Adrenomedullin Is Associated With Surgical Trauma and Impaired Renal Function in Vascular Surgery Patients.

BACKGROUND:: Patients undergoing vascular surgery are prone to perioperative organ injury because of both higher prevalence of cardiovascular risk factors and the extent of surgery. Early detection of organ failure is essential to facilitate appropriate medical care. Midregional pro-adrenomedullin (MR-proADM) has been investigated in acute medical care settings to guide clinical decision-making regarding patient pathways and to identify patients prone to imminent cardiovascular or inflammatory complications. In this study, we evaluated the impact of perioperative MR-proADM levels as an early marker of perioperative cardiovascular and inflammatory stress reactions and kidney injury. METHODS:: The study was conducted as a monocentric, prospective, noninterventional trial at Hannover Medical School, Germany. A total of 454 consecutive patients who underwent open vascular surgery were followed from the day prior to until 30 days after surgery. The composite primary end point was defined as the occurrence of major adverse cardiac events (MACEs), acute kidney injury (AKI), or systemic inflammatory response syndrome (SIRS). Measurements were correlated with both medical history and postoperative MACE, AKI, or SIRS using univariate and multivariate regression analysis. RESULTS:: One hundred thirty-nine (31%) of the patients reached the primary end point within the study interval. Midregional pro-adrenomedullin change was associated with the combined primary end point and with the intensity of surgical trauma. Midregional pro-adrenomedullin change was increased in patients reaching the secondary end points, SIRS (optimal cutoff: 0.2 nmol/L) and AKI (optimal cutoff: 0.7 nmol/L), but not in patients with MACEs. CONCLUSION:: Increased levels of MR-proADM within the perioperative setting (1) were linked to the invasiveness of surgery and (2) identified patients with ongoing loss of renal function. Increased MR-proADM levels may therefore identify a subgroup of patients prone to excessive cardiovascular stress but did not directly correlate with adverse cardiac events. Consistently low levels of MR-proADM may identify a subgroup of patients with acceptable low risk to guide discharge from high-density care units.

Perioperative levels and changes of high-sensitivity troponin T are associated with cardiovascular events in vascular surgery patients.

OBJECTIVES: Myocardial infarction after major surgery is frequent, drives outcome, and consumes health resources. Specific prediction and detection of perioperative myocardial infarction is an unmet clinical need. With the widespread use of high-sensitive cardiac troponin T assays, positive tests become frequent, but their diagnostic or prognostic impact is arguable. We, therefore, studied the association of routinely determined pre- and postoperative high-sensitive cardiac troponin T with the occurrence of major adverse cardiac events. DESIGN: This study was a prospective non-interventional trial. SETTING: This study was conducted at Hannover Medical School in Germany. PATIENTS: A total of 455 patients undergoing open vascular surgery were followed for 30 days for the occurrence of major adverse cardiac events. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Preoperative and 24-hour postoperative high-sensitive cardiac troponin T measurements and the respective changes were correlated to medical history and the occurrence of major adverse cardiac events (cardiovascular death, myocardial infarction, and ischemia). Pre- and postoperative high-sensitive cardiac troponin T measurements demonstrated a majority of patients with detectable troponin levels preoperatively and an increase over the 24 hours after surgery. The level of high-sensitive cardiac troponin T was significantly associated with preexisting diseases that constitute the Lee's Revised Cardiac Risk Index. A preoperative high-sensitive cardiac troponin T greater than or equal to 17.8 ng/L and a perioperative high-sensitive cardiac troponin T change greater than or equal to 6.3 ng/L are independently associated with the occurrence of major adverse cardiac events. Adding high-sensitive cardiac troponin T absolute change to the Revised Cardiac Risk Index improves the risk predictive accuracy of the score as evidenced by increased area under receiver operating characteristic and significant reclassification effects. CONCLUSIONS: The risk predictive power of high-sensitive cardiac troponin T change in addition to the Revised Cardiac Risk Index could facilitate 1) detection of patients at highest risk for perioperative myocardial ischemia, 2) evaluation and development of cardioprotective therapeutic strategies, and 3) decisions for admission to and discharge from high-density care units.

