Apoptosis, proliferation, and morphology during vein graft remodeling in rabbits.

Neo-intima development and atherosclerosis limit the long-term use of vein grafts for revascularization of ischemic tissues. Recently, studies have confirmed that proliferating cell nuclear antigen (PCNA) plays an important role in cell proliferation. Our research confirmed that 28 days after vein transplantation, PCNA expression increases significantly. Using rabbits, rather than rodents, for a more representative model of human vein grafts, we aimed to establish a time course of changes in cell proliferation and apoptosis using morphometric and immunohistochemical analyses, western blot, terminal deoxynucleotidyl transferase dUTP nick end labeling, and transmission electron microscopy (TEM). The external jugular veins of 42 healthy purebred male New Zealand white rabbits were grafted onto their common carotid arteries. The rabbits were divided into seven groups, with vein grafts being harvested before surgery, and at 1, 3, 7, 14, 28, and 90 days afterwards. The extent of stenosis and apoptosis, PCNA protein levels, and TEM morphology were subsequently examined. Intimal thickness was slightly decreased 1 day following surgery, but then increased continuously until the 90th day. Western blot and immunohistochemistry both indicated lowered PCNA expression on day 1, although levels subsequently increased, peaking at 7 days post-surgery. After surgery, apoptosis was lowest on day 7, and remained low thereafter. TEM revealed signs of apoptosis as vein graft restenosis progressed. Proliferation and apoptosis co-occurred following grafting, indicating that both processes were involved in vein graft remodeling. Apoptosis levels were highest between days 1 and 3 after surgery, whereas proliferation culminated on the 7th day.

In vivo nanoparticle assessment of pathological endothelium predicts the development of inflow stenosis in murine arteriovenous fistula.

OBJECTIVE: In vivo assessment of pathological endothelium within arteriovenous fistula (AVF) could provide new insights into inflow stenosis, a common cause of AVF primary failure in end-stage renal disease patients. Here we developed nanoparticle-based imaging strategies to assess pathological endothelium in vivo and elucidate its relationship to neointimal hyperplasia formation in AVF. APPROACH AND RESULTS: Jugular-carotid AVFs were created in C57BL/6 mice (n=38). Pathological endothelium in the AVF was visualized and quantified in vivo using dextranated magnetofluorescent nanoparticles (CLIO-VT680 [cross-linked iron oxide-VivoTag680]). At day 14, CLIO-VT680 was deposited in AVF, but only minimally in sham-operated arteries. Transmission electron microscopy revealed that CLIO-VT680 resided within endothelial cells and in the intimal extracellular space. Endothelial cells of AVF, but not control arteries, expressed vascular cell adhesion molecule-1 and showed augmented endothelial permeability near the anastomosis. Intravital microscopy demonstrated that CLIO-VT680 deposited most intensely near the AVF anastomosis (P<0.0001). The day 14 intravital microscopy CLIO-VT680 signal predicted the subsequent site and magnitude of AVF neointimal hyperplasia at day 42 (r=0.58, P<0.05). CLIO-VT680 deposition in AVF was further visualized by ex vivo MRI. CONCLUSIONS: AVF develop a pathological endothelial response that can be assessed in vivo via nanoparticle-enhanced imaging. AVF endothelium is activated and exhibits augmented permeability, offering a targeting mechanism for nanoparticle deposition and retention in pathological endothelium. The in vivo AVF nanoparticle signal identified and predicted subsequent inflow neointimal hyperplasia. This approach could be used to test therapeutic interventions aiming to restore endothelial health and to decrease early AVF failure caused by inflow stenosis.

Ultrastructure of internal jugular vein defective valves.

