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The interfacility transfer (IT) of patients with a ruptured abdominal aortic aneurysm (rAAA) occurs not infrequently to allow for a higher level of care. In the present study, we evaluated, using a contemporary administrative database, the effects of IT on mortality after rAAA repair.The Healthcare Cost and Utilization Project Database for New York (2016) and New Jersey, Maryland, and Florida (2016-2017) was queried using the International Classification of Diseases, 10th edition, to identify patients who had undergone open or endovascular repair of AAAs. The hospitals were categorized into quartiles (Qs) per overall volume. The mortality rates for IT vs nontransferred (NT) rAAA patients stratified by treatment modality (open aneurysm repair of an rAAA [rOAR] vs endovascular aneurysm repair of an rAAA [rEVAR]) were compared. A Cox proportional hazard model was used to estimate the hazard ratios (HRs) for mortality.A total of 1476 patients had presented with a rAAA, of whom 673 (45.7%) were not treated. Of the remaining 803 patients, 226 (28.1%) were transferred, of whom 50 (22.1%) had died without repair after IT. The remaining 753 patients (IT, n = 176; NT, n = 576) had undergone rEVAR (n = 492) or rOAR (n = 261). The baseline characteristics were similar between the IT and NT patients, except for a greater proportion of black patients (P = .03), lower income families (P = .049), and rOAR (45.5% vs 31.4%; P = .001) for the IT patients. The overall mortality rates were similar between the NT (30.2%) and IT (27.3%) groups (P = .46). The subgroup analysis revealed that the operative mortality rates after rEVAR were similar between the NT and IT patients, without significant differences among the hospital quartiles. After rOAR, however, the operative mortality rates were lower for the IT patients, largely owing to improved outcomes in the Q4 hospitals (Q4 vs Q1-Q3, P = .001). Cox regression analysis demonstrated that age (HR, 1.03; 95% confidence interval, 1.00-1.06; P = .02) and treatment at a low-volume hospital (Q1-Q3; HR, 1.89; 95% confidence interval, 1.02-3.51; P = .04) were predictors of mortality. The total charges were similar (IT, $286,727; vs NT, $265,717; P = .38).The results from the present study have shown that 30% of rAAA patients deemed a candidate for repair will be transferred. We found that IT did not affect the mortality rates after rEVAR, irrespective of the hospital volume. For rOAR candidates, however, regionalization of care with prompt transfer to a high-volume center could improve the survival benefits without increased healthcare costs.

Background Vascular abnormalities, including dissections and aneurysms, can be found in patients with autosomal dominant kidney disease (ADPKD). While intracranial aneurysms have been reported in 10%–25% of ADPCKD, occurrences at other locations are exceedingly rare. Method This is a first case report of a patient with ADPCKD who presented with a rupture of the left external carotid artery pseudoaneurysm. Conclusion Rupture of a carotid artery aneurysm is rare with potentially high morbidity. An endovascular and surgical approach are effective strategies for successful management that depends on etiology, location, and surgeon experience.

This report presents an unusual case of traumatic iliofemoral vessel transection in a 3-year-old patient successfully reconstructed using a cryopreserved greater saphenous conduit. Five years after injury, the patient continues to do well with normal ambulation. An arterial duplex demonstrated graft patency free of aneurysmal dilatation. These encouraging results suggest that the natural history of cryopreserved conduits may differ in the pediatric population and cryopreserved conduits could be used for complex vascular reconstructions.

To determine the impact of progressive elevations in peripheral vascular disease (PVD) risk on microvascular function, we utilized eight rat models spanning “healthy” to “high PVD risk” and used a multiscale approach to interrogate microvascular function and outcomes: healthy: Sprague-Dawley rats (SDR) and lean Zucker rats (LZR); mild risk: SDR on high-salt diet (HSD) and SDR on high-fructose diet (HFD); moderate risk: reduced renal mass-hypertensive rats (RRM) and spontaneously hypertensive rats (SHR); high risk: obese Zucker rats (OZR) and Dahl salt-sensitive rats (DSS). Vascular reactivity and biochemical analyses demonstrated that even mild elevations in PVD risk severely attenuated nitric oxide (NO) bioavailability and caused progressive shifts in arachidonic acid metabolism, increasing thromboxane A2levels. With the introduction of hypertension, arteriolar myogenic activation and adrenergic constriction were increased. However, while functional hyperemia and fatigue resistance of in situ skeletal muscle were not impacted with mild or moderate PVD risk, blood oxygen handling suggested an increasingly heterogeneous perfusion within resting and contracting skeletal muscle. Analysis of in situ networks demonstrated an increasingly stable and heterogeneous distribution of perfusion at arteriolar bifurcations with elevated PVD risk, a phenomenon that was manifested first in the distal microcirculation and evolved proximally with increasing risk. The increased perfusion distribution heterogeneity and loss of flexibility throughout the microvascular network, the result of the combined effects on NO bioavailability, arachidonic acid metabolism, myogenic activation, and adrenergic constriction, may represent the most accurate predictor of the skeletal muscle microvasculopathy and poor health outcomes associated with chronic elevations in PVD risk.

