Ipsilateral Jugular Vein Research Articles

Abstract 466: CX3CR1 Down Regulation Reduces Venous Neointimal Hyperplasia Formation in a Murine Hemodialysis Vascular Access Model

Introduction: Venous neointimal hyperplasia (VNH) is a major cause of hemodialysis arteriovenous fistula (AVF) vascular access failure. CX3CR1 mediates macrophage infiltration into the vasculature. Mice were used which had been genetically engineered to knock in the human CX3CR1 gene. Hypothesis: The hypothesis to be tested is that increased CX3CR1 gene expression results in VNH formation associated with AVF. Methods: We used 50 CX3CR1 knock in mice which were divided into 2 groups: 1. CX3CR1 antibody (30 mg/kg administered intraperitoneally two times per week) or vehicle (equal amount of volume used for CX3CR1 antibody administered intraperitoneally). AVFs were created by connecting the carotid artery to ipsilateral jugular vein 28 days after nephrectomy was performed to induce chronic kidney disease. Histology and Immunohistochemistry analysis at the outflow vein of AVF were performed to assess the pathological changes. Results: There was a significant decrease in neointima area in the outflow veins of AVF in CX3CR1 antibody group compared to the vehicle group at day 28 (43085 ± 12678 vs. 58963.4 ± 9273 μm 2 , P<0.05). There was a significant decrease in the ratio of neointima/media+adventitia area in the outflow veins of AVF in CX3CR1 antibody group compared to the vehicle group at day 28 (0.34 ± 0.1 vs. 0.61 ± 0.1, P<0.05). Cell density in neointima area in CX3CR1 group outflow veins was significantly lower than the vehicle group at day 14 (9600 ± 1000 vs. 13000 ± 3000 /mm 2 , P<0.01). There was a significant decrease in the average CD68-positive cell density in the CX3CR1 group outflow veins compared to the vehicle group (0.96 ± 0.34 vs.15.9 ±10, P<0.001) at day 14. Conclusion: Decreasing CX3CR1 significantly reduces macrophages infiltration and results in a significant reduction in VNH. This study provides a rationale for using CX3CR1 antibody in reducing VNH formation.

Antagonism of cannabinoid receptor 1 attenuates the anti-inflammatory effects of electroacupuncture in a rodent model of migraine.

The anti-nociceptive effects of electroacupuncture (EA) in migraine have been documented in multiple randomised controlled trials. Neurogenic inflammation plays a key role in migraine attacks, and the anti-inflammatory effects of acupuncture have been associated with the type 1 cannabinoid (CB1) receptor. To investigate whether CB1 receptors mediate the anti-inflammatory effects of EA on migraine attacks. A migraine model was produced in Sprague-Dawley rats by unilateral electrical stimulation of the trigeminal ganglion (TGES). Rats received EA daily on the 5 days preceding TGES with (TGES+EA+SR141716 group) or without (TGES+EA group) intraperitoneal injections of the CB1 receptor antagonist SR141716. Another group of TGES rats (TGES+MA group) and a non-TGES sham-operated group of rats (Sham+MA group) received minimal acupuncture (MA). Calcitonin gene-related peptide (CGRP) and prostaglandin E2 (PGE2) concentrations were determined in serum obtained from the ipsilateral jugular vein at initiation of TGES and 5 min after. Postmortem interleukin (IL)-1β and cyclooxygenase (COX)2 protein levels in the trigeminal ganglion (TG) and plasma protein extravasation (PPE) in the dura mater were assessed. TGES induced increases in serum CGRP and PGE2 levels (TGES+MA vs baseline and vs Sham: all p<0.001), as well as IL-1β and COX2 protein expression in the TG, and neurogenic PPE levels (TGES+MA vs Sham+MA: all p<0.001). EA attenuated TGES-induced increases in the levels of these proteins (TGES+EA vs TGES+MA: all p<0.001). CB1 receptor antagonism reversed the effects of EA (TGES+EA+SR141716 vs TGES+EA: all p<0.05). CB1 receptors appear to mediate anti-inflammatory effects of EA in a rat model of migraine.