OBJECTIVES: To study the ultrastructure of intraluminal defects found in the internal jugular vein by using a scanning electron microscopy. METHODS: Using a scanning electron microscopy, intraluminal septa and/or defective valves blocking the flow in the distal internal jugular vein of seven patients were studied together with the adjacent wall and compared with control specimen. RESULTS: The internal jugular veins' wall showed a significant derangement of the endothelial layer as compared to controls. Surprisingly, no endothelial cells were found in the defective cusps, and the surface of the structure is covered by a fibro-reticular lamina. CONCLUSIONS: Although the lack of endothelial cells in the internal jugular vein intraluminal obstacles is a further abnormality found in course of chronic cerebrospinal venous insufficiency, our investigation cannot clarify whether this finding is primary or caused by progressive loss of endothelium in relation to altered haemodynamic forces and/or to a past post-thrombotic/inflammatory remodelling.

Establishment of an animal model of vascular restenosis with bilateral carotid artery grafting.

BACKGROUND: Vascular restenosis occurring after CABG is a major clinical problem that needs to be addressed. Vein grafts are associated with a higher degree of stenosis than artery grafts. However, the mechanism responsible for this effect has not been elucidated. We aimed to establish a rabbit model of vascular restenosis after bilateral carotid artery grafting, and to investigate the associated spatiotemporal changes of intimal hyperplasia in carotid artery and jugular vein grafts after surgery. MATERIAL AND METHODS: Twenty adult New Zealand white rabbits (10 males; 10 females), weighing 2.0-2.5 kg, were obtained from the Experimental Animal Center of Southern Medical University, Guangzhou, China (License No.: scxk-Guangdong-2006-0015). We quantitatively analyzed intimal thickness, area, and degree of stenosis in carotid artery and jugular vein bridges. RESULTS: After 8 weeks of a high-fat diet, rabbit carotid arteries showed early atherosclerotic lesions. With increasing time after surgery, carotid artery and jugular vein grafts showed histopathological and morphological changes, including smooth muscle cell migration, lipid deposition, intimal hyperplasia, and vascular stenosis. The degree of vascular stenosis was significantly higher in vein grafts than in artery grafts at all time points - 35.1±6.7% vs. 16.1±2.6% at Week 12, 56.2±8.5% vs. 23.4±3.4% at Week 16, and 71.2±1.3% vs. 25.2±5.3% at Week 20. CONCLUSIONS: Rabbit bilateral carotid arteries were grafted with carotid artery and jugular vein bridges to simulate pathophysiological processes that occur in people after CABG surgery.

Is a swine model of arteriovenous malformation suitable for human extracranial arteriovenous malformation? A preliminary study.

OBJECTIVE: A chronic arteriovenous malformation (AVM) model using the swine retia mirabilia (RMB) was developed and compared with the human extracranial AVM (EAVM) both in hemodynamics and pathology, to see if this brain AVM model can be used as an EAVM model. METHODS: We created an arteriovenous fistula between the common carotid artery and the external jugular vein in eight animals by using end-to-end anastomosis. All animals were sacrificed 1 month after surgery, and the bilateral retia were obtained at autopsy and performed hematoxylin and eosin staining and immunohistochemistry. Pre- and postsurgical hemodynamic evaluations also were conducted. Then, the blood flow and histological changes of the animal model were compared with human EAVM. RESULTS: The angiography after operation showed that the blood flow, like human EAVM, flowed from the feeding artery, via the nidus, drained to the draining vein. Microscopic examination showed dilated lumina and disrupted internal elastic lamina in both RMB of model and nidus of human EAVM, but the thickness of vessel wall had significant difference. Immunohistochemical reactivity for smooth muscle actin, angiopoietin 1, and angiopoietin 2 were similar in chronic model nidus microvessels and human EAVM, whereas vascular endothelial growth factor was significant difference between human EAVM and RMB of model. CONCLUSIONS: The AVM model described here is similar to human EAVM in hemodynamics and immunohistochemical features, but there are still some differences in anatomy and pathogenetic mechanism. Further study is needed to evaluate the applicability and efficacy of this model.

Relationship between positive end-expiratory pressure and internal jugular vein cross-sectional area.

