Intimal Injury Research Articles

Balloon-based Injury to Induce Myointimal Hyperplasia in the Mouse Abdominal Aorta

The use of animal models is essential for a better understanding of MH, one major cause for arterial stenosis.In this article, we demonstrate a murine balloon denudation model, which is comparable with established vessel injury models in large animals. The aorta denudation model with balloon catheters mimics the clinical setting and leads to comparable pathobiological and physiological changes. Briefly, after performing a horizontal incision in the aorta abdominalis, a balloon catheter will be inserted into the vessel, inflated, and introduced retrogradely. Inflation of the balloon will lead to intima injury and overdistension of the vessel. After removing the catheter, the aortic incision will be closed with single stiches. The model shown in this article is reproducible, easy to perform, and can be established quickly and reliably. It is especially suitable for evaluating expensive experimental therapeutic agents, which can be applied in an economical fashion. By using different knockout-mouse strains, the impact of different genes on MH development can be assessed.

Balloon-based Injury to Induce Myointimal Hyperplasia in the Mouse Abdominal Aorta

The use of animal models is essential for a better understanding of MH, one major cause for arterial stenosis.In this article, we demonstrate a murine balloon denudation model, which is comparable with established vessel injury models in large animals. The aorta denudation model with balloon catheters mimics the clinical setting and leads to comparable pathobiological and physiological changes. Briefly, after performing a horizontal incision in the aorta abdominalis, a balloon catheter will be inserted into the vessel, inflated, and introduced retrogradely. Inflation of the balloon will lead to intima injury and overdistension of the vessel. After removing the catheter, the aortic incision will be closed with single stiches. The model shown in this article is reproducible, easy to perform, and can be established quickly and reliably. It is especially suitable for evaluating expensive experimental therapeutic agents, which can be applied in an economical fashion. By using different knockout-mouse strains, the impact of different genes on MH development can be assessed.

Modified candy-plug device for aneurysmal false lumen occlusion in chronic type B aortic dissection

Modified candy-plug device for aneurysmal false lumen occlusion in chronic type B aortic dissection

WWC3 inhibits intimal proliferation following vascular injury via the Hippo signaling pathway.

The Hippo signaling pathway is involved in the formation and development of the cardiovascular system. In the present study, the effects of WWC family member 3 (WWC3) on vascular smooth muscle cells (VSMCs) following injury were investigated, in addition to the associated mechanisms underlying this process. Platelet-derived growth factor BB (PDGF-BB) was used as a cell injury factor, and rats with balloon injuries were used as a model of carotid intimal injury. Furthermore, the expression levels of WWC3 in VSMCs and arteries post-injury were investigated, in addition to the effect of WWC3 on the proliferation and migration of VSMCs. The results demonstrated that following injury, WWC3 expression was suppressed in VSMCs and the rat carotid artery, and the activity of the Hippo signaling pathway was significantly downregulated. In addition, the expression of YY1-associated protein-1 (YAP) and a number of its downstream target genes, including connective tissue growth factor (CTGF), were enhanced, thus enhancing the proliferation and migration of VSMCs. Knockdown of WWC3 suppressed the levels of large tumor suppressor kinase 1 (LATS1) expression and YAP phosphorylation, and the expression of YAP, CTGF and cyclin E was subsequently enhanced, thus promoting cell proliferation and migration. Similar results were obtained following overexpression of WWC3. Treatment with PDGF-BB was revealed to suppress the proliferation and migration of VSMCs transfected with the WWC3 plasmid, compared with VSMCs transfected with an empty vector. The present study demonstrated that WWC3 may interact with LATS1 in order to upregulate the Hippo signaling pathway via co-immunoprecipitation and enhancement of the phosphorylation of LATS1, in addition to the corresponding suppression of the nuclear import of YAP. However, VSMCs transfected with WWC3 plasmid with a deletion of the WW domain fail to exhibit this effect. These results suggested that WWC3 expression is downregulated in VSMCs during neointimal hyperplasia following injury (PDGF-BB stimulation or balloon injury). WWC3 upregulates the activity of the Hippo signaling pathway, and weakens the proliferation and migration of VSMCs. Furthermore, the results of the present study suggested that WWC3 may interact with LATS1 to promote the phosphorylation of YAP and reduce its nuclear translocation, upregulate the activity of the Hippo pathway, and suppress the proliferation and migration of VSMCs following injury.