Pseudo-low Frequency Hearing Loss and Its Improvement After Treatment May Be Objective Signs of Significant Vascular Pathology in Patients With Pulsatile Tinnitus.

In patients with pulsatile tinnitus (PT), physical examination such as auscultation with head position change or digital compression over the ipsilateral jugular vein provides physicians with important information. However, objective diagnosis of PT is sometimes limited because 1) audible bruit is absent on auscultation in some patients, 2) abnormal vascular structures found in radiologic evaluation is not always pathognomonic because they can be found in asymptomatic subjects as well, and 3) although an objective diagnostic tool using transcanal sound recording has recently been introduced, special equipment is needed. In this regard, recent studies that have reported ipsilateral low-frequency hearing loss (LFHL) on pure-tone audiometry (PTA) in some patients with PT, and its recovery after successful management, prompted us to conduct a retrospective observational study on the characteristics of the audiometric profile, the association between the audiometric profile and radiologic findings, and pre- and posttreatment changes in low-frequency hearing thresholds in PT patients. We tested two hypotheses: PT patients with marked vascular pathologies located close to the cochlea may show ipsilateral pseudo-LFHL (PLFHL) because of the masking effects of the PT itself, and their PLFHL may disappear if their vascular pathology is successfully managed by surgical or endovascular intervention. Retrospective case review. Tertiary referral center. A total of 85 PT subjects who underwent both audiologic and radiologic examinations. All patients' pre- and posttreatment PTA thresholds and radiologic findings were analyzed. By comparing the LFHL (an ipsilateral hearing threshold greater than 10 dB HL at both 250 and 500 Hz or greater than 20 dB HL at either 250 or 500 Hz compared with the contralateral side) group and a non-LFHL group with regard to the incidence of vascular structural abnormalities, we evaluated the incidence of abnormal vascular structures in the head and neck between the LFHL and non-LFHL groups. In addition, by comparing pre- and posttreatment PTA thresholds of seven PT patients with ipsilateral LFHL, we further evaluated the changes in low-frequency hearing thresholds and their role as an objective sign for diagnosis and outcome evaluation. Of 85 patients, 22 (25.9%) presented with ipsilateral LFHL. Compared with patients without this condition, patients with ipsilateral LFHL showed a significantly higher rate of abnormal vascular structure. In addition, most of the radiologic abnormalities found in the LFHL group were highly suspicious causative lesions that are responsible for the perception of PT according to the previous literature. In eight PT patients with ipsilateral LFHL who underwent both pre- and posttreatment audiograms, the average posttreatment pure-tone threshold at 250 Hz showed significant improvement compared with the pretreatment threshold. PT patients presenting with ipsilateral LFHL have higher possibility of having a discrete vascular pathology near the cochlea on radiologic evaluation. As ipsilateral LFHL improves in most patients after treatment, LFHL in patients with PT may be PLFHL because of the masking effects of the pulsatile sound, and the changes in the low-frequency thresholds may be applicable for objective diagnosis and evaluation of the effects of the treatment.

The Role of Repeat Administration of Adventitial Delivery of Lentivirus-shRNA-Vegf-A in Arteriovenous Fistula to Prevent Venous Stenosis Formation

PurposeTo determine if a second dose of a lentivirus mediated small hairpin RNA that inhibits Vegf-A gene expression (LV-shRNA-Vegf-A) can improve lumen vessel area (LVA) of the outflow vein of an arteriovenous fistula (AVF) and decrease venous neointimal hyperplasia. Materials and MethodsChronic kidney disease was created in C57BL/6 mice; 28 days later, an AVF was created by connecting the right carotid artery to the ipsilateral jugular vein. Immediately after AVF creation, 5 × 106 plaque-forming units of LV-shRNA-Vegf-A or control shRNA was administered to the adventitia of the outflow vein, and a second dose of the same treatment was administered 14 days later. Animals were sacrificed at 21 days, 28 days, and 42 days after AVF creation for reverse transcription polymerase chain reaction and histomorphometric analyses. ResultsBy day 21, there was a 125% increase in the average LVA (day 21, P = .11), with a decrease in cell proliferation (day 21, P = .0079; day 28, P = .28; day 42, P = .5), decrease in α-smooth muscle cell actin staining (day 21, P < .0001; day 28, P < .05; day 42, P = .59), and decrease in hypoxic stress (day 21, P < .001; day 28, P = .28; day 42, P = .46) in LV versus control shRNA vessels. ConclusionsA second dose of LV-shRNA-Vegf-A administration results in a moderate improvement in LVA at day 21.