BACKGROUND: Application of positive end-expiratory pressure (PEEP) has been used to increase the cross-sectional area (CSA) of the right internal jugular vein (IJV) in order to facilitate catheterisation. We aimed to determine the PEEP level at which the maximum increase of CSA occurred. METHODS: We enrolled 60 American Society of Anesthesiologists physical status I and II patients undergoing general endotracheal anaesthesia. The CSA was measured in the supine position with no PEEP (control condition, P0) and after applying five different PEEPs in random order: 3 (P3), 6 (P6), 9 (P9), 12 (P12), and 15 (P15) cm H(2) O. Ultrasound was used to measure and record the CSA of the right IJV at the level of the cricoid cartilage. RESULTS: All PEEP levels increased the CSA of the right IJV relative to the control (all P < 0.05). On average, P3, P6, P9, P12, and P15 increased the CSA by 21.5, 37.4, 51.9, 66.5, and 72.4%, respectively. There was no significant increase in CSA above a PEEP of 12 cm H(2) O. CONCLUSION: The application of PEEP effectively increases the CSA of the right IJV. The PEEP giving the largest CSA is 12 cm H(2) O.

Extra- and transcranial echo colour Doppler in the diagnosis of chronic cerebrospinal venous insufficiency.

A new venous disorder, chronic cerebrospinal venous insufficiency (CCSVI), has been proposed in patients with multiple sclerosis (MS). It is a vascular condition characterized by an impaired cerebrospinal venous drainage due to obstructions in the main extracranial cerebrovenous outflow routes (i.e. internal jugular veins [IJV] and/or azygos veins). In this review, the studies which assessed the prevalence of CCSVI in MS by echo colour Doppler (ECD) will be discussed. The technical aspects of determination of the five CCSVI criteria: (1) reflux in the IJV and/or vertebral veins in supine and upright position, (2) reflux in the deep cerebral veins, (3) high-resolution B-mode proximal IJV stenosis, (4) flow not Doppler detectable in IJVs and/or vertebral veins (VVs) and (5) reverted postural control of the main cerebrovenous outflow pathway are described in detail. We conclude that so far there are many studies with contradictory results, and as yet a strong scientific base to support the evidence for a causative relationship of CCSVI and MS is lacking. Recent studies call into question the validity of using ECD as a proper and reliable test for the diagnosis of CCSVI. One explanation for the variety in interpretation of the individual CCSVI criteria, with the wide-ranging percentages CCSVI, could be the different methods by using ECD to determine various criteria.

Rapamycin-loaded nanoparticles for inhibition of neointimal hyperplasia in experimental vein grafts.

BACKGROUND: Nanoparticles possess several advantages as a carrier system for intracellular delivery of therapeutic agents. Rapamycin is an immunosuppressive agent which also exhibits marked antiproliferative properties. We investigated whether rapamycin-loaded nanoparticles(NPs) can reduce neointima formation in a rat model of vein graft disease. METHODS: Poly(lactic-co-glycolic acid) (PLGA) NPs containing rapamycin was prepared using an oil/water solvent evaporation technique. Nanoparticle size and morphology were determined by dynamic light scattering methodology and electron microscopy. In vitro cytotoxicity of blank, rapamycin-loaded PLGA (RPLGA) NPs was studied using MTT Assay. Excised rat jugular vein was treated ex vivo with blank-NPs, or rapamycin-loaded NPs, then interposed back into the carotid artery position using a cuff technique. Grafts were harvested at 21 days and underwent morphometric analysis as well as immunohistochemical analysis. RESULTS: Rapamycin was efficiently loaded in PLGA nanoparticles with an encapsulation efficiency was 87.6%. The average diameter of NPs was 180.3 nm. The NPs-containing rapamycin at 1 ng/ml significantly inhibited vascular smooth muscular cells proliferation. Measurement of rapamycin levels in vein grafts shown that the concentration of rapamycin in vein grafts at 3 weeks after grafting were 0.9 ± 0.1 µg/g. In grafted veins without treatment intima-media thickness was 300.4 ± 181.5 µm after grafting 21 days. Whereas, Veins treated with rapamycin-loaded NPs showed a reduction of intimal-media thickness of 150.2 ± 62.5 µm (p = 0.001). CD-31 staining was used to measure luminal endothelial coverage in grafts and indicated a high level of endothelialization in 21 days vein grafts with no significant effect of blank or rapamycin-loaded NPs group. CONCLUSIONS: We conclude that sustained-release rapamycin from rapymycin loaded NPs inhibits vein graft thickening without affecting the reendothelialization in rat carotid vein-to-artery interposition grafts and this may be a promising therapy for the treatment of vein graft disease.