A Rare and Dangerous Complication of Central Venous Catheterization: Intimal Injury

A Rare and Dangerous Complication of Central Venous Catheterization: Intimal Injury

Damage effect of Solitaire stent on tunica intima during thrombectomy

Objective To discuss the damage effect of Solitaire stent on tunica intima during thrombectomy, so as to evaluate the safety of thrombectomy. Methods Twelve healthy male New Zealand rabbits were randomly divided into 4 groups (3 rabbits in each group), including control group and 3 thrombectomy groups. Microcatheter was used instead of stent in control group. The other 3 groups underwent mimic thrombectomy for 1, 3 and 5 times in the same position, respectively. The procedure was performed at both sides of carotid artery of each rabbit. Immediately after operation, bilateral carotid arteries of each rabbit were removed, performed HE staining and examined the ultrastructure under microscope. Semi?quantitative analysis was used to evaluate the damage of carotid artery. Results During the model preparation, DSA showed the diameter of vascular wall was 2.10-2.90 mm, and there was no vascular spasm, bleeding, perforation or arterial dissection. Therefore, the model was successfully established. The difference of carotid artery damage among different groups was statistically significant ( F = 119.108, P = 0.000). Compared with control group, the carotid artery damage of 3 thrombectomy groups was more serious ( q = 3.136, P = 0.001; q = 7.463, P = 0.000; q = 10.682, P = 0.000). The carotid artery damage of the second and third thrombectomy group was more serious than the first group ( q = 3.330, P = 0.000; q = 8.160, P = 0.000). The carotid artery damage of the third thrombectomy group was more serious than the second group ( q = 4.830, P = 0.000). Optical microscope observation showed that with the increase of times of thrombectomy, carotid intimal injury was more extensive and intimal reaction was more severe. Scanning electron microscopy showed that with the increase of times of thrombectomy, the degree of carotid artery injury was increased. Conclusions Solitaire stent may injure tunica intima, and with the increase of times of thrombectomy, the damage to vascular wall will increase. DOI: 10.3969/j.issn.1672-6731.2017.11.008

WITHDRAWN: Intimal injury of abdominal aorta following traumatic spondylolisthesis in a polytrauma patient-a case report

WITHDRAWN: Intimal injury of abdominal aorta following traumatic spondylolisthesis in a polytrauma patient-a case report

GW28-e1062 WWC3 inhibits intimal proliferation after vascular injury through Hippo signaling pathway

To investigate the effect of WWC3 on vascular smooth muscle cells (VSMCs) after injury and its possible mechanism. We used platelet-derived growth factor BB (PDGF-BB) as cell injury, rats with balloon injury to make model of rat carotid artery intima injury. Detect the expression of WWC3 in A10