Enhanced brain release of erythropoietin, cytokines and NO during carotid clamping

Although effective and safe, carotid endarterectomy (CEA) implies a reduced blood flow to the brain and likely an ischemia/reperfusion event. The high rate of uneventful outcomes associated with CEA suggests the activation of brain endogenous protection mechanisms aimed at limiting the possible ischemia/reperfusion damage. This study aims at assessing whether CEA triggers protective mechanisms such as brain release of erythropoietin and nitric oxide. CEA was performed in 12 patients; blood samples were withdrawn simultaneously from the surgically exposed ipsilateral jugular and leg veins before, during (2 and 40 min) and after clamp removal (2 min). Plasma antioxidant capacity, carbonylated proteins, erythropoietin, nitrates and nitrites (NOx) were determined. No changes in intraoperative EEG, peripheral and transcranial blood oxygen saturation were detectable, and no patients showed any neurologic sign after the intervention. Antioxidant capacity and protein carbonylation in plasma were unaffected. Differently, erythropoietin, VEGF, TNF-α and NOx increased during clamping in the jugular blood (2 and 40 min), while no changes were observed in the peripheral circulation. These results show that blood erythropoietin, VEGF, TNF-α, and NOx increased in the brain during uncomplicated CEA. This may represent an endogenous self-activated neuroprotective mechanism aimed at the prevention of ischemia/reperfusion damage.

Inhibition of intimal hyperplasia of the vein graft with degradable poly lactic-co-glycolic acid vascular external sheaths carrying slow-release bosentan.

Intimal hyperplasia is a major reason for the restenosis of vein grafts. A vascular external sheath was designed to inhibit intimal hyperplasia of vein grafts. Using the biodegradable material poly(lactic-co-glycolic acid) and fibrin, a high porosity external sheath carrying bosentan with a stratified internal spiral structure was made by grouping mould extraction and low-temperature deposition techniques. Bosentan, a dual endothelin A and B receptor antagonist, was carried in the new designed external sheath, and could be slowly released. Rabbits underwent carotid bypass with ipsilateral jugular vein without external sheath (control, Group C), with external sheath (Group S) or with external sheath carrying bosentan (Group S + B). Eight weeks after interposition, ultrasonography indicated that the change rate of the diameter of vein grafts of Group C (42.3 ± 5.8%) was much higher than that of Group S (18.5 ± 8.6%) or S + B (1.1 ± 13.2%) (P < 0.01, respectively). The change rate of peak velocity of Group S + B (-0.5 ± 9.8%) was lower than that of Group S (5.7 ± 7.4%) or C (25.6 ± 13.1%) (P < 0.01 vs Group C; P < 0.05 vs Group S). The sheaths degraded completely 9 weeks after interposition and the histological examination showed that the ratio of long/short diameter of vein grafts was much higher in Group C (P < 0.01, respectively). The ratio of the area of intima-media to the area of lumen and the ratio of thickness of intima to the thickness of media of Group S + B were significantly lower (P < 0.01 vs Group C; P < 0.05 vs Group S, respectively). Masson and Alcian Blue staining indicated that the remodelling of collagen and the distribution of proteoglycan in vein grafts of Group S + B were more similar to those of the artery. The degradable vascular external sheath with slow-release bosentan can inhibit hyperplasia of intima, and improve the shape of experimental vein grafts.

¹H-MRS before and after resuscitation following selective cerebral ultra-profound hypothermic blood flow occlusion in monkeys.