The impact of Trendelenburg position and positive end-expiratory pressure on the internal jugular cross-sectional area.

BACKGROUND: Increasing the cross-sectional area (CSA) of the right internal jugular vein facilitates cannulation and decreases complications. Maneuvers such as the Trendelenburg tilt position and ventilation with a positive end-expiratory pressure (PEEP) may increase the CSA of the right internal jugular vein. We determined the changes in the CSA in response to different maneuvers. METHODS: The CSA (cm(2)) of the right internal jugular vein was assessed in 50 anesthetized adult cardiothoracic surgery patients using 2-dimensional ultrasound. First, the CSA was measured in response to supine position with no PEEP (control condition, S0) and compared with 5 different randomly ordered maneuvers: (1) PEEP ventilation with 5 cm H(2)O (S5), (2) PEEP with 10 cm H(2)O (S10), (3) a 20 degrees Trendelenburg tilt position with a PEEP of 0 cm H(2)O (T0), (4) a 20 degrees Trendelenburg tilt position combined with a PEEP of 5 cm H(2)O (T5), and (5) a 20 degrees Trendelenburg tilt position combined with a PEEP of 10 cm H(2)O (T10). RESULTS: All maneuvers increased the CSA of the right internal jugular vein with respect to the control condition S0 (all P < 0.05). S5 increased the CSA on average by 15.9%, S10 by 22.3%, T0 by 39.4%, T5 by 38.7%, and T10 by 49.7%. CONCLUSION: In a comparison of the effectiveness of applying different PEEP levels and/or the Trendelenburg tilt position on the CSA of the right internal jugular vein, the Trendelenburg tilt position was most effective.

Apoptosis, cell proliferation and modulation of cyclin-dependent kinase inhibitor p21(cip1) in vascular remodelling during vein arterialization in the rat.

Neo-intima development and atherosclerosis limit long-term vein graft use for revascularization of ischaemic tissues. Using a rat model, which is technically less challenging than smaller rodents, we provide evidence that the temporal morphological, cellular, and key molecular events during vein arterialization resemble the human vein graft adaptation. Right jugular vein was surgically connected to carotid artery and observed up to 90 days. Morphometry demonstrated gradual thickening of the medial layer and important formation of neo-intima with deposition of smooth muscle cells (SMC) in the subendothelial layer from day 7 onwards. Transmission electron microscopy showed that SMCs switch from the contractile to synthetic phenotype on day 3 and new elastic lamellae formation occurs from day 7 onwards. Apoptosis markedly increased on day 1, while alpha-actin immunostaining for SMC almost disappeared by day 3. On day 7, cell proliferation reached the highest level and cellular density gradually increased until day 90. The relative magnitude of cellular changes was higher in the intima vs. the media layer (100 vs. 2 times respectively). Cyclin-dependent kinase inhibitors (CDKIs) p27(Kip1) and p16(INKA) remained unchanged, whereas p21(Cip1) was gradually downregulated, reaching the lowest levels by day 7 until day 90. Taken together, these data indicate for the first time that p21(Cip1) is the main CDKI protein modulated during the arterialization process the rat model of vein arterialization that may be useful to identify and validate new targets and interventions to improve the long-term patency of vein grafts.

Decellularized and photooxidatively crosslinked bovine jugular veins as potential tissue engineering scaffolds.

