Clinical significance of reversal of flow in the vertebral artery identified on cerebrovascular duplex ultrasound.

BACKGROUND: Reversal of flow in the vertebral artery (RFVA) is an uncommon finding on cerebrovascular duplex ultrasound examination. The clinical significance of RFVA and the natural history of patients presenting with it are poorly understood. Our objective was to better characterize the symptoms and outcomes of patients presenting with RFVA. METHODS: A retrospective review was performed of all cerebrovascular duplex ultrasound studies performed at our institution between January 2010 and January 2016 (N = 2927 patients). Individuals with RFVA in one or both vertebral arteries were included in the analysis. RESULTS: Seventy-four patients (74/2927 patients [2.5%]) with RFVA were identified. Half of the patients were male. Mean age at the time of the first ultrasound study demonstrating RFVA was 71 years (range, 27-92 years); 78% of patients had hypertension, 28% were diabetic, and 66% were current or former smokers. Indications for the ultrasound examination were as follows: 44% screening/asymptomatic, 7% anterior circulation symptoms, 20% posterior circulation symptoms, 28% follow-up studies after cerebrovascular intervention, and 5% upper extremity symptoms. At the time of the initial ultrasound examination, 21 patients (28%) had evidence of a prior carotid intervention (carotid endarterectomy or carotid stenting), 21 patients had evidence of moderate (50%-79%) carotid artery stenosis (CAS) in at least one carotid artery, and 12 patients (16%) had evidence of severe (>80%) CAS. Of the 15 patients presenting with posterior circulation symptoms, 11 (73%) had evidence of concomitant CAS. In contrast, 22 of the 59 patients (37%) without posterior circulation symptoms had duplex ultrasound findings of CAS (P = .01). The mean duration of follow-up was 28 ± 22 months. Follow-up data were available for 63 patients (85%), including the 15 patients who presented with posterior circulation symptoms. Of these 15 patients, 5 underwent subclavian artery revascularization, including balloon angioplasty and stenting in 4 patients and open/hybrid revascularization in 1 patient. Five individuals were awaiting intervention. Three patients underwent carotid endarterectomy for CAS, with resultant improvement in posterior circulation symptoms. Finally, one patient was deemed too high risk for intervention, and one patient was found to have an alternative cause for symptoms. The remaining 59 patients continued to be asymptomatic during follow-up. One patient progressed to vertebral artery occlusion, and six patients had progression of CAS. CONCLUSIONS: Symptomatic RFVA responds well to intervention, including subclavian artery stenting and carotid intervention in patients with CAS. The majority of patients with this finding are asymptomatic at the time of presentation. Although progression of vertebral artery disease is rare, these patients may benefit from monitoring for progression of CAS with surveillance ultrasound.

Idiopathic Carotidynia.

Idiopathic carotidynia is a syndrome characterized by pain and tenderness over the carotid artery without an associated structural luminal abnormality. Controversy exists over whether this is a distinct disease entity or merely a symptom attributable to other causes of neck pain, such as carotid dissection or vasculitis. A 50-year-old woman presented with sudden-onset right neck pain. Imaging studies demonstrated transmural inflammation of the proximal internal carotid artery, without evidence of intraluminal pathology. The patient was placed on low-dose aspirin and ibuprofen. Her symptoms resolved within a week. At 3-month follow-up, her carotid artery appeared normal on duplex ultrasonography.

Novel association between bone mineral density scores and the prevalence of peripheral artery disease in both sexes.

The purpose of the current study was to investigate the association between bone mineral density (BMD) scores and the prevalence of peripheral artery disease (PAD) in a large cohort of subjects who underwent arterial Doppler assessments and calcaneal bone densitometry. The study was performed using data obtained from Life Line Screening Inc. Subjects were self-selected and paid for screening tests. The prevalence of PAD was significantly higher in men with osteopenia (4.5%) and osteoporosis (10.9%) compared to men with normal BMD (3.0%) ( p<0.001). Osteopenia (odds ratio (OR) 1.3) and osteoporosis (OR 2.3) were found to be independent risk factors for the presence of PAD in men. The prevalence of PAD was significantly higher in women with osteopenia (4.8%) and osteoporosis (11.8%) compared to women with normal BMD (3.3%) ( p<0.001). Osteopenia (OR 1.15) and osteoporosis (OR 1.8) were found to be independent risk factors for the presence of PAD in women. The current study reports a strong association of abnormal BMD analysis with the prevalence of PAD, which persists even when controlling for age and associated atherosclerotic risk factors. Although the mechanism by which these two disease processes is related is not completely elucidated, the presence of osteoporosis should make clinicians aware of the possibility of occult PAD or associated atherosclerotic disease in appropriate patients.