Chronic, unresolved stress is a major risk factor for the development of clinical depression. While many preclinical models of stress-induced depression have been reported, the unpredictable chronic mild stress (UCMS) protocol is an established translationally-relevant model for inducing behavioral symptoms commonly associated with clinical depression, such as anhedonia, altered grooming behavior, and learned helplessness in rodents. The UCMS protocol also induces physiological (e.g., hypercortisolemia, hypertension) and neurological (e.g., anhedonia, learned helplessness) changes that are clinically associated with depression. Importantly, UCMS-induced depressive symptoms can be ameliorated through chronic, but not acute, treatment with common SSRIs. As such, the UCMS protocol offers many advantages over acute stress protocols or protocols that utilize more extreme stressors. Our protocol involves randomized, daily exposures to 7 distinct stressors: damp bedding, removal of bedding, cage tilt, alteration of light/dark cycles, social stresses, shallow water bath, and predator sounds/smells. By subjecting rodents 3-4 hr daily to these mild stressors for 8 weeks, we demonstrate both significant behavioral changes and poor health outcomes to the cardiovascular system. This approach allows for in-depth interrogation of the neurological, behavioral, and physiological alterations associated with chronic stress-induced depression, as well as for testing of new potential therapeutic agents or intervention strategies.

International audience; Major depression is an independent risk factor for the development of cardiovascular disease. This impact of depression on vascular function seems to be mediated by the endothelial dysfunction, defined as an impairment of endothelium-dependent vasorelaxation, which represents a reliable predictor of atherosclerosis and has been regularly found to be associated with depression. This study aimed at investigating aortic vascular reactivity in mice submitted to the unpredictable chronic mild stress (UCMS) procedure, a reliable model of depression. The results confirm the effectiveness of the UCMS procedure to induce neuroendocrine, physical and behavioral depression-like alterations as well as a significant decrease of acetylcholine-induced vasorelaxation without any effect on phenylephrine-induced vasoconstriction. In this study, we reveal an altered vascular reactivity in an animal model of depression, demonstrating an endothelial dysfunction reminiscent to the one found in depressed patients.

Importance Airway transplantation could be an option for patients with proximal lung tumor or with end-stage tracheobronchial disease. New methods for airway transplantation remain highly controversial. Objective To establish the feasibility of airway bioengineering using a technique based on the implantation of stented aortic matrices. Design, Setting, and Participants Uncontrolled single-center cohort study including 20 patients with end-stage tracheal lesions or with proximal lung tumors requiring a pneumonectomy. The study was conducted in Paris, France, from October 2009 through February 2017; final follow-up for all patients occurred on November 2, 2017. Exposures Radical resection of the lesions was performed using standard surgical techniques. After resection, airway reconstruction was performed using a human cryopreserved (−80°C) aortic allograft, which was not matched by the ABO and leukocyte antigen systems. To prevent airway collapse, a custom-made stent was inserted into the allograft. In patients with proximal lung tumors, the lung-sparing intervention of bronchial transplantation was used. Main Outcomes and Measures The primary outcome was 90-day mortality. The secondary outcome was 90-day morbidity. Results Twenty patients were included in the study (mean age, 54.9 years; age range, 24-79 years; 13 men [65%]). Thirteen patients underwent tracheal (n = 5), bronchial (n = 7), or carinal (n = 1) transplantation. Airway transplantation was not performed in 7 patients for the following reasons: medical contraindication (n = 1), unavoidable pneumonectomy (n = 1), exploratory thoracotomy only (n = 2), and a lobectomy or bilobectomy was possible (n = 3). Among the 20 patients initially included, the overall 90-day mortality rate was 5% (1 patient underwent a carinal transplantation and died). No mortality at 90 days was observed among patients who underwent tracheal or bronchial reconstruction. Among the 13 patients who underwent airway transplantation, major 90-day morbidity events occurred in 4 (30.8%) and included laryngeal edema, acute lung edema, acute respiratory distress syndrome, and atrial fibrillation. There was no adverse event directly related to the surgical technique. Stent removal was performed at a postoperative mean of 18.2 months. At a median follow-up of 3 years 11 months, 10 of the 13 patients (76.9%) were alive. Of these 10 patients, 8 (80%) breathed normally through newly formed airways after stent removal. Regeneration of epithelium and de novo generation of cartilage were observed within aortic matrices from recipient cells. Conclusions and Relevance In this uncontrolled study, airway bioengineering using stented aortic matrices demonstrated feasibility for complex tracheal and bronchial reconstruction. Further research is needed to assess efficacy and safety. Trial Registration clinicaltrials.gov Identifier:NCT01331863