ENDOSCOPIC RADIAL ARTERY HARVEST--OUTCOMES AND LESSONS LEARNED AFTER 1000 HARVESTS

Endoscopic radial artery harvest (ERAH) for coronary artery bypass grafting (CABG) offers the potential for decreased pain, infection, neurological complications of the arm with dramatically improved cosmesis compared to an open/conventional harvest. Because of these potential benefits and our experience with endoscopic saphenous vein harvest (ESVH), we adopted ERAH as standard of care for CABG patients at our institution. Here we present our experience and outcomes with this technique after more than 1000 harvests. From July 2004 to present, our centre performed endoscopic radial artery harvest (ERAH) in 1003 patients. We adapted a reusable ESVH system (Karl Storz Endoscopy) with the addition of a harmonic ultrasonic scalpel/shears (Ethicon Endosurgery) to facilitate the removal of the radial artery (RA) for use in our CABG patients. Data was collected prospectively regarding harvest technique (harvest times, graft length, incision length, histology) and patient outcomes (infection, cosmesis, hematomas, gross neurological impairment, patient satisfaction and all MACE’s). Thirty-two patients underwent angiographic assessment of their RA grafts at >5 years. RA Harvest times ranged from 21-125 minutes with a median harvest time of 37min +/- 4 in the first quartile of our series and greatly decreased with experience. Average length of artery extracted was 17.2 cm +/- 1.2 cm through a mean incision length of 2.3 cm +/- 0.7cm. All RA grafts harvested were deemed suitable for grafting. Six patients were converted to open harvest and 15 patients required the addition of a second proximal arm incision. There were 17 ERAH wound infections (1.7%). Neurological impairments were infrequent and mostly consisted of transient numbness over the thenar eminence, index finger and lateral forearm. Five patients manifested clinically significant chronic neuralgias post-operatively. Histological examination of multiple samples of harvested RA’s revealed no signs of intimal trauma or thermal injury. There were no clinically significant hematomas post-operatively and no arm required operative re- intervention. There were 7 postoperative deaths (0.7%), 12 post-op MI’s (1.2%), 22 central neurological complications (2.2%) and no cases of renal failure requiring dialysis. Long-term follow-up on angiography and CT/Angiography revealed a patency rate of 91.3%. ERAH can be effectively and safely adopted as a harvest technique for the RA for CABG. Our results demonstrate ERAH provides adequate length conduits in a timely manner through much smaller incisions, resulting in low rates of infection, neurological impairment, excellent long-term patency and no evidence of histological damage.

Acute thrombus formation on phosphorilcholine surface modified flow diverters

PurposeThromboembolic complications remain a limitation of flow diverting stents. We hypothesize that phosphorilcholine surface modified flow diverters (Pipeline Flex with Shield Technology, sPED) would have less acute thrombus formation on...

CORR Insights®: Venous Thromboembolism Prophylaxis After TKA: Aspirin, Warfarin, Enoxaparin, or Factor Xa Inhibitors?

CORR Insights®: Venous Thromboembolism Prophylaxis After TKA: Aspirin, Warfarin, Enoxaparin, or Factor Xa Inhibitors?

Flow Perturbation Mediates Neutrophil Recruitment and Potentiates Endothelial Injury via TLR2 in Mice: Implications for Superficial Erosion.

Superficial erosion currently causes up to a third of acute coronary syndromes; yet, we lack understanding of its mechanisms. Thrombi because of superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation. This study tested in vivo the involvement of disturbed flow and of neutrophils, hyaluronan, and Toll-like receptor 2 ligation in superficial intimal injury, a process implicated in superficial erosion. In mouse carotid arteries with established intimal lesions tailored to resemble the substrate of human eroded plaques, acute flow perturbation promoted downstream endothelial cell activation, neutrophil accumulation, endothelial cell death and desquamation, and mural thrombosis. Neutrophil loss-of-function limited these findings. Toll-like receptor 2 agonism activated luminal endothelial cells, and deficiency of this innate immune receptor decreased intimal neutrophil adherence in regions of local flow disturbance, reducing endothelial cell injury and local thrombosis (P<0.05). These results implicate flow disturbance, neutrophils, and Toll-like receptor 2 signaling as mechanisms that contribute to superficial erosion, a cause of acute coronary syndrome of likely growing importance in the statin era.

Inhibition effect of tacrolimus and platelet-derived growth factor-BB on restenosis after vascular intimal injury

Excessive proliferation and migration of vascular smooth muscle cells(VSMCs) and delayed proliferation and migration of endothelial cells(ECs) were the main cause of restenosis after endovascular interventional therapy. Since tacrolimus has proved to be more sensitive to inhibiting VSMCs’ proliferation,and platelet-derived growth factor-BB(PDGF-BB) benefitted ECs’ and VSMCs’ proliferation, this study was aimed to identify combined effect of tacrolimus and PDGF-BB, investigate any mechanisms underneath and demonstrate combined effect of two drugs in vivo. As the results showed we confirmed differential effect of PDGF-BB and tacrolimus on ECs and VSMCs. On the concentration level of 2–5μg/ml tacrolimus plus 10ng/ml PDGF-BB, combination of drugs could effectively promote ECs proliferation and migration, and meanwhile inhibit VSMCs proliferation and migration, and the inhibition of p-mTOR’s expression within VSMCs played an important role in this differentiated effect. Raising concentration level of PDGF-BB would weaken inhibitory effect of tacrolimus on both kinds of cell. For injured intima, the mix solution of two drugs could promote intima healing and suppress excessive intimal hyperplasia.