We investigated the effect of selective cerebral ultra-profound hypothermic blood flow occlusion on brain tissue and cell metabolism to ascertain the efficacy and safety of selective deep hypothermic technologies using proton magnetic resonance spectroscopy ((1)H-MRS). The bilateral carotid artery was blocked at room temperature for 10 min. Other neck vessels were then blocked through cold perfusion of the internal carotid artery and reflux of the ipsilateral jugular vein. Thus, selective cerebral extracorporeal circulation was established. Brain temperature was reduced to 15.1° ± 0.9°C. After 60 min, cerebral blood flow recovered naturally. Routine magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and (1)H-MRS examination of the bilateral frontal cortex and basal ganglia were performed prior to surgery and 4, 24, 72 h, 21 days after recovery. The formants and areas under the curve (AUC) of N-acetyl aspartate (NAA), choline (Cho), creatine/phosphocreatine (Cr/Cr2) were analyzed using 1H-MRS. The pre- and postoperative AUC of NAA and Cho at different time points were compared. Conventional MRI and DWI showed no abnormal signal changes in the brain parenchyma or right basal ganglia before and after surgery (P > 0.05). There was no significant difference in the ratio between NAA/(Cr+Cr2) and Cho/(Cr+Cr2) before and after surgery in the bilateral basal ganglia and frontoparietal regions of the cortex (P > 0.05). Quantitative (1)H-MRS showed that selective deep cerebral hypothermia significantly improved the brain's tolerance to ischemia and hypoxia. Our results could provide a better understanding of the efficacy and safety of selective deep hypothermia and blood flow occlusion.

Ultrasound-guided vein puncture versus surgical cut-down technique in totally implantable venous access devices (TIVADS): a prospective comparative study on safety, efficacy andcomplications.

otally implantable venous access devices (TI-VADs) consist of a central venous catheter(made of silicone rubber or polyurethane) and asubcutaneously-implanted injection port made oftitanium or plastic, providing a simple, safe, andpermanent means of accessing the vascular systemfor intravenous delivery of drugs and fluids.

Abstract 164: The Role of IEX-1 in Venous Stenosis Formation Associated With Arteriovenous Fistula Used for Hemodialysis

Purpose: The majority of patients with end stage renal disease who require hemodialysis use a arteriovenous fistula (AVF) for their vascular access. However, only 40% of AVFs are clinically usable after 1 year. Arteriovenous fistulas fail because of venous neointimal hyperplasia (VNH) that develops in the proximal outflow vein. The immediate early gene, IEX-1 (IER-3), is increased in response to shear stress and hypoxia and both factors contribute to VNH. IEX-1 expression was increased in stenotic venous stenoses removed from patients with hemodialysis vascular access compared to controls. We hypothesized that reducing the expression of IEX-1 using a knockout mouse model with chronic kidney disease (CKD) and AVFs would have decreased VNH compared to wild type (WT) mice. Methods: CKD was induced by performing a nephrectomy. Four weeks later, an AVF was placed to connect the carotid artery to ipsilateral jugular vein. The mice were sacrificed 3 and 28 days after fistula creation and outflow veins were harvested for gene expression and histomorphometric analyses. Results: By day 3, the average gene expression of vascular endothelial growth factor-A (VEGF-A) was significantly lower in the IEX-1 KO vs. WT mice (average reduction: 40%, P&lt;0.05). At day 28, the average lumen vessel area was increased significantly (average increase: 133%, P&lt;0.05, IEX-1 KO vs. WT, respectively) while the average area of the neointima was significantly decreased (average reduction: 20%, IEX-1 KO vs. WT, respectively). Accompanied with this, there was a significant decrease in α-SMA staining and Ki-67 proliferation while the average TUNEL staining was significantly increased (all P&lt;0.05, IEX-1 KO vs. WT). Finally, there was a significant decrease in the average staining intensity for VEGF-A and matrix metalloproteinase-9 (MMP-9) in the KO vs. WT mice (both, P&lt;0.05). Conclusion: A reduction in IEX-1 gene expression results in positive vascular remodeling accompanied with a reduction in proliferation and α-SMA density mediated through a VEGF-A/MMP-9 pathway. Taken collectively, these findings indicate that reducing IEX-1 expression is protective for VNH formation and provide a rationale for use of anti-IEX-1 therapies aimed at prolonging AVF function.