We describe the inadvertent cannulation of the proximal descending thoracic aortic stent with a five French sheath during attempted pacemaker placement in an 88- year-old male. The injury was managed successfully by the percutaneous placement of a thoracic aortic stent graft with good outcome. Our case highlights the feasibility of managing this uncommon injury with this technique.

The metabolic syndrome (MetS) is highly prevalent in the North American population and is associated with increased risk for development of cerebrovascular disease. This study determined the structural and functional changes in the middle cerebral arteries (MCA) during the progression of MetS and the effects of chronic pharmacological interventions on mitigating vascular alterations in obese Zucker rats (OZR), a translationally relevant model of MetS. The reactivity and wall mechanics of ex vivo pressurized MCA from lean Zucker rats (LZR) and OZR were determined at 7–8, 12–13, and 16–17 wk of age under control conditions and following chronic treatment with pharmacological agents targeting specific systemic pathologies. With increasing age, control OZR demonstrated reduced nitric oxide bioavailability, impaired dilator (acetylcholine) reactivity, elevated myogenic properties, structural narrowing, and wall stiffening compared with LZR. Antihypertensive therapy (e.g., captopril or hydralazine) starting at 7–8 wk of age blunted the progression of arterial stiffening compared with OZR controls, while treatments that reduced inflammation and oxidative stress (e.g., atorvastatin, rosiglitazone, and captopril) improved NO bioavailability and vascular reactivity compared with OZR controls and had mixed effects on structural remodeling. These data identify specific functional and structural cerebral adaptations that limit cerebrovascular blood flow in MetS patients, contributing to increased risk of cognitive decline, cerebral hypoperfusion, and ischemic stroke; however, these pathological adaptations could potentially be blunted if treated early in the progression of MetS.

Objective Chronic presentation of the MS is associated with an increased likelihood for stroke and poor stroke outcomes following occlusive cerebrovascular events. However, the physiological mechanisms contributing to compromised outcomes remain unclear, and the degree of cerebral cortical MVD may represent a central determinant of stroke outcomes. Methods This study used the OZR model of MS and clinically relevant, chronic interventions to determine the impact on cerebral cortical microvascular rarefaction via immunohistochemistry with a parallel determination of cerebrovascular function to identify putative mechanistic contributors. Results OZR exhibited a progressive rarefaction (to ~80% control MVD) of the cortical microvascular networks vs. lean Zucker rats. Chronic treatment with antihypertensive agents (captopril/hydralazine) had limited effectiveness in blunting rarefaction, although treatments improving glycemic control (metformin/rosiglitazone) were superior, maintaining ~94% control MVD. Chronic treatment with the antioxidant TEMPOL severely blunted rarefaction in OZR, although this ameliorative effect was prevented by concurrent NOS inhibition. Conclusions Further analyses revealed that the maintenance of glycemic control and vascular NO bioavailability were stronger predictors of cerebral cortical MVD in OZR than was prevention of hypertension, and this may have implications for chronic treatment of CVD risk under stroke-prone conditions.

