Aorta-innominate bypass through ministernotomy.

Atherosclerotic innominate artery occlusive disease can lead to cerebral and upper extremity ischemia. Innominate artery angioplasty and stenting can be complicated by stent fractures and restenosis; furthermore, this technique is limited in treatment of innominate artery occlusions. Ministernotomy to the second or third intercostal space can be used instead of conventional full sternotomy for open surgical revascularization of the innominate artery with excellent perioperative and long-term outcomes. This series of three consecutive patients highlights the technique of aorta-innominate artery bypass through ministernotomy.

Hybrid Endovascular Aortic Aneurysm Repair: Preservation of Pelvic Perfusion with External to Internal Iliac Artery Bypass.

BACKGROUND: Diminished pelvic arterial flow as a result of intentional coverage/embolization of internal iliac arteries (IIA) during isolated endovascular common iliac artery aneurysm (CIAA) repair or endovascular repair of abdominal aortic aneurysms (EVAR) may result in symptomatic pelvic ischemia. Although generally well tolerated, in severe cases, pelvic ischemia may manifest as recalcitrant buttock claudication, vasculogenic impotence, or perineal, vesicle, rectal, and/or spinal cord ischemia. Branched graft technology has recently become available; however, many patients are not candidates for endovascular repair with these devices. Therefore, techniques to preserve pelvic arterial flow are needed. We reviewed our outcomes of isolated endovascular CIAA repair or EVAR in conjunction with unilateral external-internal iliac artery bypass. METHODS: Single-center, retrospective review of 10 consecutive patients who underwent hybrid endovascular abdominal aortic aneurysm (AAA) or CIAA repair with concomitant external-internal iliac artery bypass between 2006 and 2015. Demographics, index procedural details, postoperative symptoms, hospital length of stay (LOS), follow-up imaging, and bypass patency were recorded. RESULTS: The cohort of 10 patients was all men with a mean age of 71 years (range: 56-84). Hybrid repair consisted of contralateral IIA coil embolization followed by EVAR with external iliac artery-internal iliac artery (EIA-IIA) bypass. All EIA-IIA bypasses were performed via a standard lower quadrant retroperitoneal approach with a prosthetic bypass graft. Technical success was 100%, and there were no perioperative deaths. One patient developed transient paraplegia, 1 patient had buttock claudication on the side of his hypogastric embolization contralateral to his iliac bypass, and 1 developed postoperative impotence. 20% of patients sustained long-term complications (buttock claudication and postoperative impotence). Mean LOS was 2.8 days (range: 1-9 days). Postoperative imaging was obtained in 90% of patients, and mean follow-up was 10.8 months (range: 0.5-36 months). All bypasses remained patent. CONCLUSIONS: Although branched graft technology continues to evolve, strategies to maintain adequate pelvic circulation are necessary to avoid the devastating complications of pelvic ischemia. We have demonstrated that a hybrid approach combining EVAR or isolated endovascular common iliac artery exclusion with a unilateral external-internal iliac bypass via a retroperitoneal approach is well tolerated with a short LOS and excellent patency rates.

The enduring patency of primary inferior vena cava repair.

BACKGROUND: Inferior vena cava repair after planned and unplanned venotomy is performed by either interposition bypass, patch venopasty, or lateral venorrhaphy and primary repair. Primary repair of the inferior vena cava avoids the use of foreign material and allows an all-autologous repair in an expeditious fashion. The purpose of this study was to demonstrate the utility of inferior vena cava repair, determine the degree of inferior vena cava stenosis, and examine clinical outcomes after primary repair. METHODS: We conducted a single-center retrospective review of patients who underwent primary inferior vena cava repairs between January 2002 and January 2014 at a tertiary care center. Primary repair followed lateral venorrhaphy for tumor extraction or for repair of an iatrogenic inferior vena cava injury. Patient demographics, cross-sectional vena cava dimensions, and patient outcomes were tabulated. RESULTS: In total, 47 (30 men and 17 women) patients underwent primary inferior vena cava repair (median age 58 years, range 31-83 years). Twenty-six patients (15 men and 11 women) underwent en bloc radical nephrectomy, inferior vena cava tumor thrombus extraction, and primary lateral venorrhaphy (median age 61 years, range 39-83 years). The majority, 92% of these patients, had renal cell carcinoma on final pathology, with a median follow-up period of 39 months (range 1-108 months). Twenty-one patients (15 men and 6 women) underwent primary repair for iatrogenic inferior vena cava injury (median age 54 years, range 31-82 years). The median follow-up period was 18.5 months (3-110 months). Clinic follow-up with postoperative imaging was obtained in 76.9% of those undergoing tumor thrombus extraction (n = 20) and 76.2% of those undergoing repair of an iatrogenic injury (n = 16). Overall, there was a 13% infrarenal inferior vena cava diameter loss, 17% inferior vena cava diameter loss at the level of the renal veins, and 10% suprarenal inferior vena cava diameter loss when comparing postoperative with preoperative imaging. All patients remained asymptomatic; therefore, inferior vena cava narrowing associated with primary repair was clinically insignificant. CONCLUSION: Primary inferior vena cava repair is associated with less than 20% inferior vena cava diameter loss and does not compromise venous outflow from the extremities. Primary inferior vena cava repair is a safe and expeditious technique that provides excellent clinical outcomes and long-term patency.