MRI and MR Angiography Findings to Differentiate Jugular Venous Reflux From Cavernous Dural Arteriovenous Fistula

Both jugular venous reflux (JVR) and cavernous dural arteriovenous fistula (DAVF) manifest as abnormal venous signal intensities on time-of-flight (TOF) MR angiography (MRA). We investigated brain MRI and MRA findings that might differentiate JVR from cavernous DAVF. Forty-one patients with abnormal venous signal intensities on TOF MRA in the cavernous sinus and its vicinity were selected from 1508 patients who had undergone TOF MRA over the previous 6 months. For comparison, the examinations of 26 patients with cavernous DAVF who had undergone imaging over the previous 8 years were collected. The following findings were assessed: the side and location of abnormal venous signal intensities on intracranial TOF MRA; the signal intensity of the proximal jugular vein on T2-weighted imaging; whether there was early opacification of the cavernous sinus in the arterial phase of contrast-enhanced MRA (CE-MRA); the side of jugular venous drainage in the arteriovenous phase of CE-MRA; and whether retrograde jugular venous flow was seen on neck TOF MRA. Abnormal venous signal intensities were seen on the left side in 73% of patients with JVR and 58% of patients with cavernous DAVF; involvement of the cavernous sinus was found in 12% of patients with JVR and 100% of patients with cavernous DAVF. Increased signal intensity in the ipsilateral jugular vein on T2-weighted imaging was found in 73% of JVR patients and 4% of cavernous DAVF patients. Early opacification of the cavernous sinus in the arterial phase of CE-MRA, ipsilateral jugular venous drainage in the arteriovenous phase of CE-MRA, and ipsilateral retrograde jugular venous flow on neck TOF MRA were found in 0%, 0%, and 63%, respectively, of JVR patients and in 100%, 100%, and 0%, respectively, of cavernous DAVF patients. JVR and cavernous DAVF can be differentiated from one another using MRI and MRA.

English

Central venous catheterization (CVC) via infraclavicular subclavian approach in neurosurgical patients is very common practice. Malpositioning of central venous catheter inserted into subclavian vein is a known and dreaded complication. Malpositioning of catheter tip into ipsilateral jugular vein is an unusual occurrence. We hereby describe a case where a subclavian

Gracilis Muscle‐Only Flap for Soft‐Tissue Coverage following Oncologic Surgery of the Neck

Objectives: 1) Describe the use of the gracilis muscle-only flap for the protection of neurovascular structures in the neck. 2) Recognize situations where minimizing donor-site morbidity and optimizing the aesthetic outcome preclude the use of the pectoralis or latissimus flaps. Methods: A review of records, imaging, and photographs was performed along with a review of the literature. Previous cases where the gracilis muscle was used for free tissue transfer were reviewed. Results: A 13-year-old female was referred for management of a right-sided residual malignant peripheral nerve sheath tumor. The tumor was ipsilateral to her dominant hand, and the patient was an avid volleyball player and violinist. Imaging demonstrated the tumor diffusely infiltrating structures of the carotid sheath, sternocleidomastoid muscle (SCM), and levels II - IV in the neck. The patient underwent surgical resection of the tumor and the ipsilateral SCM, carotid artery, jugular vein, vagus nerve, hypoglossal nerve, and cervical sympathetic chain. The carotid artery, vagus, and hypoglossal nerves were reconstructed with grafts. Post-operative radiation was planned, necessitating protection of the underlying grafts. A portion of the right gracilis muscle was harvested and sutured to the mastoid tip and clavicle. Vascular anastomoses were performed to nearby vessels. The patient experienced no flap donor or recipient site complications. Symmetry was excellent post-operatively. Conclusions: This novel use of the gracilis muscle for soft tissue coverage following an ablative procedure in the neck resulted in negligible donor site morbidity and an excellent aesthetic outcome in both the neck and the inner thigh.