Endovascular Treatment of Nutcracker Syndrome.

BACKGROUND: Nutcracker syndrome, or mesoaortic compression of the left renal vein (LRV), with associated symptoms related to venous hypertension in the left kidney, is a rare entity that may result in severe symptoms requiring operative intervention. We report on 3 patients who presented with nutcracker syndrome, including one patient with a circumaortic LRV resulting in posterior nutcracker syndrome, who underwent successful endovascular treatment with renal vein stenting. A review of existing literature on endovascular management of nutcracker syndrome follows. METHODS: Three women (age range 28-43 years) presented with symptoms and imaging studies consistent with nutcracker syndrome. Symptoms included pelvic and flank pain in all 3 patients, and episodes of hematuria in 2 patients. Imaging studies demonstrated compression of the LRV between the superior mesenteric artery and aorta in 2 of the patients. The third patient was noted to have a circumaortic LRV. RESULTS: All 3 patients underwent venography and LRV stenting. Stents included a 12 × 40 mm self-expanding nitinol stent, 14 × 60 mm WALLSTENT, and 16 × 40 mm WALLSTENT. All patients were placed on clopidogrel postoperatively. The duration of follow-up ranged from 6 to 27 months. At follow-up, all 3 patients reported significant symptomatic improvement, and duplex ultrasonography demonstrated stent patency in all. CONCLUSIONS: Nutcracker syndrome is a rare condition that can be successfully treated with renal vein stenting via an endovascular approach. Results are encouraging at follow-up periods beyond 2 years.

Autologous human plasma in stem cell culture and cryopreservation in the creation of a tissue-engineered vascular graft.

OBJECTIVE: Previous work demonstrated the effectiveness of autologous adipose-derived stem cells (ASCs) as endothelial cell (EC) substitutes in vascular tissue engineering. We further this work toward clinical translation by evaluating ASC function after (1) replacement of fetal bovine serum (FBS) with autologous human plasma (HP) in culture and (2) cryopreservation. METHODS: Human ASCs and plasma, isolated from periumbilical fat and peripheral blood, respectively, were collected from the same donors. ASCs were differentiated in endothelial growth medium supplemented with FBS (2%) vs HP (2%). Proliferation was measured by growth curves and MTT assay. Endothelial differentiation was measured by quantitative polymerase chain reaction, assessment of acetylated low-density lipoprotein uptake, and cord formation after plating on Matrigel (BD Biosciences, San Jose, Calif). Similar studies were conducted before and after cryopreservation of ASCs and included assessment of cell retention on the luminal surface of a vascular graft. RESULTS: ASCs expanded in HP-supplemented medium showed (1) similar proliferation to FBS-cultured ASCs, (2) consistent differentiation toward an EC lineage (increases in CD31, von Willebrand factor, and CD144 message; acetylated low-density lipoprotein uptake; and cord formation on Matrigel), and (3) retention on the luminal surface after seeding and subsequent flow conditioning. Cryopreservation did not significantly alter ASC viability, proliferation, acquisition of endothelial characteristics, or retention after seeding onto a vascular graft. CONCLUSIONS: This study suggests that (1) replacement of FBS with autologous HP--a step necessary for the translation of this technology into human use--does not significantly impair proliferation or endothelial differentiation of ASCs used as EC substitutes and (2) ASCs are tolerant to cryopreservation in terms of maintaining EC characteristics and retention on a vascular graft.

Vascular control for a forequarter amputation of a massive fungating humeral osteosarcoma.

Forequarter amputation is a radical operation performed for treatment of malignant neoplasms of the shoulder girdle not amenable to limb salvage. Traditional approaches involve bone and soft tissue resection, followed by ligation of the axillary vessels. We describe a technique to minimize blood loss whereby control of the subclavian vessels is performed before amputation of a large tumor associated with extensive venous congestion. A 34-year-old man presented with proximal humeral osteosarcoma. Surgery involved claviculectomy to facilitate vascular control of the subclavian vessels, followed by guillotine amputation at the proximal upper arm level and completion of the amputation as conventionally described.