Imaging of Vascular Injuries of the Extremities.

Multidetector computed tomography angiography (MDCTA) of the upper and lower extremities is the standard of care in the assessment of trauma patients with vascular trauma of the upper and lower extremities. A MDCTA of the extremities is typically integrated into multiphasic whole-body computed tomography trauma protocols in patients with suspected vascular injury. MDCTA has replaced catheter-directed digital subtraction angiography (DSA) as the modality of choice for the initial detection and characterization of vascular injuries because it is readily available, noninvasive, and faster than DSA. Understanding the imaging findings and pitfalls of upper and lower extremity MDCTA is essential in the diagnosis of vascular injuries such as active hemorrhage, vasospasm and stenosis, hematoma, occlusion and thrombosis, posttraumatic arteriovenous fistula, pseudoaneurysm, and patterns of intimal injury including dissection. We discuss the diagnosis and characterization of vascular injuries of the upper and lower extremities using MDCTA including derived multiplanar reconstructions, maximum intensity projection, and three-dimensional volume rendering techniques.

Efficacy of endovascular interventional minimally invasive techniques in treatment of acute brachial artery injury

Objective To evaluate the efficacy of endovascular interventional minimally invasive techniques in treatment of acute brachial artery injury. Methods A retrospective case series study was designed to analyzed data of 16 cases (11 males and 5 females) sustaining acute brachial artery injury treated from March 2011 to August 2016. Mean age was 47.9 years (range, 27-66 years). Left upper extremity vascular injury occurred in 7 cases and right upper extremity vascular injury occurred in 9. There were 13 cases of arterial intima injury and 3 of arterial pseudoaneurysm. All patients underwent endovascular therapy including stent implantation and balloon dilatation. Angiography was used to evaluate the repair of brachial artery and the operation time was recorded. Improvements of distal limb arterial pulse and limb ischemic symptoms were observed, and the patients who were followed up with stent lumen stenosis more than 50% received endovascular treatment again. Results The procedures was successful in all patients, with operation time of 30-75 minutes (mean, 45 minutes). After the insertion of a stent, recovered brachial artery blood flow and disappeared pseudoaneurysm were observed on angiography, without occurrence of stent stenosis or contrast extravasation. Symptoms of local pain and numbness were alleviated, and blood supply of the distal brachial artery was improved after operation. All patients were followed up for 3-36 months(mean, 16.7 months). The false aneurysm did not recur. Two cases of stent stenosis more than 50% had a second balloon dilation procedure and the blood flow returned to normal. Stent patency was found in 14 cases with stent stenosis of less than 50%. During the follow-up period, no ischemic necrosis, displacement of the stent or stent fracture were found. Conclusion For acute brachial artery injury, endovascular management exhibits higher technical success rate and good clinical outcome with a low incidence of complications. Key words: Brachial artery; Stents; Vascular system injuries

Reduction of the risk of thrombosis and restenosis with negatively charged electret covered stents

Rationale : Endovascular implantation may lead to mechanical injury of the vessel walls, their inflammation and subsequent formation of a thrombus in the stented portion of the vessel, as well as to endothelial growth and restenosis. Intimal injury changes the potential of the damaged area from negative to positive. Aim : To demonstrate the efficacy of corrective negative charge on the stent surface after its endovascular implantation in the reduction of the risk of vessel thrombosis and restenosis. Materials and methods : With a terminal element technique we created a model for distribution of electrostatic potentials in a healthy and in a partially injured vessel, as well as in a vessel with a negatively charged electret stent. Trials of experimental and serial stents in animals were performed with stent placement into the pig neck arteries with subsequent (at day 21) histological examination of the areas of stent placement. Morphological abnormalities and vessel wall reactions after endovascular carotid stent implantation, such as clot formation and endothelial reaction were assessed. Results : Negatively charged electret cover of the stent produces corrective electrostatic field to prevent thrombus formation and vascular intima reaction with subsequent restenosis. The use of the stent with negatively charged electret cover ensures a significant reduction of the risk for positive potential inside the injured vessel, thereby dramatically reducing the risk of vessel thrombosis and restenosis. After placement of stents with negatively charged electret cover to animals, there was very mild proliferation of endothelial cells of the vessel wall neointima, compared to that after placement of the reference stents; no thrombus formation was observed. If the reference uncovered stents were placed, there was a dramatic narrowing of the arterial lumen due to proliferation of endothelial neointimal cells, as well as full thrombotic closure of the vessel. Conclusion : The suggested technology allows for improvement of endovascular stent placement, for reduction of the risk of thrombosis and restenosis after endovascular interventions aimed at revascularization of arterial stenosis.