Simvastatin reduces venous stenosis formation in a murine hemodialysis vascular access model

Venous neointimal hyperplasia (VNH) is responsible for hemodialysis vascular access malfunction. Here we tested whether VNH formation occurs, in part, due to vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase (MMP)-9 gene expression causing adventitial fibroblast transdifferentiation to myofibroblasts (α-SMA-positive cells). These cells have increased proliferative and migratory capacity leading to VNH formation. Simvastatin was used to decrease VEGF-A and MMP-9 gene expression in our murine arteriovenous fistula model created by connecting the right carotid artery to the ipsilateral jugular vein. Compared to fistulae of vehicle-treated mice, the fistulae of simvastatin-treated mice had the expected decrease in VEGF-A and MMP-9 but also showed a significant reduction in MMP-2 expression with a significant decrease in VNH and a significant increase in the mean lumen vessel area. There was an increase in terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and decreases in α-SMA density, cell proliferation, and HIF-1α and hypoxyprobe staining. This latter result prompted us to determine the effect of simvastatin on fibroblasts subjected to hypoxia in vitro. Simvastatin-treated fibroblasts had a significant decrease in myofibroblast production along with decreased cellular proliferation, migration, and MMP-9 activity but increased caspase 3 activity suggesting increased apoptosis. Thus, simvastatin results in a significant reduction in VNH, with increase in mean lumen vessel area by decreasing VEGF-A/MMP-9 pathway activity.

Facial Palsy and Nystagmus after Transvenous Embolization of a Carotid Cavernous Fistula

Facial Palsy and Nystagmus after Transvenous Embolization of a Carotid Cavernous Fistula

In vivo evaluation of the delivery and efficacy of a sirolimus-laden polymer gel for inhibition of hyperplasia in a porcine model of arteriovenous hemodialysis graft stenosis

Synthetic arteriovenous (AV) hemodialysis grafts are plagued by hyperplasia resulting in occlusion and graft failure yet there are no clinically available preventative treatments. Here the delivery and degradation of a sirolimus-laden polymer gel were monitored in vivo by magnetic resonance imaging (MRI) and its efficacy for inhibiting hyperplasia was evaluated in a porcine model of AV graft stenosis.Synthetic grafts were placed between the carotid artery and ipsilateral jugular vein of swine. A biodegradable polymer gel loaded with sirolimus (2.5mg/mL) was immediately applied perivascularly to the venous anastomosis, and reapplied by ultrasound-guided injections at one, two and three weeks. Control grafts received neither sirolimus nor polymer. The lumen cross-sectional area at the graft–vein anastomosis was assessed in vivo by non-invasive MRI. The explanted tissues also underwent histological analysis.A specifically developed MRI pulse sequence provided a high contrast-to-noise ratio (CNR) between the polymer and surrounding tissue that allowed confirmation of gel location after injection. Polymer signal decreased up to 80% at three to four weeks after injection, slightly faster than its degradation kinetics in vitro. The MR image of the polymer was confirmed by visual assessment at necropsy. On histological assessment, the mean hyperplasia surface area of the treated graft was 52% lower than that of the control grafts (0.43mm2 vs. 0.89mm2; p<0.003), while the minimum cross-sectional lumen area, as measured on MRI, was doubled (5.3mm2 vs 2.5mm2; p<0.05).In conclusion, customized MRI allowed non-invasive monitoring of the location and degradation of drug delivery polymer gels in vivo. Perivascular application of sirolimus-laden polymer yielded a significant decrease in hyperplasia development and an increase in lumen area at the venous anastomosis of AV grafts.