Periadventitial adipose tissue modulates the effect of PROLI/NO on neointimal hyperplasia.

BACKGROUND: Periadventitial delivery of nitric oxide (NO) inhibits neointimal hyperplasia; however, the effect of periadventitial adipose tissue on the efficacy of NO at inhibiting neointimal hyperplasia has not been studied. The aim of our study was to assess the effect of NO in the presence and absence of periadventitial adipose tissue. We hypothesized that removal of periadventitial adipose tissue will increase neointimal formation and that NO will be more effective at inhibiting neointimal hyperplasia. METHODS: The effect of NO on 3T3 fibroblasts, adventitial fibroblast (AF), and vascular smooth muscle cell (VSMC) proliferation was assessed by (3)H-thymidine incorporation in adipocyte-conditioned or regular media. The rat carotid artery balloon injury model was performed on male Sprague-Dawley rats. Before balloon injury, periadventitial adipose tissue was removed (excised model) or remained intact (intact model). Treatment groups included injury or injury with periadventitial application of PROLI/NO. Adiponectin receptor (AR) levels were assessed via immunofluorescence. RESULTS: Adipocyte-conditioned media had an antiproliferative effect on 3T3 and AF and a proproliferative effect on VSMC in vitro. Interestingly, NO was less effective at inhibiting 3T3 and AF proliferation and more effective at inhibiting VSMC proliferation in adipocyte-conditioned media. In vivo, the excised group showed increased neointimal hyperplasia 2 wk after surgery compared with the intact group. NO reduced neointimal hyperplasia to a greater extent in the excised group compared with the intact group. Although NO inhibited or had no impact on AR levels in the intact group, NO increased AR levels in media and adventitia of the excised group. CONCLUSIONS: These data show that periadventitial adipose tissue plays a role in regulating the arterial injury response and the efficacy of NO treatment in the vasculature.

Fifteen-year experience with renal cell carcinoma with associated venous tumor thrombus.

BACKGROUND: For patients with renal cell carcinoma with venous tumor thrombus (VTT), the importance of the extent of the VTT on survival has inconsistent published results. The aim of the study was to evaluate the prognostic value of the VTT on morbidity and mortality of our patients with renal cell carcinoma. METHODS: This was a single institution review of all patients who underwent resection of renal cell carcinoma with VTT over a 15-year period. RESULTS: Thirty-seven patients (26 men, 11 women) with a mean age of 61 years were analyzed. The majority of the cohort were of Neves level II (n = 19), while 8 were of Neves 0 (only renal vein) or I, and 10 were of Neves III (extending into retrohepatic cava) or IV (extending supradiaphragmatically). When compared with Neves 0-II patients, there were more Neves III-IV patients with operative time >3 hours (70% vs 30%), blood loss >2,000 mL (70% vs 33%), and intensive care unit stay longer than one day (60% vs 30%) (P ≤ .05 each). Mean follow-up was 58 months. The overall 5-year survival was 71%, and all 10 patients with Neves III-IV had survived since the operation. CONCLUSION: We found advanced tumor thrombus involvement did not impact long-term survival; however, cases with suprahepatic VTT had increased operative time, blood loss, and duration of hospital stay.

Two Cases of Aortic Intimal Intussusception During Endovascular Repair of an Acute Type B Dissection.