Background Rates of major venous injury are now being reported at between 1% and 15%. Risk factors for injury include the previous spine surgery, level of exposure, and number of retractors used. To review and describe the evolution of our use of stent grafts for repair of life-threatening ilio-caval injuries encountered during anterior exposure lumbosacral (L-S) spine surgery from rescue utilization after failed direct repair to preferred modality using occlusion balloons and covered stents akin to the modern management of the ruptured abdominal aortic aneurysm (AAA) with endovascular aneurysm repair. Methods Five-year retrospective review of all anterior and retroperitoneal spine procedures was performed at our institution. Results One hundred two procedures were done. Major ilio-caval injury occurred in 3/102 (2.9%) cases. Average blood loss per case decreased as our approach evolved from unsuccessful direct open repair with percutaneous endovascular rescue to primary percutaneous endovascular repair. All treated patients had patent venous repair in short-term follow-up with computed tomography angiography. Conclusions Identification and rapid direct repair of major ilio-caval injuries during anterior approach spine surgery can be extremely challenging. When control of these potentially fatal injuries is required, our choice is primary endovascular repair using the modern techniques for endovascular management of ruptured AAA with endovascular aneurysm repair.

The presence of chronic, unresolvable stresses leads to negative health outcomes, including development of clinical depression/depressive disorders, with outcome severity being correlated with depressive symptom severity. One of the major outcomes associated with chronic stress and depression is the development of cardiovascular disease (CVD) and an elevated CVD risk profile. However, in epidemiological research, sex disparities are evident, with premenopausal women suffering from depressive symptoms more acutely than men, but also demonstrating a relative protection from the onset of CVD. Given this, we investigated the differential effect of sex on conduit artery and resistance arteriolar function in male and female mice following 8 wk of an unpredictable chronic mild stress (UCMS) protocol. In males, plasma cortisol and depressive symptom severity (e.g., coat status, anhedonia, delayed grooming) were elevated by UCMS. Endothelium-dependent dilation to methacholine/acetylcholine was impaired in conduit arteries and skeletal muscle arterioles, suggesting a severe loss of nitric oxide bioavailability and increased production of thromboxane A2 vs. prostaglandin I2 associated with elevated reactive oxygen species (ROS) and an increased level of systemic inflammation. Endothelium-independent dilation was intact. In females, depressive symptoms and plasma cortisol increases were more severe than in males, although alterations to vascular reactivity were blunted, including the effects of elevated ROS and inflammation on dilator responses. These results suggest that compared with males, female rats are more susceptible to chronic stress in terms of the severity of depressive behaviors, but that the subsequent development of vasculopathy is blunted owing to an improved ability to tolerate elevated ROS and systemic inflammatory stress.

Chronic stress/depressive symptoms impair the normal patterns of vascular reactivity. However, they also can increase CVD risk owing to an elevation in markers of the metabolic syndrome (e.g., blood pressure, glycemic control, dyslipidemia). To interrogate this, we imposed 8 weeks of unpredictable chronic mild stress (UCMS) onto lean (LZR) and obese (OZR) Zucker rats to determine their behavioral and vascular outcomes. UMCS resulted in depressive symptoms in LZR, including reduced chronic and stimulated grooming, learned helplessness, and increased plasma cortisol. A directionally consistent, although milder, effect was determined in control OZR. In ex vivo aortic rings and skeletal muscle arterioles, endothelium-dependent dilation was blunted by either metabolic syndrome (OZR) or imposition of UCMS (LZR) owing to increased ROS and TxA2 production. However, when OZR were exposed to UCMS, the severity of the depressive symptoms was increased, and dilator reactivity in conduit/resistance vessels was nearly ...

Chronic stress leads to many negative health outcomes proportional to the severity of developed depressive symptoms. This includes vascular reactivity, as endothelial function is compromised by 8 w...

Purpose: We reviewed our experience with carotid stenting (CS), focusing on technical evolution and results. Methods: From September 1995 to February 2000, 77 patients with 83 internal (n = 68) and common carotid artery lesions (n = 15) were selected for CS. This patient population was categorized into three consecutive periods based on patient selection, material, and technical skills. For internal carotid artery lesions, period I included 11 patients treated by means of direct carotid puncture with balloon expandable stents; period II included 42 patients treated by means of a femoral approach with self-expandable stents; and period III included 15 patients in whom monorail system and cerebral protection devices were used. Common carotid artery lesions were treated by means of carotid puncture in five patients and by means of a femoral approach in 10 patients. In only two of the latter cases, cerebral protection devices were used. Results: The overall immediate success rate, defined as successfully treated stenosis with no neurological events, was 89.7% for internal carotid artery lesions and 100% for common carotid artery lesions. All neurological events, which consisted of reversible events (4.4%), minor stroke (1.5%), and major stroke (2.9%), occurred during periods I and II. In periods I, II, and III, the rate of surgical conversion was 18%, 9.5%, and 0%, respectively, the rate of transient ischemic attack and reversible ischemic neurologic deficit was 0%, 7%, and 0%, respectively, and the rate of minor and major stroke was 0%, 7%, and 0%, respectively. All major strokes were cleared with intra-arterial thrombolysis. At discharge, the success rates defined by means of the absence of conversion and neurological events were 82% during period I, 76% during period II, and 100% during period III. The freedom from neurological deficits rates were 100%, 97.6%, and 100%, respectively. During follow-up, six significant asymptomatic restenoses were detected with duplex scanning; however, only one patient required reintervention. Conclusion: Technical skills and technological improvement, including low-profile balloon and catheter, cerebral protection device, and intra-arterial rescue techniques, may reduce the rate of neurological events associated with CS. Technical improvements should be given careful consideration before the initiation of randomized trials comparing CS and carotid endarterectomy. (J Vasc Surg 2001;33:1001-7.)