Abstract No. 94: Bone marrow derived cells do not contribute to venous neointimal hyperplasia (VNH) in a murine model of arteriovenous fistula with chronic kidney disease

In arterial stenosis, bone marrow derived cells have been shown to contribute to stenosis formation. We hypothesized that bone marrow derived cells may contribute to the formation of VNH in a murine model of arteriovenous fistula with chronic kidney disease. Donor mice (sm22-GFP C57BL/6) mice were killed, and their femurs and tibias removed aseptically. Marrow cavities were flushed, and single-cell suspensions prepared. Cells were washed 2 times in HBSS and resuspended at 3x107 cells/ml before transplantation. Six- to 8-week-old C57BL/6 mice received a lethal dose of whole-body irradiation at 8.5-9.0 Gray units of gamma irradiation exposure for 14.2 minutes. Irradiated recipients received 1X 107 bone marrow cells in 0.3 ml into the femoral vein within 24 hours of irradiation. Four weeks after bone marrow transplantation, a right nephrectomy was performed and the upper pole of the left kidney ligated. Four weeks later, a AVF was created from the left carotid artery to the ipsilateral jugular vein. Animals were sacrificed at day 3, 7, and 14 after fistula creation and the outflow vein embedded in paraffin for histochemical analysis. 16 mice were used and 4 died after radiation and 4 mice had thickened carotid arteries which excluded them from placement of the AVF. Therefore 8 animals were sacrificed at D3 (n=3), D7 (n=3), and D14 (n=2). Confocal microcopy for GFP was performed on paraffin embedded sections. No eGFP positive cells were identified at the venous stenosis. No eGFP bone marrow derived cells contributed to VNH formation in a murine model of AVF failure.

Time course of flow-induced adaptation of carotid artery biomechanical properties, structure and zero-stress state in the arteriovenous shunt

Numerous studies have provided evidence of diameter adaptation secondary to flow-overload, but with ambiguous findings vis à vis other morphological parameters and information on the biomechanical aspects of arterial adaptation is rather incomplete. We examined the time course of large-artery biomechanical adaptation elicited by long-term flow-overload in a porcine shunt model between the carotid artery and ipsilateral jugular vein. Post-shunting, the proximal artery flow was doubled and retained so until euthanasia (up to three months post-operatively), without pressure change. This hemodynamic stimulus induced lumen diameter enlargement, accommodated by elastin fragmentation and connective tissue accumulation, as witnessed by optical and confocal microscopy. Heterogeneous mass growth of the adventitia was observed at the expense of the media, associated with declining residual strains and opening angle at three months. The in vitro elastic properties of shunted arteries determined by inflation/extension testing were also modified, with the thickness-pressure curves shifted to larger thicknesses and the diameter-pressure curves shifted to larger diameters at physiologic pressures, resulting in normalization of intramural and shear stresses within fifteen and thirty days, respectively. We infer that the biomechanical adaptation in moderate flow-overload leads to normalization of intimal shear, without, however, restoring compliance and distensibility at mean in vivo pressure to control levels.

Inhibitory effect of polydioxanone suture external stent on the vein graft neointima thickening and the possible mechanism

Objective To evaluate the effect of a biodegradable external stent on intimal vein graft thickening in an arteriovenous bypass grafting model, and study its possible mechanism. Methods Twenty-four rabbits underwent carotid interposition bypass via ipsilateral jugular vein. Half received the polydioxanone stent ( PDS group) and half a simple vein graft (controls). Group subsets received external stent removal or sham-control exploration at 4th and 12th week. Each of the specimens was detected for pathological and molecular biological examination. Results At 4th and 12th week the PDS group had significantly less medial and intimal thickening than the control group ( P ＜ 0, 05 ), and there were fewer proliferating smooth muscle cells and extra cellular matrix formation than the control group at every interval. The proliferating cell nuclear antigen (PCNA) and angiotensin Ⅱ type 1 receptor (AT1R) were over-expressed in the tunica media and intima in control group. The transforming growth factor-β1 (TGF-β1) was expressed mostly in adventitia in PDS group. Conclusion An macro-porous nonrestrictive, PDS external stent can effectively inhibit the intimal hyperplasia in vein bypass grafts, which might be contributed to the re-distribution of TGF-β1 and AT1R. Key words: Vein graft; Intimal thickening; TGF-β1 ; AT1R