Fabrication of heart tubes from iPSC derived cardiomyocytes and human fibrinogen by rotating mold technology.

Due to its structural and functional complexity the heart imposes immense physical, physiological and electromechanical challenges on the engineering of a biological replacement. Therefore, to come closer to clinical translation, the development of a simpler biological assist device is requested. Here, we demonstrate the fabrication of tubular cardiac constructs with substantial dimensions of 6 cm in length and 11 mm in diameter by combining human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and human foreskin fibroblast (hFFs) in human fibrin employing a rotating mold technology. By centrifugal forces employed in the process a cell-dense layer was generated enabling a timely functional coupling of iPSC-CMs demonstrated by a transgenic calcium sensor, rhythmic tissue contractions, and responsiveness to electrical pacing. Adjusting the degree of remodeling as a function of hFF-content and inhibition of fibrinolysis resulted in stable tissue integrity for up to 5 weeks. The rotating mold device developed in frame of this work enabled the production of tubes with clinically relevant dimensions of up to 10 cm in length and 22 mm in diameter which-in combination with advanced bioreactor technology for controlled production of functional iPSC-derivatives-paves the way towards the clinical translation of a biological cardiac assist device.

Fabrication and biomechanical characterization of a spider silk reinforced fibrin-based vascular prosthesis.

With fibrin-based vascular prostheses, vascular tissue engineering offers a promising approach for the fabrication of biologically active regenerative vascular grafts. As a potentially autologous biomaterial, fibrin exhibits excellent hemo- and biocompatibility. However, the major problem in the use of fibrin constructs in vascular tissue engineering, which has so far prevented their widespread clinical application, is the insufficient biomechanical stability of unprocessed fibrin matrices. In this proof-of-concept study, we investigated to what extent the addition of a spider silk network into the wall structure of fibrin-based vascular prostheses leads to an increase in biomechanical stability and an improvement in the biomimetic elastic behavior of the grafts. For the fabrication of hybrid prostheses composed of fibrin and spider silk, a statically cast tubular fibrin matrix was surrounded with an envelope layer of Trichonephila edulis silk using a custom built coiling machine. The fibrin matrix was then compacted and pressed into the spider silk network by transluminal balloon compression. This manufacturing process resulted in a hybrid prosthesis with a luminal diameter of 4 mm. Biomechanical characterization revealed a significant increase in biomechanical stability of spider silk reinforced grafts compared to exclusively compacted fibrin segments with a mean burst pressure of 362 ± 74 mmHg vs. 213 ± 14 mmHg (p < 0.05). Dynamic elastic behavior of the spider silk reinforced grafts was similar to native arteries. In addition, the coiling with spider silk allowed a significant increase in suture retention strength and resistance to external compression without compromising the endothelialization capacity of the grafts. Thus, spider silk reinforcement using the abluminal coiling technique represents an efficient and reproducible technique to optimize the biomechanical behavior of small-diameter fibrin-based vascular grafts.

Development, comparative structural analysis, and first in vivo evaluation of acellular implanted highly compacted fibrin tubes for arterial bypass grafting.