Purpose: To report endovascular repair of an iatrogenic superior mesenteric artery (SMA) dissection caused by a balloon occlusion catheter. Case Report: A 68-year-old man with a suprarenal aortic aneurysm underwent conventional prosthetic replacement, during which visceral artery back bleeding was controlled with balloon occlusion catheters. Six hours postoperatively, the patient experienced an episode of bloody diarrhea with abdominal pain and tenderness and mild metabolic acidosis. Colonoscopy revealed colitis (grade I) without necrosis of the right and left colon. An emergent abdominal computed tomographic scan showed signs of mesenteric ischemia with bowel dilatation and SMA wall hematoma; angiography identified a dissection 1 cm distal to the SMA origin. An Easy Wallstent was deployed percutaneously, successfully reestablishing SMA patency. The postoperative course was uneventful, and the patient remains asymptomatic with a patent SMA stent and aortic graft at 1 year. Conclusions: Iatrogenic SMA dissection should be suspected after suprarenal aortic aneurysm repair if signs of mesenteric ischemia arise. Prompt and thorough imaging studies are necessary to confirm the diagnosis and assess the potential for an endoluminal treatment.

Tracheal reconstruction after extensive resection remains an unsolved surgical problem. Numerous attempts have been made using tracheal grafts or prosthetic conduits with disappointing results. In this study, we propose a new alternative using an aortic autograft as tracheal substitute. In a first series of experiments, a half circumference of two rings was replaced with an autologous carotid artery patch. In a second series, a complete segment of trachea was replaced with an autologous aortic graft supported by an endoluminal tracheal stent. No dehiscence or stenosis was observed. Microscopic examinations at 3 and 6 months showed the replacement of the aortic tissue by tracheal tissue comprising neoformation of cartilage and mucociliary or non-keratinizing metaplastic polystratified squamous epithelium. Although these results need to be confirmed by a larger series of experiments, they showed that a vascular tissue placed in a different environment with a different function can be submitted to a metaplastic transformation which tends to restore a normal structure adapted to its new function. These remarkable findings offer new perspectives in tracheal reconstruction in human.

The focus of this chapter is limited to describing the embryology, anatomy, and physiology of the mes­enteric circulation. The terms mesenteric circulation and splanchnic circulation are sometimes used interchangeably; however, they have distinct meanings. The mesenteric circulation refers specifically to the vasculature of the intestines, whereas the splanchnic circulation provides blood flow to the entire abdominal portion of the digestive system that includes the hepatobiliary system, spleen, and pancreas. The primitive gut comprises the foregut, midgut, and hindgut. The foregut is further divided into upper foregut (embryonic pharynx) and lower foregut, which includes the esophagus, stomach, and the descending portion of the duodenum together with the hepatobiliary derivatives. By convention, the boundaries of the specific segments of the gut are determined by the three unpaired abdominal aortic trunks. The celiac axis supplies the abdominal foregut and its accessory organs, which include the abdominal esophagus, stomach, and proximal duo­denum, along with the hepatobiliary, pancreatic structures and spleen. The superior mesenteric artery supplies the midgut, which begins just distal to the ampulla of Vater and extends to the proximal two-thirds of the transverse colon. The inferior mesenteric artery supplies the hindgut, which includes the distal third of the transverse colon, the descending colon, and the rectum, and extends to the upper part of the anal canal. However, studies have shown that demarcation of these specific segments of the gut occurs well before the development of these vessels and depends on specific gene expression within the gut.