PURPOSE: To raise awareness of a previously undescribed complication of thoracic endovascular aortic repair (TEVAR) for aortic dissection that can lead to acute aortic occlusion and to highlight that early recognition, excision of the intimal flap, and open aortic repair can be lifesaving. CASE REPORT: Two patients underwent TEVAR for acute type B dissections complicated by abdominal malperfusion syndrome. During stent-graft deployment, the intimal flap circumferentially detached from its origin proximally with subsequent intussusception, leading to acute aortic occlusion. Both complications were recognized intraoperatively with immediate conversion to open aortic reconstruction and intimal flap excision. The first patient required an infrarenal aortobi-iliac bypass, while the second had an open aortic fenestration and bovine pericardial patch repair of the aortotomy. Their postoperative courses were uneventful. Follow-up imaging revealed excellent stent-graft approximation without endoleak and thrombosis of the false lumen. CONCLUSION: Aortic intimal flap detachment and intussusception is a rare but potentially fatal complication of TEVAR for acute complicated aortic dissection. Quick diagnosis and a low threshold for conversion to open repair are critical in achieving a successful outcome.

Sex-based differential regulation of oxidative stress in the vasculature by nitric oxide.

BACKGROUND: Nitric oxide ((•)NO) is more effective at inhibiting neointimal hyperplasia following arterial injury in male versus female rodents, though the etiology is unclear. Given that superoxide (O2(•-)) regulates cellular proliferation, and (•)NO regulates superoxide dismutase-1 (SOD-1) in the vasculature, we hypothesized that (•)NO differentially regulates SOD-1 based on sex. MATERIALS AND METHODS: Male and female vascular smooth muscle cells (VSMC) were harvested from the aortae of Sprague-Dawley rats. O2(•-) levels were quantified by electron paramagnetic resonance (EPR) and HPLC. sod-1 gene expression was assayed by qPCR. SOD-1, SOD-2, and catalase protein levels were detected by Western blot. SOD-1 activity was measured via colorimetric assay. The rat carotid artery injury model was performed on Sprague-Dawley rats ±(•)NO treatment and SOD-1 protein levels were examined by Western blot. RESULTS: In vitro, male VSMC have higher O2(•-) levels and lower SOD - 1 activity at baseline compared to female VSMC (P < 0.05). (•)NO decreased O2(•-) levels and increased SOD - 1 activity in male (P<0.05) but not female VSMC. (•)NO also increased sod- 1 gene expression and SOD - 1 protein levels in male (P<0.05) but not female VSMC. In vivo, SOD-1 levels were 3.7-fold higher in female versus male carotid arteries at baseline. After injury, SOD-1 levels decreased in both sexes, but (•)NO increased SOD-1 levels 3-fold above controls in males, but returned to baseline in females. CONCLUSIONS: Our results provide evidence that regulation of the redox environment at baseline and following exposure to (•)NO is sex-dependent in the vasculature. These data suggest that sex-based differential redox regulation may be one mechanism by which (•)NO is more effective at inhibiting neointimal hyperplasia in male versus female rodents.

Nitric oxide inhibits neointimal hyperplasia following vascular injury via differential, cell-specific modulation of SOD-1 in the arterial wall.

Superoxide (O2(•-)) promotes neointimal hyperplasia following arterial injury. Conversely, nitric oxide ((•)NO) inhibits neointimal hyperplasia through various cell-specific mechanisms, including redox regulation. What remains unclear is whether (•)NO exerts cell-specific regulation of the vascular redox environment following arterial injury to inhibit neointimal hyperplasia. Therefore, the aim of the present study was to assess whether (•)NO exerts cell-specific, differential modulation of O2(•-) levels throughout the arterial wall, establish the mechanism of such modulation, and determine if it regulates (•)NO-dependent inhibition of neointimal hyperplasia. In vivo, (•)NO increased superoxide dismutase-1 (SOD-1) levels following carotid artery balloon injury in a rat model. In vitro, (•)NO increased SOD-1 levels in vascular smooth muscle cells (VSMC), but had no effect on SOD-1 in endothelial cells or adventitial fibroblasts. This SOD-1 increase was associated with an increase in sod1 gene expression, increase in SOD-1 activity, and decrease in O2(•-) levels. Lastly, to determine the role of SOD-1 in (•)NO-mediated inhibition of neointimal hyperplasia, we performed the femoral artery wire injury model in wild type and SOD-1 knockout (KO) mice, with and without (•)NO. Interestingly, (•)NO inhibited neointimal hyperplasia only in wild type mice, with no effect in SOD-1 KO mice. In conclusion, these data show the cell-specific modulation of O2(•-) by (•)NO through regulation of SOD-1 in the vasculature, highlighting its importance on the inhibition of neointimal hyperplasia. These results also shed light into the mechanism of (•)NO-dependent redox balance, and suggest a novel VSMC redox target to prevent neointimal hyperplasia.

Nitric oxide delivery via a permeable balloon catheter inhibits neointimal growth after arterial injury.