The generation of small-caliber vascular grafts remains a significant challenge within the field of tissue engineering. In pursuit of this objective, fibrin has emerged as a promising scaffold material. However, its lack of biomechanical strength has limited its utility in the construction of tissue engineered vascular grafts. We have previously reported about the implementation of centrifugal casting molding to generate compacted fibrin tubes with a highly increased biomechanical strength. In this study, we conducted a structural analysis of compacted fibrin tubes using the open-source software Fiji/BoneJ. The primary aim was to validate the hypothesis that the compaction of fibrin leads to a more complex structure characterized by increased crosslinking of fibrin fibers. Structural analysis revealed a strong correlation between fibrin's structure and its biomechanical strength. Moreover, we enhanced fibrin compaction in a subsequent dehydration process, leading to a significant increase of biomechanical strength. Thus, the presented method in combination with an adequate imaging, e.g., micro-CT, has substantial potential as a powerful tool for quality assurance in the development of fibrin-based vascular grafts. To validate this concept, acellular highly compacted fibrin tubes were implanted as substitutes of a segment of the carotid artery in a sheep model (n = 4). After 6 months explanted segments exhibited distinct remodeling, transitioning into newly formed arteries.

A Hyperdynamic Arteriovenous Fistula Aneurysm After Long Time Renal Transplantation.

CONCLUSION: Closure of arteriovenous fistula should be considered in patients who underwent successful renal transplantation to avoid potential complications that may result from the presence of unused fistula especially, in patients who are predisposed to aneurysm formation in the future.

Mechanical Stimulation Induces Vasa Vasorum Capillary Alignment in a Fibrin-Based Tunica Adventitia.

Generation of bioartificial blood vessels with a physiological three-layered wall architecture is a long pursued goal in vascular tissue engineering. While considerable advances have been made to resemble the physiological tunica intima and media morphology and function in bioartificial vessels, only very few studies have targeted the generation of a tunica adventitia, including its characteristic vascular network known as the vasa vasorum, which are essential for graft nutrition and integration. In healthy native blood vessels, capillary vasa vasorum are aligned longitudinally to the vessel axis. Thus, inducing longitudinal alignment of capillary tubes to generate a physiological tunica adventitia morphology and function may be advantageous in bioengineered vessels as well. In this study, we investigated the effect of two biomechanical stimulation parameters, longitudinal tension and physiological cyclic stretch, on tube alignment in capillary networks formed by self-assembly of human umbilical vein endothelial cells in tunica adventitia-equivalents of fibrin-based bioartificial blood vessels. Moreover, the effect of changes of the biomechanical environment on network remodeling after initial tube formation was analyzed. Both, longitudinal tension and cyclic stretch by pulsatile perfusion induced physiological capillary tube alignment parallel to the longitudinal vessel axis. This effect was even more pronounced when both biomechanical factors were applied simultaneously, which resulted in an alignment of 57.2 ± 5.2% within 5° of the main vessel axis. Opposed to that, a random tube orientation was observed in vessels incubated statically. Scanning electron microscopy showed that longitudinal tension also resulted in longitudinal alignment of fibrin fibrils, which may function as a guidance structure for directed capillary tube formation. Moreover, existing microvascular networks showed distinct remodeling in response to addition or withdrawal of mechanical stimulation with corresponding increase or decrease of the degree of alignment. With longitudinal tension and cyclic stretch, we identified two mechanical stimuli that facilitate the generation of a prevascularized tunica adventitia-equivalent with physiological tube alignment in bioartificial vascular grafts. Impact statement Fibrin-based bioartificial vessels represent a promising regenerative approach to generate vascular grafts with superior biocompatibility and hemocompatibility compared to currently available synthetic graft materials. Precapillarization of bioartificial vascular grafts may improve nutrition of the vessel wall and integration of the graft into the target organism's microvasculature. In native vessels, physiological vasa vasorum alignment is pivotal for proper function of the tunica adventitia. Thus, it is necessary to induce longitudinal capillary alignment in the tunica adventitia of bioengineered vessels as well to secure long-term graft patency and function. This alignment can be reliably achieved by controlled biomechanical stimulation in vitro.

Preliminary application of native Nephila edulis spider silk and fibrin implant causes granulomatous foreign body reaction in vivo in rat's spinal cord.