Decellularization means and altering crosslinking approaches were two promising alternatives for glutaraldehyde fixation to biological tissues. Bovine jugular veins (BJVs) were decellularized by a multi-step detergent-enzymatic extraction method, then photooxidatively crosslinked. Gross and histological integrity of which was retained. Ultrastructures showed integrity of collagen fibrils and elastic fibers, and a basement membrane free luminal surface. Mechanical strength test and tissue protein extraction assay demonstrated their tissue stability. After being pre-coated with gelatin, collagen IV and fibronectin, cultured human umbilical vein endothelial cells were planted in the luminal surface of decellularized plus photooxidized BJV patches for seven days. Endothelial cells were denser in pre-coated patches than in uncoated controls. A rat subcutaneous implantation model revealed more resistance against in vivo degradation for further crosslinked BJV patches than decellularized patches at 12-week retrieval. Host cells were all layer repopulated for both. Histological examination and content assay demonstrated collagen and glycosaminoglycan components synthesis for decellularized plus photooxidized BJV patches. Decellularized and photooxidatively crosslinked BJV patches possess tissue integrity, excellent in vitro and in vivo tissue stability and repopulation patterns. Thus, they have potentials as tissue engineering scaffolds in future cardiovascular surgery.

[Histomorphologic properties of bovine jugular vein conduit treated withdye-mediated photooxidation following decellularization].

OBJECTIVE: To determine the histocompatibility and histoconstancy of bovine jugular vein conduit (BJVC) treated by dye-mediated photooxidation following decellularization before and after implantation in Wistar rats. METHODS: Each of 20 fresh bovine jugular veins with a retained native valve procured from a slaughterhouse was cut into 4 trial patches with valves, which were randomly divided into 4 groups. The 4 groups were treated respectively by dye-mediated photooxidation(DMP), glutaraldehyde(GA), decellularization(DC), and dye-mediated photooxidation following decellularization (DC+DMP). One of the trial patches in each group was implanted subcutaneously in the same Wistar rat. Two months later, all trial rats were killed and the specimens were retrieved. Tissue protein extraction was used to estimate the cross-linked degree of BJVC treated by dye-mediated photooxidation following decellularization. To observe the morphologic properties of the specimens, HE staining and electron microscopes were used. RESULTS: Compared with others, the patches in the DC+DMP group were flexible, stretched, and relatively intact; lining endothelium was comparatively smooth; collagen fiber structure was slightly loose intact; and many cells were uniformly infiltrated in all layers. CONCLUSION: BJVC treated by dye-mediated photooxidation following decellularization is superior to others in histocompatibility, and the rate of degradation can be regulated by the degree of dye-mediated photooxidation.

Transient elastic support for vein grafts using a constricting microfibrillar polymer wrap.

Arterial vein grafts (AVGs) often fail due to intimal hyperplasia, thrombosis, or accelerated atherosclerosis. Various approaches have been proposed to address AVG failure, including delivery of temporary mechanical support, many of which could be facilitated by perivascular placement of a biodegradable polymer wrap. The purpose of this work was to demonstrate that a polymer wrap can be applied to vein segments without compromising viability/function, and to demonstrate one potential application, i.e., gradually imposing the mid-wall circumferential wall stress (CWS) in wrapped veins exposed to arterial levels of pressure. Poly(ester urethane)urea, collagen, and elastin were combined in solution, and then electrospun onto freshly-excised porcine internal jugular vein segments. Tissue viability was assessed via Live/Dead staining for necrosis, and vasomotor challenge with epinephrine and sodium nitroprusside for functionality. Wrapped vein segments were also perfused for 24h within an ex vivo vascular perfusion system under arterial conditions (pressure = 120/80 mmHg; flow = 100 mL/min), and CWS was calculated every hour. Our results showed that the electrospinning process had no deleterious effects on tissue viability, and that the mid-wall CWS vs. time profile could be dictated through the composition and degradation of the electrospun wrap. This may have important clinical applications by enabling the engineering of an improved AVG.

[Comparison between effects of small intestinal submucosa graft and inside-out vein graft on repairing peripheral nerve defects].