Pioglitazone prevents intimal hyperplasia in experimental rabbit vein grafts

Intimal hyperplasia is a major obstacle to patency after vein grafting. Several clinical trials revealed that pioglitazone, a peroxisome proliferator-activated receptor-γ ligand, exerts beneficial actions on cardiovascular complications. We investigated whether pioglitazone modulates intimal hyperplasia in experimental rabbit autologous vein grafts. Male Japanese White rabbits were randomly divided into two groups: one group received pioglitazone as food admixture at a concentration of 0.01%, and the other did not (control). One week later, each group underwent reversed autologous vein bypass grafting of the right common carotid artery using ipsilateral external jugular vein. Pioglitazone therapy was continued after surgery and until harvest. Intimal hyperplasia of the grafted vein was assessed at 28 days. Two weeks after implantation, proliferative cells in the neointima were identified by immunohistochemical staining with Ki-67 monoclonal antibody. To determine apoptotic cells, we performed terminal deoxynucleotidyl transferase-mediated deoxyuride-5'-triphosphate nick-end labeling (TUNEL) staining. Blood samples were collected at 28 days after implantation for measuring metabolic parameters such as plasma glucose and total cholesterol. Adiponectin levels were determined by Western blot analysis. Finally, we assessed adiponectin-related signaling pathway, 5' adenosine monophosphate-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK) in the grafted vein by Western blot analysis. Treatment with pioglitazone markedly inhibited intimal hyperplasia of carotid interposition-reversed jugular vein grafts in the pioglitazone group (0.54 ± 0.04 mm(2)) vs control (0.93 ± 0.04 mm(2); n = 7; P < .01). Pioglitazone treatment reduced the number of Ki-67-positive proliferating cells in the neointima of the vein grafts at 14 days after implantation in the pioglitazone group (4.1% ± 1.1%) vs the controls (16.8% ± 1.7%; P < .05). The frequency of TUNEL-positive apoptotic cells was enhanced by pioglitazone (3.5% ± 0.5%) vs the controls (1.2% ± 0.1%; P < .05). Pioglitazone treatment also increased plasma levels of adiponectin, a vascular protective hormone, and led to an increase in phosphorylation of AMPK and a decrease in phosphorylation of ERK in the grafted vein. Pioglitazone attenuates intimal hyperplasia of the vein graft after autologous bypass grafting by its ability to suppress cell proliferation and enhance apoptosis. Pioglitazone could represent a therapeutic target for the prevention of graft failure after bypass grafting.

Effect of eyelid manipulation and manual jugular compression on intraocular pressure measurement in dogs

To determine the effect of eyelid manipulation and manual jugular compression on intraocular pressure (IOP) measurement in clinically normal dogs. Randomized clinical trial. 30 dogs (57 eyes) without diseases or medications that affect IOP. An applanation tonometer was used to measure IOP during eyelid manipulation or jugular compression. Six manipulations were used in each eye, including minimal eyelid manipulation, maximal dorsoventral extension of the eyelids, lateral eyelid extension, manual compression of the ipsilateral jugular vein, manual compression of both jugular veins, and lateral eyelid extension with manual compression of both jugular veins. Skull type and position of globe in the orbit were recorded. The 2 manipulations that caused the greatest significant increase in mean IOP were lateral eyelid extension with compression of both jugular veins (difference from baseline IOP, 17.6 mm Hg; 95% confidence interval [CI], 15.7 to 19.5 mm Hg) and lateral eyelid extension alone (16.5 mm Hg; 95% CI, 14.6 to 18.4 mm Hg). Dorsoventral eyelid extension (6.42 mm Hg; 95% CI, 4.5 to 8.3 mm Hg) and compression of both jugular veins alone (3.0 mm Hg; 95% CI, 1.1 to 5.0 mm Hg) significantly increased mean IOP, compared with baseline. Compression of the ipsilateral jugular vein increased mean IOP (0.3 mm Hg; 95% CI, -1.6 to 2.2 mm Hg) from baseline, but not significantly. Traction on the eyelids or pressure on both jugular veins can significantly increase IOP values as measured by use of applanation tonometry in clinically normal dogs.