After spinal cord injury, gliomesenchymal scaring inhibits axonal regeneration as a physical barrier. In peripheral nerve injuries, native spider silk was shown to be an effective scaffold to facilitate axonal re-growth and nerve regeneration. This study tested a two-composite scaffold made of longitudinally oriented native spider silk containing a Haemocomplettan fibrin sheath to bridge lesions in the spinal cord and enhance axonal sprouting. In vitro cultivation of neuronal cells on spider silk and fibrin revealed no cytotoxicity of the scaffold components. When spinal cord tissue was cultured on spider silk that was reeled around a metal frame, migration of different cell types, including neurons and neural stem cells, was observed. The scaffold was implanted into spinal cord lesions of four Wistar rats to evaluate the physical stress caused on the animals and examine the bridging potential for axonal sprouting and spinal cord regeneration. However, the implantation in-vivo resulted in a granulomatous foreign body reaction. Spider silk might be responsible for the strong immune response. Thus, the immune response to native spider silk seems to be stronger in the central nervous system than it is known to be in the peripheral body complicating the application of native spider silk in spinal cord injury treatment.

A 3-Layered Bioartificial Blood Vessel with Physiological Wall Architecture Generated by Mechanical Stimulation.

The generation of cellularized bioartificial blood vessels resembling all three layers of the natural vessel wall with physiological morphology and cell alignment is a long pursued goal in vascular tissue engineering. Simultaneous culture of all three layers under physiological mechanical conditions requires highly sophisticated perfusion techniques and still today remains a key challenge. Here, three-layered bioartificial vessels based on fibrin matrices were generated using a stepwise molding technique. Adipose-derived stem cells (ASC) were differentiated to smooth muscle cells (SMC) and integrated in a compacted tubular fibrin matrix to resemble the tunica media. The tunica adventitia-equivalent containing human umbilical vein endothelial cells (HUVEC) and ASC in a low concentration fibrin matrix was molded around it. Luminal seeding with HUVEC resembled the tunica intima. Subsequently, constructs were exposed to physiological mechanical stimulation in a pulsatile bioreactor for 72 h. Compared to statically incubated controls, mechanical stimulation induced physiological cell alignment in each layer: Luminal endothelial cells showed longitudinal alignment, cells in the media-layer were aligned circumferentially and expressed characteristic SMC marker proteins. HUVEC in the adventitia-layer formed longitudinally aligned microvascular tubes resembling vasa vasorum capillaries. Thus, physiologically organized three-layered bioartificial vessels were successfully manufactured by stepwise fibrin molding with subsequent mechanical stimulation.

Vascular procedures in patients with left ventricular assist devices: single-center experience.

OBJECTIVE: A growing number of patients suffering from heart failure is living with a left ventricular assist device (LVAD) and is in the need for non-cardiac surgery. Vascular procedures due to ischemia, bleeding, or other device-related complications may be required and pose a challenge to the caregivers in terms of monitoring and management of these patients. Therefore, we reviewed our experience with LVAD patients undergoing vascular surgery. METHODS: From January 2010 until March 2017, a total of 54 vascular procedures were performed on 41 LVAD patients at our institution. Patient records were reviewed retrospectively in terms of incidence of LVAD-related complications, including thrombosis, stroke, bleeding, wound healing, and survival associated with vascular surgery. The type of surgery was recorded, as well as various clinical demographic variables. RESULTS: Vascular procedures were performed in 35 men (85.4%) and 6 women (14.6%) with LVADs. There were no perioperative strokes, device thromboses, or device malfunctions. Thirty-day mortality overall was 26.8% (eleven patients), with most patients dying within 30 days after LVAD implantation due to multi-organ failure. In 25 procedures (46.3%), a blood transfusion was necessary. CONCLUSION: Patients on LVAD support are a complex cohort with a high risk for perioperative complications. In a setting where device function and anticoagulation are monitored closely, vascular surgery in these patients is feasible with an acceptable perioperative risk.