Utilization of Intravascular Ultrasound for the Evaluation and Management of Lower Extremity Malperfusion in a Type B Aortic Dissection

Aortic dissection (AD) is a pathologic entity initiated from a tear in the intimal layer that allows blood flow between the intima and media, resulting in a separation of these layers into a true and false lumen. Subsequently, this flow within the false lumen encroaches on the true lumen flow and may cause malperfusion to vital organs or aortic rupture. On the basis of the anatomical location of the intimal tear, clinical presentation management may differ significantly. AD is classified as Stanford Type A or B based on the location of the intimal injury. In Stanford Type A, the site of injury is at the aortic root, which requires urgent surgical therapy. Type B are dissections that occur at or just distal to the takeoff of the left subclavian artery and in many situations can be managed medically by reduction in blood pressure.1 , 2In type B dissections that fail medical management or develop malperfusion, endovascular treatment has been used and described.3It provides a minimal invasive method; however, there are cases that may require open or a hybrid approach.3 , 4

Form and Size Matter: Increased Risk of Thrombosis in Microvessels with Surgically Created Endothelial Lesions.

Background Atherosclerosis is a known risk factor for flap loss in microsurgery. Several microsurgical techniques, like plaque removal, have been proposed for atherosclerotic vessels, but these techniques often induce intimal injuries. The aim of this study was to investigate the impact of various endothelial defects on the risk of thrombosis in a rat acute intimal injury model. Methods Endothelial defects of various forms and sizes were created in the abdominal aorta of 30 male Wistar rats following a strict protocol. Defect sizes were measured and classified as round, horizontal, or vertical based on their configuration. An hour after reestablishing the blood flow, the abdominal aorta was harvested and the operation site was assessed for signs of thrombosis clinically and using light microscopy. Univariate and multiple linear regression analysis were performed to identify possible influencing factors on thrombosis. Results The mean defect size was 2.65 ± 1.19 mm2. Intimal lesions were classified as round in 36.7%, horizontal in 33.3%, and vertical in 30% of specimens. Thrombus formation was detected in 46.7% clinically and in 50% histologically. Univariate regression analysis revealed that defect size (p = 0.048) and vertical form (p = 0.017) were significantly associated with thrombus formation. Multiple regression analysis corroborated vertical defects as a risk factor for thrombosis (p = 0.03). Conclusion Endothelial injuries are associated with a high risk of thrombosis with highest risks associated with vertical defects. Arteries should be carefully examined for intimal defects before microvascular anastomosis, especially in the atherosclerotic patient.

Vascular Injury in Orthopedic Trauma.

Vascular injury in orthopedic trauma is challenging. The risk to life and limb can be high, and clinical signs initially can be subtle. Recognition and management should be a critical skill for every orthopedic surgeon. There are 5 types of vascular injury: intimal injury (flaps, disruptions, or subintimal/intramural hematomas), complete wall defects with pseudoaneurysms or hemorrhage, complete transections with hemorrhage or occlusion, arteriovenous fistulas, and spasm. Intimal defects and subintimal hematomas with possible secondary occlusion are most commonly associated with blunt trauma, whereas wall defects, complete transections, and arteriovenous fistulas usually occur with penetrating trauma. Spasm can occur after either blunt or penetrating trauma to an extremity and is more common in young patients. Clinical presentation of vascular injury may not be straightforward. Physical examination can be misleading or initially unimpressive; a normal pulse examination may be present in 5% to 15% of patients with vascular injury. Detection and treatment of vascular injuries should take place within the context of the overall resuscitation of the patient according to the established principles of the Advanced Trauma Life Support (ATLS) protocols. Advances in the field, made mostly during times of war, have made limb salvage the rule rather than the exception. Teamwork, familiarity with the often subtle signs of vascular injuries, a high index of suspicion, effective communication, appropriate use of imaging modalities, sound knowledge of relevant technique, and sequence of surgical repairs are among the essential factors that will lead to a successful outcome. This article provides a comprehensive literature review on a subject that generates significant controversy and confusion among clinicians involved in the care of trauma patients. [Orthopedics. 2016; 39(4):249-259.].