OBJECTIVE: To make a comparison between the effects of the small intestinal submucosa (SIS) graft and the inside-out vein graft on repairing the peripheral nerve defects. METHODS: SIS was harvested from the fresh jejunum of the quarantined pig by curetting the musoca, the tunica serosa, and the myometrium; then, SIS was sterilized, dried and frozen before use. Thirty-six male SD rats were divided into 3 groups randomly, with 12 rats in each group. Firstly, the 10-mm defects in the right sciatic nerves were made in the rats and were respectively repaired with the SIS graft (Group A), the inside-out autologous vein graft (Group B), and the auto-nerve graft (Group C). At 6 weeks and 12 weeks after the operations, the right sciatic nerves were taken out, and the comparative evaluation was made on the repairing effects by the histological examination, the neural electrophysiological examination, the computerized imaging analysis, and the Trueblue retrograde fluorescence trace. RESULTS: The histological examination showed that the regenerated nerve fibers were seen across the defects in the three groups at 6 weeks after the operations. The nerve fibers were denser, the formed nerve myelin was more regular, and the fibrous tissue was less in Group A than in Group B; the nerve regeneration was more similar between Group A and Group C. At 12 weeks after the operations, the neural electrophysiological examination showed that the neural conductive rate was significantly lower in Group B than in Groups A and C (P<0.05), but no statistically significant difference was found between Group A and Group C (P > 0.05); the component potential wave amplitude was not statistically different between Group A and Group B; however, the amplitude was significantly lower in Groups A and B than in Group C (P < 0.05). At 6 weeks and 12 weeks after the operations, the computerized imaging analyses showed that the axis-cylinder quantity per area and the nerve-tissue percentage were significantly greater in Group A than in Group B (P < 0.05); the average diameter of the regenerated axis cylinder, the axis-cylinder quantity per area, and the nerve-tissue percentage were significantly lesser in Group B than in Group C (P < 0.05). At 12 weeks after the operations, the Trueblue retrograde fluorescence trace revealed that the positively-labeled neurons were found in the lumbar 3-6 dorsal root ganglion sections in the three groups. CONCLUSION: The small intestinal submucosa graft is superior to the autologous inside-out vein graft in repairing the peripheral nerve defects and it is close to the auto-nerve graft in bridging the peripheral nerve defects. Therefore, the small intestinal submucosa is a promising biological material used to replace the auto-nerve graft.

Effect of head rotation on vascular anatomy of the neck: an ultrasound study.

Carotid artery injury is a serious complication of landmark-guided internal jugular catheterization. Studies have determined that the internal jugular vein (IJV) frequently overlaps the carotid artery (CA), which has been postulated to increase the rate of arterial injury. The purpose of this study was to define the anatomic relationship of the IJV and CA by describing CA overlap by the more superficial IJV. We also seek to determine the effect of head rotation on the amount of overlap, which may have implications for IJV catheter placement. We prospectively studied the vascular anatomy of the neck in 156 Emergency Department patients. The primary intervention was head rotation to the left, as if the patient was positioned for right IJV catheterization. The patient's head was positioned at 0, 45 and 90 degrees of rotation. Ultrasound images were obtained in a transverse orientation. The percentage overlap of the CA by the IJV was measured. We also measured the distance between the jugular vein and the carotid artery. In neutral position, there was a mean overlap of 29% at the apex of the sternocleidomastoid. As the head was turned, the percent overlap increased. At 90 degrees, there was a mean overlap of 72%. Differences were determined to be significant by analysis of variance (ANOVA) with a p < 0.001. Furthermore, we found a distance of 10 mm between IJV and CA when the head is in neutral position. As the head was turned, the jugular-carotid distance decreased to 1 mm in the far lateral head position. These differences were also found to be significant by ANOVA with a p < 0.001. We concluded that the IJV overlaps the CA in the neutral position to a significant degree. This overlap increases until the head is fully turned, where most of the CA is overlapped by the IJV. This may help explain the mechanism of CA puncture. We propose two modifications to standard IJV line technique: minimize the patients' head rotation; and use ultrasound guidance for IJV catheterization.

Endovascular delivery of vein segments with valves versus direct anastomosis.