Eight-year experience with cryopreserved arterial homografts for the in situ reconstruction of abdominal aortic infections.

OBJECTIVE: This study investigated short-term and long-term outcomes in patients with abdominal aortic infection (mycotic aneurysm, prosthetic graft infection, aortoenteric fistula) managed by total excision of the aneurysm or the infected vascular graft and in situ aortic reconstruction with a cryopreserved arterial homograft (CAH). METHODS: From January 2000 to December 2008, 110 consecutive patients underwent CAH implantation for treatment of vascular infections. In 57 (52%), in situ revascularization of the abdominal aorta with Y-prosthesis constructed from CAHs was performed. Early outcome included 30-day mortality and the levels of daily blood markers (leucocytes, C-reactive protein, and platelets) during the postsurgical 10-day period. We reported long-term survival and freedom from reoperation rates, including all indications for reoperation. RESULTS: Indications for operation were infected vascular graft in 31 patients (55%), aortodigestive fistulae in 11 (19%), nonruptured mycotic aneurysms in 4 (7%), and ruptured mycotic aneurysms of abdominal aorta in 11 (19%). In 39 of 57 patients (68%), the intraoperative specimens were positive for at least one microorganism, and Staphylococcus aureus was present in 14 (25%). In 32 patients (82%) with intraoperative specimens positive for microorganisms, there was no evidence of the intraoperatively detected microorganisms in the postoperative specimens (wound, blood culture, and drainage fluid). The peak value of leucocytes (13.7 +/- 4.4 x 10(3)/L) and C-reactive protein (200 +/- 75 mg/L) occurred on postoperative day 3. Platelets reached the lowest value on postoperative day 2 (178 +/- 67 x 10(9)/L). Median peak body temperature was 37.7 degrees +/- 0.6 degrees C. Thirty-day mortality was 9% (5 of 57 patients). Median follow-up was 36 months (range, 4-118 months); 3-year survival was 81%, and freedom from reoperation was 89%. Five patients (9%) required reoperation, in one patient each for postoperative bleeding, acute cholecystitis, homograft occlusion, homograft-duodenum fistula, and aneurysmal degeneration. No recurrence of infection was reported. CONCLUSION: These results demonstrate an encouraging outcome after cryopreserved allograft implantation for the treatment of vascular infections in the abdominal aorta. The data represent a basis for future comparisons with other treatment modalities for vascular infections, including silver-coated prostheses and autogenous femoral veins.

Complete Myogenic Differentiation of Adipogenic Stem Cells Requires Both Biochemical and Mechanical Stimulation.

Vascular tissue engineering of the middle layer of natural arteries requires contractile smooth muscle cells (SMC) which can be differentiated from adipose-derived mesenchymal stem cells (ASC) by treatment with transforming growth factor-ß, sphingosylphosphorylcholine and bone morphogenetic protein-4 (TSB). Since mechanical stimulation may support or replace TSB-driven differentiation, we investigated its effect plus TSB-treatment on SMC orientation and contractile protein expression. Tubular fibrin scaffolds with incorporated ASC or pre-differentiated SMC were exposed to pulsatile perfusion for 10 days with or without TSB. Statically incubated scaffolds served as controls. Pulsatile incubation resulted in collagen-I expression and orientation of either cell type circumferentially around the lumen as shown by alpha smooth muscle actin (αSMA), calponin and smoothelin staining as early, intermediate and late marker proteins. Semi-quantitative Westernblot analyses revealed strongly increased αSMA and calponin expression by either pulsatile (12.48-fold; p < 0.01 and 38.15-fold; p = 0.07) or static incubation plus TSB pre-treatment (8.91-fold; p < 0.05 and 37.69-fold; p < 0.05). In contrast, contractility and smoothelin expression required both mechanical and TSB stimulation since it was 2.57-fold increased (p < 0.05) only by combining pulsatile perfusion and TSB. Moreover, pre-differentiation of ASC prior to pulsatile perfusion was not necessary since it could not further increase the expression level of any marker.