Iliac Artery-Uretero-Colonic Fistula Presenting as Severe Gastrointestinal Hemorrhage and Hematuria: A Case Report and Review of the Literature.

Arterioenteric fistulas represent an infrequent but potentially fatal cause of gastrointestinal hemorrhage. Patients often present in extremis from shock and sepsis. This mandates a rapid diagnosis so that prompt, potentially life-saving interventions can be performed. We report the case of a 35-year-old man who presented with hematuria and hematochezia secondary to an iliac artery-uretero-colonic fistula that developed years after open common iliac artery aneurysm repair. His condition rapidly progressed to hemorrhagic shock, and he underwent successful endovascular treatment with a covered stent graft as a bridge to definitive open surgery. Subsequently, graft explantation, extra-anatomic arterial bypass, bowel resection, and ureter ligation was undertaken. A summary of the literature on iliac artery-enteric fistulas follows.

eNOS transfection of adipose-derived stem cells yields bioactive nitric oxide production and improved results in vascular tissue engineering.

This study evaluates the durability of a novel tissue engineered blood vessel (TEBV) created by seeding a natural vascular tissue scaffold (decellularized human saphenous vein allograft) with autologous adipose-derived stem cells (ASC) differentiated into endothelial-like cells. Previous work with this model revealed the graft to be thrombogenic, likely due to inadequate endothelial differentiation as evidenced by minimal production of nitric oxide (NO). To evaluate the importance of NO expression by the seeded cells, we created TEBV using autologous ASC transfected with the endothelial nitric oxide synthase (eNOS) gene to produce NO. We found that transfected ASC produced NO at levels similar to endothelial cell (EC) controls in vitro which was capable of causing vasorelaxation of aortic specimens ex vivo. TEBV (n = 5) created with NO-producing ASC and implanted as interposition grafts within the aorta of rabbits remained patent for two months and demonstrated a non-thrombogenic surface compared to unseeded controls (n = 5). Despite the xenograft nature of the scaffold, the TEBV structure remained well preserved in seeded grafts. In sum, this study demonstrates that upregulation of NO expression within adult stem cells differentiated towards an endothelial-like lineage imparts a non-thrombogenic phenotype and highlights the importance of NO production by cells to be used as endothelial cell substitutes in vascular tissue engineering applications.

Endothelial differentiation of diabetic adipose-derived stem cells.

BACKGROUND: Diabetic (DM) patients frequently lack autologous vascular tissue required for revascularization procedures and dialysis access creation. We have developed a tissue-engineered graft that uses adipose-derived stem cells (ASC) as endothelial cell substitutes. Here, we compare DM versus nondiabetic (NDM) ASC in terms of isolation efficiency, proliferation, commitment toward endothelial lineage, and seeding onto the luminal surface of a graft. METHODS: ASC were isolated from liposuction specimens of vascular surgery patients. Proliferation was assessed by constructing growth curves over 14 d. ASC were differentiated in endothelial growth medium (EGM2). Endothelial commitment was assessed by measuring endothelial cell-specific gene expression (CD31, von Willebrand factor) and by cord formation on Matrigel. Finally, ASC were seeded onto a vascular scaffold, flow conditioned, and imaged with confocal microscopy. RESULTS: Diabetes did not alter ASC isolation efficiency (224,028 ± 20,231 cells/g adipose for DM (n = 53) versus 259,345 ± 15,441 cells/g adipose for NDM (n = 145; P = 0.21). Growth curves for DM (n = 6) and NDM (n = 6) also appeared similar. After culture in EGM2, upregulation of CD31 and von Willebrand factor message was observed in NDM; these markers were found within the primary cultures of DM but no upregulation was observed after culture in EGM2. Both groups exhibited similar cord formation on Matrigel and retention to vascular scaffolds. CONCLUSIONS: Isolation and proliferation studies suggest that adipose is a promising source of stem cells for tissue engineering in the DM population. The angiogenic potential of DM ASC appears intact; however, differences in acquisition of endothelial cell markers suggest that differentiation may be inhibited or delayed by diabetes.

Middle aortic coarctation.