PURPOSE: To demonstrate an experimental model designed to allow placement of a vein segment containing a valve into a femoral vein without the need for anastomoses or surgical incision on the target limbs. METHODS: Segments of jugular veins containing valves were harvested bilaterally from 7 female dogs weighing 30 to 40 kg. One of the vein segments was then interposed into one femoral vein, using a standard surgical end-to-end anastomosis. Another segment was loaded into a self-expanding nitinol stent, everted, and secured outside of the stent. This vein-coated stent was then deployed from the jugular approach into the opposite common femoral vein. The endpoint of the study was thrombosis of one of the veins segments or patency at 120 days. The function of the valves was tested prior to completion of the study by instilling dye under incremental pressures and recording the pressure necessary to cause reflux. Light microscopy and electron microscopy were utilized to evaluate structure of the valves at study endpoint. RESULTS: Both grafts in one dog occluded during the second week after surgery. Anastomotic and vein-stented sites remained patent in the remaining 6 animals for 120 days. Retrograde phlebography demonstrated valve competency bilaterally in all cases. The reflux pressures on the stented side averaged 70 mmHg while the transplanted vein segment averaged 55 mmHg. Light microscopy and electron microscopy showed intact vein valve structure in all segments at the completion of the study. CONCLUSIONS: This experimental work demonstrates that endovascular delivery of a native canine vein containing a competent valve is feasible and effective.

Status of internal jugular veins in patients with carcinomas of the head and neck area.

OBJECTIVE: To assess the status of internal jugular veins (IJV) in patients with head and neck carcinomas. STUDY DESIGN AND SETTING: This study included 108 IJV of 54 cancer patients who were prospectively evaluated between September 1994 and February 1997. Patency, presence of thrombosis, characteristics of vein wall, compressibility, area of the veins both in rest and during Valsalva maneuver, expiratory flow speed, Valsalva flow speed, jugular flow in each side, and total jugular flow were registered in all cases. Also, 30 IJV of 15 normal volunteers were used as a control group. The study was performed in a tertiary care referral center. RESULTS: Right expiratory flow speed was higher in volunteers (P = 0.0280), and left basal area was bigger in oncologic patients (P = 0.0394). No significant changes were found between cancer patients and controls in the remaining parameters (P > 0.05). CONCLUSIONS AND SIGNIFICANCE: According to these results, head and neck carcinomas do not seem to affect the ultrasonographic characteristics of IJV. Thus, preoperative evaluation of IJV is not mandatory in these patients.

Bovine valved xenograft in pulmonary position: medium-term follow-up with excellent hemodynamics and freedom from calcification.

BACKGROUND: This study was designed to evaluate the outcome of Contegra xenograft valved conduit (Contegra, Medtronic Inc, Minneapolis, MN). METHODS: From April 1999 to December 2003, 67 patients with a mean age of 16.1 +/-15.0 years (2 months to 53 years) and a mean weight of 39.7 +/- 27.1 kg (4 to 95 kg) were discharged after implantation of a Contegra conduit. The diagnosis contained the following: pulmonary valve replacement during Ross operation (n = 27), pulmonary valve regurgitation (n = 9), tetralogy of Fallot (n = 7), pulmonary atresia with ventricular septal defect (n = 7), double outlet right ventricle (n = 7), truncus arteriosus (n = 5), Taussig-Bing (n = 2), obstructed conduit (n = 2), and double discordance (n = 1). Conduit size was 14 mm in 2, 16 mm in 7, 18 mm in 12, 20 mm in 13, and 22 mm in 33 patients. Mean cardiopulmonary bypass was 155 +/- 48 min (65 to 337 min) and mean aortic cross clamping was 69 +/- 38 min (0 to 146 min). All patients underwent echocardiography, 23 of 67 (34%) patients had cardiac catheterization, and 23 of 67 (34%) patients had electrocardiograph-gated multislice computer tomography. RESULTS: In a mean follow-up of 26.4 months (1 to 56 months) there was one late death (1 of 67 patients; 1.5% mortality) unrelated to the conduit. Five patients underwent reoperation; four were nonconduit-related and one was to replace a twisted conduit. Five patients underwent interventional cardiology; three were nonconduit-related and two were to stent a twisted or stenotic conduit. Echocardiography showed absent valve regurgitation in 30 of 67 (45%) patients, trivial in 21 of 67 (31%) patients, mild in 16 of 67 (24%) patients. The transconduit pressure gradient remained stable during follow-up, with peak pressure gradient 17 +/- 11 mm Hg and mean gradient 8 +/- 6 mm Hg. Internal diameters corresponded to 110% +/- 20% of the implanted diameter at level of proximal anastomosis, 112% +/- 18% at valve level, and 110% +/- 14% at distal anastomosis. Calcifications were not found, with the exception of a minimal (2.3 mm) parietal calcification. CONCLUSIONS: The Contegra valved conduit provided excellent morphology and hemodynamics, and freedom from calcification in a medium-term follow-up.