Prospective evaluation of preoperative lung ultrasound for prediction of perioperative outcome and myocardial injury in adult patients undergoing vascular surgery (LUPPO study).

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a frequent perioperative event in vascular surgery, associated both with worse outcome and subsequent cardiovascular events. Current guidelines advocate troponin (hs-cTnT) and NT-proBNP measurements in selected patients before surgery, but accurate preoperative identification of patients at risk for MINS is an unmet clinical need. Focused lung ultrasound (LUS) might help to select patients at increased risk for MINS, because it can visualize B-line artifacts correlating to cardiopulmonary disease. Therefore, we investigated whether quantification of B-line artifacts improves perioperative risk predictive accuracy for MINS. METHODS: In this prospective single-center observational study, 136 consecutive open vascular surgery patients underwent conventional preoperative assessment expanded by lung ultrasound. Lung ultrasound B-lines were counted in each of 28 bilateral scan fields of the anterior and lateral chest. Improvement of risk predictive accuracy was quantified with area under receiver operating characteristic (ROC) curve analysis and net reclassification improvement (NRI). RESULTS: We included 118 patients into the final analysis. Twenty-three (19%) patients fulfilled the criteria for the primary endpoint MINS. Three or more bilateral positive B-line fields were calculated as the best ROC-derived cutoff associated with an increased incidence of MINS (odds ratio: 4.4; 95% confidence interval [CI]: 1.5 to 12.7; P=0.007). Adding LUS to hs-cTnT measurements improved risk predictive accuracy for MINS (NRI: 0.36, P=0.043). CONCLUSIONS: Lung ultrasound in combination with hs-cTnT showed a better test accuracy than hs-cTnT alone and might guide clinicians to identify vascular patients at increased risk for MINS.

Dehydration improves biomechanical strength of bioartificial vascular graft material and allows its long-term storage.

INTRODUCTION: We have recently reported about a novel technique for the generation of bioartificial vascular grafts based on the use of a compacted fibrin matrix. In this study, we evaluated the effects of a dehydration process on the biomechanical properties of compacted fibrin tubes and whether it allows for their long-term storage. MATERIALS AND METHODS: Fibrin was precipitated from fresh frozen plasma by means of cryoprecipitation and simultaneously with a thrombin solution applied in a high-speed rotating casting mold. Subsequent dehydration of the fibrin tubes (29/38) was performed in dry air with a dilator inside the tube to prevent the collapse of the lumen. Dehydrated fibrin tubes were stored for six (n=9) and 12 months (n=10) at room temperature. Comparative analysis was done on initially generated and dehydrated fibrin tubes before and after storage to evaluate the effects of the dehydration process and storage on the biomechanical properties and structure of the tubes. RESULTS: Thirty-eight fibrin tubes were generated by high-speed rotation-molding from 142±3 mg fibrinogen with an inner diameter of 5.8±0.1 mm and a length of 100 mm. A centrifugal force of nearly 900×g compacted applied fibrin, while fluid was pressed out of the matrix and drained from the mold via holes resulting in a 16-fold compaction of the fibrin matrix. Dehydration was characterized by shrinkage of the tubes to a diameter of 3.2±0.2 mm, while the length remained at 100 mm equivalent to a further two-fold compaction. The biomechanical strength of the dehydrated fibrin tubes significantly increased to values comparable to that of native ovine carotid arteries and maintained during the first 6 months of storage. After 12 months of storage, only five of 10 tubes were intact, and only one showed maintained biomechanical strength. DISCUSSION: Compaction of a fibrin matrix in high-speed rotation-moulding and subsequent dehydration enables for the construction of small-caliber fibrin grafts. Over and above, the dehydration process allows their storage and stockpiling as a prerequisite for clinical use.

Outgrowing endothelial and smooth muscle cells for tissue engineering approaches.

