune system, the bacterial load did not decrease in our in vitro model using an NPWT dressing. This observation was independent of the physical effect of continuous negative pressure at 125 mmHg. The reduction in bacteria demonstrated in previous studies appears to be caused by other effects than physical suction alone. However, the results obtained are limited as non viable tissue was used and the effect of suction on dead tissue might be very different from that occurring on perfused tissue, for example, in an animal model or in patients.

Both antimicrobial collagen-coated polymer vascular grafts showed bactericidal activity against methicillin-resistant Staphylococcus aureus in vitro. Although the silver-triclosan vascular graft showed a faster antimicrobial efficacy, the silver graft exhibited its antimicrobial properties after 24 hours. Which concept will protect an implanted vascular prosthetic graft better from bacterial contamination and subsequent infection needs to be investigated further in in vivo animal and clinical studies.

Our data confirm proposed potential benefits attributable to the minimally invasive nature of pEVAR while demonstrating cost-effectiveness despite the additional cost of closure devices. Taking into account pEVAR failures still does not increase pEVAR costs over cEVAR. Further considering reduced postoperative pain and wound complications, the technique deserves consideration in suitable patients.