BACKGROUND: Middle aortic coarctation (MAC), a variant of middle aortic syndrome, is a rare entity with only ∼200 cases described in the literature. It classically presents with early onset and refractory hypertension, abdominal angina, and lower extremity claudication. Although endovascular repair has been described for focal stenoses, open bypass remains the standard to restore abdominal inflow and correct renovascular hypertension. METHODS: We describe an unusually late presentation of MAC in a 52-year-old man from El Salvador with refractory hypertension since age 8 requiring 5 antihypertensive medications. He presented with acute chest pain and severe hypertension. He denied mesenteric and peripheral vascular symptoms. Distal pulses were not palpable. Creatinine was 1.9 mg/dL (peak 4.0 mg/dL). Computed tomography angiography demonstrated coarctation of the descending thoracic aorta with extensive collateralization. RESULTS: After control of blood pressure, the patient's singular anatomy dictated a descending thoracic aorta-infrarenal aortic bypass using a 16-mm woven Hemashield tube graft via a left fifth-interspace anterolateral thoracotomy and left retroperitoneal incision. The graft was tunneled through the posterior left hemidiaphragm. Patient had excellent recovery, with decrease in antihypertensive medications (5 to 2), restoration of all distal pulses, and no neurologic complications. Postoperative creatinine was 0.9 mg/dL. CONCLUSIONS: MACs are rare entities with presentation usually in youth or adolescence, comprising only 0.5-2% of all aortic coarctation cases. Etiologies include congenital, acquired, inflammatory, and infectious causes. If untreated, most patients do not survive past the fourth decade because of the sequelae of renovascular hypertension including myocardial infarction, heart failure, intracranial hemorrhage, and aortic rupture. Depending on technical considerations, open surgical bypass remains the standard repair for MAC.

Coral reef aorta: case report and review of the literature.

Coral reef aorta (CRA) is a rare form of atherosclerosis that affects the paravisceral and pararenal aorta and its branches. Patients typically present with arterial insufficiency of the bowels, kidneys and lower extremities. The current mainstay of treatment is operative, typically involving transaortic endarterectomy. Herein, we describe a 54-year-old woman with incapacitating lower extremity claudication secondary to a paravisceral coral reef atheroma treated successfully with transaortic endarterectomy via a left retroperitoneal approach. In addition, we present a complete review of modern English literature on CRA.

Treatment of bleeding varicose veins of the scrotum with percutaneous coil embolization of the left spermatic vein: a case report.

Percutaneous coil embolization of the spermatic vein offers a minimally invasive method for treating symptomatic varicose veins of the scrotum. We describe the case of a 63-year-old man with multiple comorbidities and persistent bleeding from scrotal varicosities. Venography revealed significant left spermatic vein reflux and a large left varicocele. Percutaneous coil embolization of the left spermatic vein completely resolved the bleeding from the left side of the patient's scrotum. Although many vascular specialists possess the technical skills to perform this procedure, they may not be familiar with its use in the treatment of scrotal varicosities and varicoceles.

Role of angiotensin II type 1A receptor phosphorylation, phospholipase D, and extracellular calcium in isoform-specific protein kinase C membrane translocation responses.

The angiotensin II type 1A receptor (AT(1A)R) plays an important role in cardiovascular function and as such represents a primary target for therapeutic intervention. The AT(1A)R is coupled via G(q) to the activation of phospholipase C, the hydrolysis of phosphoinositides, release of calcium from intracellular stores, and the activation of protein kinase C (PKC). We show here that PKCbetaI and PKCbetaII exhibit different membrane translocation patterns in response to AT(1A)R agonist activation. Whereas PKCbetaII translocation to the membrane is transient, PKCbetaI displays additional translocation responses: persistent membrane localization and oscillations between the membrane and cytosol following agonist removal. The initial translocation of PKCbetaI requires the release of calcium from intracellular stores and the activation of phospholipase C, but persistent membrane localization is dependent upon extracellular calcium influx. The mutation of any of the three PKC phosphorylation consensus sites (Ser-331, Ser-338, and Ser-348) localized within the AT(1A)R C-tail significantly increases the probability that persistent increases in diacylglycerol levels and PKCbetaI translocation responses will be observed. The persistent increase in AT(1A)R-mediated diacylglycerol formation is mediated by the activation of phospholipase D. Although the persistent PKCbetaI membrane translocation response is absolutely dependent upon the PKC activity-dependent recruitment of an extracellular calcium current, it does not require the activation of phospholipase D. Taken together, we show that the patterning of AT(1A)R second messenger response patterns is regulated by heterologous desensitization and PKC isoform substrate specificity.