In recent years, circulating progenitors of endothelial cells and smooth muscle cells were identified in the peripheral blood. In our study, we evaluated the utilization of both cell types isolated and differentiated from peripheral porcine blood in terms for their use for tissue engineering purposes. By means of density gradient centrifugation, the monocyte fraction from porcine blood was separated, split, and cultivated with specific culture media with either endothelial cell growth medium-2 or smooth muscle cell growth medium-2 for the differentiation of endothelial cells or smooth muscle cells. Obtained cells were characterized at an early stage of cultivation before the first passage and a late stage (fourth passage) on the basis of the expression of the antigens CD31, CD34, CD45, nitric oxide synthase, and the contractile filaments smooth-muscle alpha-actin (sm-alpha-actin) and smoothelin. Functional characterization was done based on the secretion of nitric oxide, the formation of a coherent monolayer on polytetrafluoroethylene, and capillary sprouting. During cultivation in both endothelial cell growth medium-2 and smooth muscle cell growth medium-2, substantially two types of cells grew out: early outgrown CD45-positive cells, which disappeared during further cultivation, and in 85% (n = 17/20) of cultures cultivated with endothelial cell growth medium-2 colony-forming late outgrowth endothelial cells. During cultivation with smooth muscle cell growth medium-2 in 80% (n = 16/20) of isolations colony-forming late outgrowth smooth muscle cells entered the stage. Cultivation with either endothelial cell growth medium-2 or smooth muscle cell growth medium-2 had selective effect on the late outgrown cells to that effect that the number of CD31-positive cells increased from 34.8% ± 13% to 83.9% ± 8% in cultures cultivated with endothelial cell growth medium-2 and the number of sm-α-actin+ cells increased from 52.6% ± 18% to 88% ± 5% in cultures cultivated with smooth muscle cell growth medium-2, respectively. Functional analyses revealed significantly higher levels of nitric oxide secretion, endothelialization capacity, and capillary formation in not expanded cultures cultivated with endothelial cell growth medium-2 in comparison to later stages of cultivation and mature aortic cells. Blood seems to be a reliable and feasible source for the isolation of both endothelial and smooth muscle cells for application in tissue engineering approaches. Whereas, early co-cultures of early and late outgrowth cells provide functional advantages, the differentiation of cells can be directed selectively by the used culture medium for the expansion of highly proliferative late outgrowth endothelial cells and late outgrowth smooth muscle cells, respectively.

Novel method for the generation of tissue-engineered vascular grafts based on a highly compacted fibrin matrix.

The generation of tissue-engineered blood vessel substitutes remains an ongoing challenge for cardiovascular tissue engineering. Full biocompatibility and immediate availability have emerged as central issues for clinical use. To address these issues, we developed a technique that allows the generation of highly stable tubular fibrin segments. The process is based on the compaction of fibrin in a custom-made high-speed rotation mold. In an automated process, fibrin is precipitated from plasma by means of the Vivostat® system. Following application to the rotating mold, the fibrin was compacted by centrifugal force and excess fluid was pressed out. This compaction results in increasing cross-links between the fibrin fibrils and a corresponding significant increase of biomechanical stability up to a burst strength of 230mm of mercury. The molding process allows for a simultaneous seeding procedure. In a first in vivo evaluation in a sheep model, segments of the carotid artery were replaced by tissue-engineered vascular grafts, generated immediately prior to implantation (n=6). Following subjection to the body's remodeling mechanisms, the segments showed a high structural similarity to a native artery after explantation at 6months. Thus, this technique may represent a powerful tool for the generation of biomechanically stable vascular grafts immediately prior to implantation. STATEMENT OF SIGNIFICANCE: Fibrin has previously been shown to be suitable as a matrix for the seeding of different celltypes and for that reason was widely used as scaffold in different fields of tissue engineering. Nevertheless, fibrin's lack of stability has strongly limited its application. Our study describes a novel moulding technique for the generation of a highly compacted fibrin matrix. Using this approach, it was possible to optimize the engineering process of tubular fibrin segments to provide bioartificial vascular grafts within one hour with sufficient stability for immediate implantation in the arterial system. Thus, this technique may represent a powerful tool to get closer to the ultimate aim of an optimal bioartificial vascular graft.