Depression is recognized as a predictor of increased cardiac morbidity and mortality. In addition, depressed patients exhibit an increase in the serum markers of endothelial dysfunction and platelet activation involved in the cascade of events leading to atherosclerosis. The purpose of this study was to determine the early and late-onset expression of various vascular markers in a rodent model of depression. Male DBA (an inbred strain of mice)/2J mice were exposed to either 7 weeks of controlled living conditions or unpredictable chronic mild stress (UCMS), and subsequently given daily fluoxetine (10 mg/kg) or NaCl (9%) during the last 5 weeks of the experiment. Depressive-like behavior was evaluated by using motivational and self-care behavior, including the assessment of the animal's coat state and grooming behavior. Enzyme-linked immunoassay was used to quantify matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and plasminogen activator inhibitor-1 (PAI-1) expression either immediately after the end of the UCMS procedure (short term condition) or 10 months later (long-term condition). Results indicate that 1) UCMS procedure induces a short-term depressive-like behavior in mice, defined as coat state deterioration, an effect that is prevented by fluoxetine treatment; 2) UCMS procedure has no effect on the short-term expression of the studied markers; however, UCMS increases expression of plasminogen activator inhibitor-1 only in the long-term group; 3) fluoxetine treatment is unable to counteract this UCMS-induced change; 4) aging induces behavioral perturbation, defined as a decrease in grooming motivation, and an increase of all the vascular markers in both control and UCMS groups and 5) pretreatment with fluoxetine has no protective effects on aging-induced behavioral and vascular alterations. Thus, in this model of depression-like behavior, UCMS appears to induce late-onset physiological changes, which are consistent with human studies indicating that depression is a risk factor for the development of heart disease.

Major depression is an independent risk factor for the development of cardiovascular disease. This impact of depression on vascular function seems to be mediated by the endothelial dysfunction, defined as an impairment of endothelium-dependent vasorelaxation, which represents a reliable predictor of atherosclerosis and has been regularly found to be associated with depression. This study aimed at investigating aortic vascular reactivity in mice submitted to the unpredictable chronic mild stress (UCMS) procedure, a reliable model of depression. The results confirm the effectiveness of the UCMS procedure to induce neuroendocrine, physical and behavioral depression-like alterations as well as a significant decrease of acetylcholine-induced vasorelaxation without any effect on phenylephrine-induced vasoconstriction. In this study, we reveal an altered vascular reactivity in an animal model of depression, demonstrating an endothelial dysfunction reminiscent to the one found in depressed patients.

One clinical intervention against the negative outcomes associated with atherothrombotic vascular disease (AVD) is low-dose, chronic aspirin therapy. However, epidemiological studies suggest that recurrence of adverse vascular events with aspirin therapy is growing and associated with therapy duration. The contributors to this outcome are unclear and include poor patient compliance and aspirin-resistant platelet thromboxane A2 (TxA2) production. Based on previous results in hypercholesterolemic mice, we hypothesized that elevated aspirin-insensitive arachidonic acid (AA)-induced TxA2 production by the vascular endothelium contributes to aspirin resistance in AVD independent of platelet behavior. AA-induced dilation was blunted in aortic rings and in arterioles from apolipoprotein E (ApoE) and low-density lipoprotein receptor (LDLR) gene deletion mice (vs. C57/Bl6/J), partially due to elevated TxA2 production. Acute inhibition of cyclooxygenases or TxA2 synthase attenuated the increased TxA2 production in ApoE and LDLR and improved AA-induced dilation, responses that were mirrored by chronic treatment with low-dose aspirin of 16 wk duration. However, this effect was not temporally stable, and, with longer-duration therapy, the beneficial impact of aspirin on outcomes diminished. A similar, though less robust, pattern to the impact of chronic aspirin therapy on vascular outcomes was identified with chronic antioxidant treatment (TEMPOL). These results suggest that in dyslipidemic mice, the beneficial impact of chronic aspirin therapy on improving vascular outcomes decay with time and that a contributing element to subsequent negative vascular events may be the development of aspirin-resistant TxA2 production by the vasculature itself.