A long term comparison between Denacol EX-313-treated bovine jugular vein graft and ultrafine polyester fiber graft for reconstruction of tight ventricular outflow tract in dogs.

A Denacol EX-313 (Denacol)-treated bovine venous graft and an ultrafine polyester fiber (UFPF) graft were transplanted as patch graft into the right ventricular outflow tract under extracorporeal circulation in six dogs each experimentally. Hemodynamics in right heart and histological findings around the graft were compared between both groups over a period of one year after grafting. Pressure measurements and angiocardiography were performed through a cardiac catheter. Right ventricular pressure, pulmonary artery pessure, and right ventricle to pulmonary artery gradient were within normal limits in both groups at 1, 2, 3, 4, 6, and 12 months or more after grafting. No difference were seen between the values for the Denacol and the UFPF group. Histologically, the medial surface at the site of grafting was covered with vascular endothelial cells at one month after grafting in both groups. The density of the vascular endothelial cells increased with time after grafting, showing no clear difference between the two groups. Subendothelial layers comprised of collagen fibers, elastic fibers, and inflammatory cells decreased with time in both groups, but there was less cell infiltration in the Denacol group than in the UFPF group at all time points after grafting. In addition, the central cut thickness value of the graft tended to be thinner in the Denacol group than in the UFPF group at all observation time points after grafting. In the Denacol group, very slight metaplasia of cartilage was noted in a portion of the graft margin at six months or more after grafting, but no other abnormalities were observed. These results suggest that the Denacol-treated bovine venous graft has better grafting characteristics than the UFPF graft with easier intra-operative handlings and less tissue reactions after grafting.

Overexpression of G protein-coupled receptor kinase-2 in smooth muscle cells reduces neointimal hyperplasia.

The activation of vascular smooth muscle cells (SMCs) in neointimal hyperplasia involves signaling through receptor tyrosine kinases as well as G protein-coupled receptors. Overexpression of G protein-coupled receptor kinase-2 (GRK2) in SMCs can attenuate mitogenic signaling and proliferation in response to not only several G protein-coupled receptor agonists, but also platelet-derived growth factor (PDGF). To test whether overexpression of GRK2 could inhibit other SMC responses implicated in neointimal hyperplasia, we assessed SMC chemotaxis and mitogenic signaling evoked by PDGF and G(q)-coupled receptor agonists. To test the effects of GRK2 overexpression on neointimal hyperplasia in vivo, we employed a rabbit autologous vein graft model system. GRK2 overexpression reduced PDGF-promoted SMC chemotaxis by 85% (P<0.01), but had no effect on chemotaxis promoted by epidermal growth factor (EGF). Congruently, GRK2 overexpression reduced by approximately 50% (P<0.05) the [(3)H]thymidine incorporation induced by combinations of PDGF and Gq-coupled receptor agonists, but had no effect on that induced by PDGF plus EGF. PDGF-, but not EGF-promoted phosphoinositide 3-kinase activity in SMCs was also inhibited by GRK2 overexpression. In rabbit vein grafts, we achieved GRK2 overexpression in medial SMCs, reduced cell proliferation during the first week after graft implantation, and reduced steady state neointimal thickness by 29% (P<0.01), without affecting medial thickness or potentiating SMC apoptosis. Because of its ability to dampen chemotactic and mitogenic signaling through PDGF and Gq-coupled receptors, GRK2 overexpression in SMCs may be a useful therapeutic approach for neointimal hyperplasia.