BACKGROUND: Neointimal hyperplasia limits the longevity of vascular interventions. Nitric oxide (NO) is well known to inhibit neointimal hyperplasia. However, delivery of NO to the vasculature is challenging. Our study aims to evaluate the efficacy of delivering NO to the site of injury using a permeable balloon catheter. Our hypothesis is that ultra-short duration NO delivery using a permeable balloon catheter will inhibit neointimal hyperplasia. MATERIALS AND METHODS: Ten-week-old male Sprague-Dawley rats underwent carotid artery balloon injury. Groups included: (1) control, (2) injury, (3) injury + periadventitial NO, and (4) injury + endoluminal NO via permeable balloon catheter. The catheter was inflated to 5 atm pressure for 5 min. Arteries were harvested 2 wk following injury. Morphometric assessment for neointimal hyperplasia and immunohistochemical staining for inflammatory markers were performed. RESULTS: Injury increased neointimal hyperplasia compared with control (intima/media area [I/M] ratio 1.07 versus 0.11, respectively, P < 0.001). Periadventitial delivery of NO reduced the I/M area ratio compared with injury alone (55% decrease, P < 0.001). Endoluminal delivery of NO also reduced the I/M area ratio compared with injury alone (65% decrease; P < 0.001). Both endoluminal and periadventitial NO affected the I/M ratio by reducing the intimal area (64% and 46%, respectively, P < 0.001) whereas neither affected the medial area. Periadventitial NO delivery increased lumen area (P < 0.05), whereas endoluminal NO delivery increased circumference (P < 0.05). Periadventitial NO delivery inhibited macrophage intimal infiltration compared with injury alone (P < 0.05). CONCLUSIONS: These data demonstrate that short-duration endoluminal NO delivery via permeable balloon catheters inhibits neointimal hyperplasia following arterial interventions. Endoluminal delivery of NO could become a focus for future clinical interventions.

Adventitial contributions of the extracellular signal-regulated kinase and Akt pathways to neointimal hyperplasia.

BACKGROUND: We recently reported that the efficacy of nitric oxide (NO) appears to be based on both sex and hormone status. The mechanism responsible for this differential efficacy is unknown. The aim of this study was to characterize the effect of sex, hormones, and NO on the extracellular signal-regulated kinase (ERK) and Akt signaling pathways after arterial injury. METHODS: Male and female Sprague-Dawley rats underwent castration or sham surgery. Two weeks later, they underwent carotid artery balloon injury. Treatment groups included the following: control, injury, and injury + 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO) (n = 5 per group). Arteries were harvested 2 weeks after injury and assessed for phospho-ERK (pERK) and phospho-Akt (pAkt) expression. RESULTS: After injury, more pERK and pAkt activity was seen in the adventitia than media in both sexes, regardless of hormone status (P < .05). In hormonally intact males, NO further increased pERK (44%) and pAkt (120%) after injury (P < .001). Castration attenuated the effects of NO. In hormonally intact females, NO caused the opposite pattern with pERK activity but did not affect pAkt activity. CONCLUSIONS: After arterial injury, ERK and Akt activity is significantly greater in the adventitia than the media, and depends on sex, hormone status, and NO. Understanding adventitial regulation of proliferative signaling pathways will allow the development of targeted therapies for neointimal hyperplasia.

Antioxidants modulate the antiproliferative effects of nitric oxide on vascular smooth muscle cells and adventitial fibroblasts by regulating oxidative stress.

BACKGROUND: S-nitrosothiols (SNO) release nitric oxide (NO) through interaction with ascorbic acid (AA). However, little is known about their combined effect in the vasculature. The aim of this study was to investigate the effect of AA on SNO-mediated NO release, proliferation, cell cycle progression, cell death, and oxidative stress in vascular cells. METHODS: Vascular smooth muscle cells and adventitial fibroblasts harvested from the aortae of Sprague-Dawley rats were treated with AA, ± S-nitrosoglutathione (GSNO), or ± diethylenetriamine NONOate (DETA/NO). NO release, proliferation, cell cycle progression, cell death, and oxidative stress were determined by the Griess reaction, [(3)H]-thymidine incorporation, flow cytometry, trypan blue exclusion, and 5-(and-6)chloromethyl-2',7'dichlorodihydrofluorescein staining, respectively. RESULTS: AA increased NO release from GSNO 3-fold (P < .001). GSNO and DETA/NO significantly decreased proliferation, but AA abrogated this effect (P < .05). Mirroring the proliferation data, changes in cell cycle progression induced by GSNO and DETA/NO were reversed by the addition of AA. GSNO- and DETA/NO-mediated increases in oxidative stress were significantly decreased by the addition of AA (P < .001). CONCLUSIONS: Despite causing increased NO release from GSNO, AA reduced the antiproliferative and cell cycle effects of GSNO and DETA/NO through the modulation of oxidative stress.