AJKD Atlas of Renal Pathology: Systemic Sclerosis

Systemic sclerosis (scleroderma) has a strong predilection in women, with onset typically between ages 30-50 years. Scleroderma kidney disease occurs in 60%-70% of patients with systemic scleroderma, mostly in those with a diffuse, rather than limited, form of cutaneous scleroderma. Kidney disease is evident by hypertension, proteinuria, and loss of glomerular filtration rate. Scleroderma kidney crisis develops in about 10%-20%, and presents as new onset malignant hypertension with acute kidney injury. Antinuclear antibody is positive in >90% of these patients. Anti-topoisomerase 1 and anti-RNA polymerase antibodies are often associated with kidney involvement. Patients with scleroderma kidney crisis may require dialysis. Use of angiotensin-converting enzyme inhibitors has improved prognosis of patients with kidney crisis, but mortality at 5 years remained at 30%-40%. Light microscopy: Medium- and large-sized arteries are affected by thrombotic microangiopathy. Fibrin thrombi with fibrinoid necrosis of the vessel wall without associated wall inflammation are characteristic. Intimal mucoid change, endothelial swelling, and fragmented red blood cells within the vessel wall occur acutely. Later, there is intimal proliferation, resulting in an “onion skin” concentric appearance with luminal narrowing. Glomeruli typically show ischemic collapse, but may also have mesangiolysis and fibrin thrombi. Glomerular basement membrane duplication is present in chronic cases. Tubular injury occurs with acute injury, and tubular atrophy and interstitial fibrosis are proportional to vascular injury in the chronic stages. Immunofluorescence microscopy: Nonspecific staining for immunoglobulin M and C3 may be seen. Fibrinogen staining can be observed in glomeruli and arteries associated with fibrinoid necrosis or acute thrombotic microangiopathy. Electron microscopy: Endothelial swelling and expansion of lamina rara interna are present. Glomerular basement membrane duplication with cellular interposition is present in chronic stages. Injury from scleroderma is related to endothelial injury of uncertain etiology. About half of patients have anti-endothelial antibodies. Endothelial injury leads to altered vascular permeability and platelet aggregation. Increased renin production exacerbates hypertension. Thrombotic microangiopathy of other causes has similar morphologic findings, including malignant hypertension, drug etiology, complement dysregulation, hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP), and transplant rejection. Scleroderma mostly affects interlobular arteries in contrast to HUS/TTP, which predominantly affects glomeruli. Malignant hypertension-associated thrombotic microangiopathy may have an identical appearance to that seen in scleroderma, although this is more often associated with underlying arterionephrosclerosis. Clinical history and serologic data help to distinguish these etiologies. •Fibrin thrombi with fibrinoid necrosis, mostly in interlobular arteries•Interlobular arteries with “onion skin” concentric appearance with luminal narrowing in chronic stage•Endothelial injury by electron microscopyFigure 2Scleroderma with artery showing early organization with “onion skin” change caused by lamellation and mucoid change with swelling of the intimal layer. There is corrugation of the glomerular basement membrane (Jones silver stain).Reproduced with permission from AJKD 34(2):e4.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Scleroderma with early arterial changes with swollen endothelium and mucoid appearance of the subintima with red blood cell fragments (Jones silver stain).Reproduced with permission from AJKD 34(2):e4.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 4Scleroderma in a chronic stage with fibrous organization of intimal injury resulting in a lamellated “onion skin” appearance of arteries (periodic acid–Schiff stain).Reproduced with permission from AJKD 34(2):e4.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 5Scleroderma with corrugation and expansion of the lamina rara interna, evidence of endothelial injury and ischemia (electron microscopy).Reproduced with permission from AJKD 34(2):e4.View Large Image Figure ViewerDownload Hi-res image Download (PPT)