[Pseudoaneuryma after transradial puncture in systemic lysis of basilar artery thrombosis]. / Pseudoaneurysma nach transradialer Punktion bei systemischer Lyse einer Basilaristhrombose.

HISTORY: Because of neurological symptoms as a result of thrombotic occlusion of the basilar artery, a successful revascularization after systemic Actilyse application was performed in a 78 year old patient. Later, it came to the formation of a pseudoaneurysm at the radial artery, punctured for invasive blood pressure measurement. TREATMENT AND COURSE: After oscillographic respectively ultrasound detection of a 2 cm wide pseudoaneurysm from the radial artery, the surgical resection of the aneurysm sac was performed. An ultrasound-guided manual compression due to the localization of a thrombus close to the aneurysm neck could not be conducted. The further clinical course was unremarkable. CONCLUSION: With an increasing number of pseudoaneurysms as a complication of transradial puncture occuring more frequently in the context of intensive care supply and rising outpatient cardiac catheterization (coronary angiography and PCI), the knowledge of care options of vascular complications are of particular importance before practical application.

Renal function interferes with copeptin in prediction of major adverse cardiac events in patients undergoing vascular surgery.

OBJECTIVE: Precise perioperative risk stratification is important in vascular surgery patients who are at high risk for major adverse cardiovascular events (MACE) peri- and postoperatively. In clinical practice, the patient's perioperative risk is predicted by various indicators, e.g. revised cardiac index (RCRI) or modifications thereof. Patients suffering from chronic kidney disease (CKD) are stratified into a higher risk category. We hypothesized that Copeptin as a novel biomarker for hemodynamic stress could help to improve the prediction of perioperative cardiovascular events in patients undergoing vascular surgery including patients with chronic kidney disease. METHODS: 477 consecutive patients undergoing abdominal aortic, peripheral arterial or carotid surgery from June 2007 to October 2012 were prospectively enrolled. Primary endpoint was 30-day postoperative major adverse cardiovascular events (MACE). RESULTS: 41 patients reached the primary endpoint, including 63.4% aortic, 26.8% carotid, and 9.8% peripheral surgeries. Linear regression analysis showed that RCRI (P< .001), pre- (P< .001), postoperative Copeptin (P< .001) and Copeptin level change (P= .001) were associated with perioperative MACE, but CKD remained independently associated with MACE and Copeptin levels. Multivariate regression showed that increased Copeptin levels added risk predictive information to the RCRI (P= .003). Especially in the intermediate RCRI categories was Copeptin significantly associated with the occurrence of MACE. (P< .05 Kruskal Wallis test). Subdivision of the study cohort into CKD stages revealed that preoperative Copeptin was significantly associated with CKD stages (P< .0001) and preoperative Copeptin measurements could not predict MACE in patients with more severe CKD stages. CONCLUSION: Preoperative Copeptin loses its risk predictive potential for perioperative MACE in patients with chronic kidney disease undergoing vascular surgery.

Unusual Case of an Arterial Thoracic Outlet Syndrome due to Srb Anomaly.

A thoracic outlet syndrome (TOS) is caused by arterial or nervous obstruction because of skeletal or muscular anomalies and hypertrophies. Congenital rib anomalies occur with low incidences (0.15-0.31%), predominantly affect the right side and are normally diagnosed at a young age or remain asymptomatic throughout life. Here, we report on the unusual case of a 71-year-old female patient with subacute ischemia of the left arm due to a TOS resulting from Srb anomaly, a very rare congenital rib anomaly.