Insights into the effect of nitric oxide and its metabolites nitrite and nitrate at inhibiting neointimal hyperplasia.

OBJECTIVE: Periadventitial delivery of the nitric oxide (NO) donor PROLI/NO following arterial injury effectively inhibits neointimal hyperplasia. Given the short half-life of NO release from PROLI/NO, our goal was to determine if inhibition of neointimal hyperplasia by PROLI/NO was due to NO, or its metabolites nitrite and nitrate. METHODS AND RESULTS: In vitro, the NO donor DETA/NO inhibited proliferation of rat aortic vascular smooth muscle cells (RASMC), but neither nitrite nor nitrate did. In vivo, following rat carotid artery balloon injury or injury plus the molar equivalents of PROLI/NO, nitrite, or nitrate (n=8-11/group), PROLI/NO was found to provide superior inhibition of neointimal hyperplasia (82% inhibition of intimal area, and 44% inhibition of medial area, p<0.001). Only modest inhibition was noted with nitrite or nitrate (45% and 41% inhibition of intimal area, and 31% and 29% inhibition of medial area, respectively, p<0.001). No effects on blood pressure were noted with any treatment groups. In vivo, only PROLI/NO inhibited cellular proliferation and increased arterial lumen area compared to injury alone (p<0.001). However, all three treatments inhibited inflammation (p<0.001). CONCLUSIONS: PROLI/NO was more effective at inhibiting neointimal hyperplasia following arterial injury than nitrite or nitrate. However, modest inhibition of neointimal hyperplasia was observed with nitrite and nitrate, likely secondary to anti-inflammatory actions. In conclusion, we have demonstrated that the efficacy of NO donors is primarily due to NO production and not its metabolites, nitrite and nitrate.

The vascular adventitia: its role in the arterial injury response.

The belief that the adventitia serves only a structural purpose has changed over the last decade. Studies have begun to elucidate the role the adventitia plays in the arterial response to injury. The adventitial fibroblast plays an integral part in the development of neointimal hyperplasia. Adiponectin, an adipokine produced from periadventitial adipose tissue, exhibits numerous vasoprotective properties. Stem cells arise, in part, from the adventitia, and stem cell recruitment into the adventitia from the vasa vasorum has been shown to be important in the development of neointimal hyperplasia. The exact role the vasa vasorum plays in neointimal growth is poorly understood and different studies endorse conflicting viewpoints. Thus, understanding the nuances of adventitial pathophysiology will allow us to better appreciate the mechanisms behind the pathology of neointimal hyperplasia. This review will summarize recent findings on the active role the adventitia plays toward the development of neointimal hyperplasia.

Prevention of thromboembolic events in surgical patients through the creation and implementation of a computerized risk assessment program.

OBJECTIVES: Deep vein thrombosis (DVT) is a major source of postoperative morbidity and mortality and is currently a major quality improvement initiative. Mechanical and pharmacological prophylaxis is effective in preventing postoperative thromboembolic events, yet it remains underutilized in the clinical setting. Thus, the objective of this study was to develop and implement a computerized DVT risk assessment program in the electronic medical record and determine its effect on compliance with DVT prophylaxis guidelines. METHODS: A standardized DVT risk assessment program was developed and incorporated into the Computerized Patient Record System for all surgical patients at the Jesse Brown Veterans Affairs Medical Center. Four hundred consecutive surgical patients before and after implementation were evaluated for DVT risk, the prescription of pharmacological and mechanical DVT prophylaxis, and the development of thromboembolic events. RESULTS: With implementation of the DVT risk assessment program, the number of patients receiving the recommended pharmacological prophylaxis preoperatively more than doubled (14% to 36%) (P < .001), and use of sequential compression devices (SCD) increased 40% (P < .001). Overall, the percentage of at-risk patients receiving the recommended combined DVT prophylaxis of SCD and pharmacological prophylaxis increased nearly seven-fold (5% to 32%) (P < .001). The assessment also improved use of prophylaxis postoperatively, increasing SCD use by 27% (P < .001). With respect to DVT occurrence, there was an 80% decrease in the incidence of postoperative DVT at 30 days and a 36% decrease at 90 days; however, this did not reach statistical significance due to the low event rate. CONCLUSIONS: The creation and implementation of a standardized DVT risk assessment program in the electronic medical record significantly increased use of pharmacological and mechanical DVT prophylaxis before surgery in a Veterans Affairs Medical Center setting.