As chronic stress and depression have become recognized as significant risk factors for peripheral vascular disease in patients with no prior history of vasculopathy, we interrogated this relationship utilizing an established mouse model of chronic stress/depressive symptoms from behavioral research. Male mice were exposed to 8 wk of unpredictable chronic mild stress (UCMS; e.g., wet bedding, predator sound/smell, random disruption of light/dark cycle), with indexes of depressive behavior (coat status, grooming, and mobility) becoming exacerbated vs. controls. In vascular rings, constrictor (phenylephrine) and endothelium-independent dilator (sodium nitroprusside) responses were not different between groups, although endothelium-dependent dilation (methacholine) was attenuated with UCMS. Nitric oxide synthase (NOS) inhibition was without effect in UCMS but nearly abolished reactivity in controls, while cyclooxygenase inhibition blunted dilation in both. Combined blockade abolished reactivity in controls, although a significant dilation remained in UCMS that was abolished by catalase. Arterial NO production was attenuated by UCMS, although H2O2 production was increased. UCMS mice demonstrated an increased, although variable, insulin resistance and inflammation. However, while UCMS-induced vascular impairments were consistent, the predictive power of aggregate plasma levels of insulin, TNF-α, IL-1β, and C-reactive peptide were limited. However, when separated into tertiles with regard to vascular outcomes, insulin resistance and hypertension were predictive of the most severe vascular impairments. Taken together, these data suggest that aggregate insulin resistance, inflammation, and hypertension in UCMS mice are not robust predictors of vascular dysfunction, suggesting that unidentified mechanisms may be superior predictors of poor vascular outcomes in this model.

Genetic familial hypercholesterolemia (FH) and combined hyperlipidemia (FCH) are characterized by elevated plasma low-density lipoprotein (LDL) (FH) and LDL/triglycerides (FCH), with mouse models represented by LDL receptor (LDLR) and apolipoprotein E (ApoE) gene deletion mice, respectively. Given the impact of FH and FCH on health outcomes, we determined the impact of FH/FCH on vascular structure in LDLR and ApoE mice. LDLR, ApoE and control mice were utilized at 12-13 and 22-23 weeks when gracilis arteries were studied for wall mechanics and gastrocnemius muscles were harvested for microvessel density measurements. Conduit arteries and plasma samples were harvested for biochemical analyses. Arteries from ApoE and LDLR exhibited blunted expansion versus control, reduced distensibility and left-shifted stress versus strain relation (LDLR > ApoE). Microvessel density was reduced in ApoE and LDLR (ApoE > LDLR). Secondary analyses suggested that wall remodeling in LDLR was associated with cholesterol and MCP-1, while rarefaction in ApoE was associated with tumor necrosis factors-alpha, triglycerides and vascular production of TxA(2). Remodeling in ApoE and LDLR appears distinct; as that in LDLR is preferential for vascular walls, while that for ApoE is stronger for rarefaction. Remodeling in LDLR may be associated with cellular adhesion, while that in ApoE may be associated with pro-apoptotsis and constrictor prostanoid generation.

The aim of this study was to determine if arachidonic acid (AA)-induced skeletal muscle arteriolar dilation is altered with hypercholesterolemia in ApoE and low-density lipoprotein receptor (LDLR) gene deletion mice fed a normal diet. This study also determined contributors to altered AA-induced dilation between dyslipidemic mice and controls, C57/Bl/6J (C57).Gracilis muscle arterioles were isolated, with mechanical responses assessed following a challenge with AA under control conditions and after elements of AA metabolism pathways were inhibited. Conduit arteries from each strain were used to assess AA-induced production of PGI(2) and TxA(2).Arterioles from ApoE and LDLR exhibited a blunted dilation to AA versus C57. While responses were cyclo-oxygenase-dependent in all strains, inhibition of thromboxane synthase or blockade of PGH(2)/TxA(2) receptors improved dilation in ApoE and LDLR only. AA-induced generation of PGI(2) was comparable across strains, although TxA(2) generation was increased in ApoE and LDLR. Arteriolar reactivity to PGI(2) and TxA(2) was comparable across strains. Treatment with TEMPOL improved dilation and reduced TxA(2) production with AA in ApoE and LDLR.These results suggest that AA-induced arteriolar dilation is constrained in ApoE and LDLR via an increased production of TxA(2). While partially due to elevated oxidant stress, additional mechanisms contribute that are independent of acute alterations in oxidant tone.

Measurement of flow-mediated vasodilatation (FMD) in brachial and other conduit arteries has become a common method to asses the status of endothelial function in vivo. In spite of the direct relationship between the arterial wall multi-component strains and FMD responses, direct measurement of wall strain tensor due to FMD has not yet been reported in the literature. In this work, a noninvasive direct ultrasound-based strain tensor measuring (STM) technique is presented to assess changes in the mechanical parameters of the vascular wall during FMD. The STM technique utilizes only sequences of B-mode ultrasound images, and starts with segmenting a region of interest within the artery and providing the acquisition parameters. Then a block matching technique is employed to measure the frame to frame local velocities. Displacements, diameter change, multi-component strain tensor and strain rates are then calculated by integrating or differentiating velocity components. The accuracy of the STM algorithm was assessed using a phantom study, and was further validated using in vivo data from human subjects. Results indicate the validity and versatility of the STM algorithm, and describe how parameters other than the diameter change are sensitive to pre- and post-occlusion, which can then be used for accura te assessment of atherosclerosis. Keywords: Atherosclerosis; Vascular Wall Mechanics; Flow Me diated Vasodilatation; Strain Tensor Measurement

Objective: Surgical revascularization is the standard treatment of complex blunt traumatic extremity vascular injuries. Limb salvage may be improved with minimally invasive endovascular therapies because of the ability to perform diagnostic and therapeutic intervention simultaneously. Two cases of acute limb-threatening arterial injuries successfully treated with percutaneous endovascular therapy are reported. Results: A skier suffered hemodynamic instability after shoulder reduction. An axillary arterial injury was suspected and confirmed with angiography. A covered stent successfully controlled the hemorrhage. A morbidly obese female sustained anterior dislocation of her left knee 7 years previously requiring repair. She developed recurrent knee dislocation with acute leg ischemia. Emergent fixation was performed followed by percutaneous angiography. Short segment thrombosis of the popliteal was noted. Wire recanalization of the thrombosed artery and stent placement restored 3-vessel runoff. Conclusion: Endovascular therapy can offer faster, easier access to the extremity vascular injury facilitating revascularization and avoiding long incisions and dissections.

Eur J Vasc Endovasc Surg 25, 180–184 (2003)

Chronic non-healing foot wounds are common complication in the diabetic population. Local radiant heat bandage has recently been proposed as an effective adjuvant. The purpose of this study was to evaluate the efficacy of such bandage in controlling infection in an ovine ischemic wound model.Bilateral flank ischemic wounds were created in a total of 42 sheep. 14 sheep were challenged with Pseudomonas aeruginosa (PA), 13 with Escherichia Coli (EC), and 15 with Methicillin resistant staphylococcus aureus (MRSA). The left flank was designated the treatment side and the right the control side. The radiant heat bandage was applied for a total of 10 days. The animal were then euthanized and the wounds harvested for bacterial quantification.39 sheep completed the study. Mean bacterial counts were has follows: for MRSA, control 7.6 x 10(5) CFU/gm vs. heated 2.0 x 10(5) CFU/gm (p=0.16); for EC, control 1.1 x 10(6) CFU/gm vs. heated 2.7 x 10(5) CFU/gm (p=0.006); PA, control 1.7 x 10(6) CFU/gm vs. heated 3.9 x 10(9) CFU/gm (p=0.001).Non-contact radiant bandages controls bacterial growth in ischemic wounds infected with MRSA or EC and may potentially improve wound healing. Wounds infected with PA should no be submitted to such treatment.

Hypothesis: Supplemental oxygen can reduce intimal hyperplasia (IH) after stent deployment in a rabbit model. Background: Endovascular stent placement is technically feasible, but long-term durability in vessels outside the aortoiliac system is compromised with postinterventional IH, which causes restenosis and failure of the arterial conduit. Methods: Groups (n = 4 to 6) of female New Zealand white rabbits underwent placement of a 3-mm intraaortic stent with laparotomy and were placed in either normoxic (21% inspired oxygen concentration) or supplemental-oxygen (40% inspired oxygen concentration) environments for 0, 7, 14, and 28 days. The transarterial wall oxygen gradient was measured at 0, 7, and 28 days with an oxygen microelectrode. 5-Bromo-2'deoxyuridine (BrdU) was injected into the peritoneum before death to assess cellular proliferation. Aortic specimens were harvested en bloc and sectioned for analysis of cellular proliferation and intimal thickness. Results: Intraaortic stent placement significantly decreased the transarterial wall oxygen gradient in the outer 70% of the vessel wall and was easily reversed at 7, 14, and 28 days with application of supplemental oxygen. Cellular proliferation was significantly decreased at 14 days (0.5% ± 0.001% versus 2.3% ± 0.002%; P