Visceral and renal artery aneurysms: a pictorial essay on endovascular therapy.

Visceral artery aneurysms (VAAs), which were once considered uncommon, are now being diagnosed with increasing frequency, a fact that reflects the routine use of computed tomography (CT), magnetic resonance imaging, and ultrasonography. Diagnostic radiology plays a major role in the detection and characterization of VAAs. Cross-sectional imaging can help exclude aneurysm rupture, which requires emergent treatment. CT angiography or catheter angiography can clearly depict the aneurysm and help identify other aortic, visceral, or peripheral aneurysms. Most important, radiologic examination can help determine the adequacy of the collateral blood supply to the vascular bed distal to the aneurysm, information that is essential prior to the initiation of endovascular treatment. Advances in endovascular therapy have allowed interventional radiologists to contribute to the management of VAAs. Coil embolization or covered stent placement can now be used to treat patients with aneurysms whose size or location would make a surgical approach problematic, as well as patients in whom surgery is considered to pose considerable risk.

Factors impacting functional health and resource utilization following abdominal aortic aneurysm repair by open and endovascular techniques.

We assessed the impact on patient outcomes of comorbidities and type of aneurysm repair, open vs. endovascular aortic repair (EVAR). Functional health status was measured prospectively using the Short Form 36 (SF-36) Health Survey. Length of stay (LOS) and need for postdischarge resources (nursing and rehabilitation) were compared between groups. We reviewed the records of 218 patients (126 open, 92 EVAR) who underwent intervention between 1998 and 2003. The SF-36 was completed preoperatively and at intervals ranging from 2 weeks to 1 year after intervention. To identify factors impacting outcome, univariate and multivariate analyses were performed. Overall mortality was 1.9%: 3.2% for open repair and 0% for EVAR (p = 0.13). Physical and mental health were higher during the 3 months following EVAR compared with open repair: physical function (PF) (65.2 +/- 4.1 vs. 54.0 +/- 4.1), vitality (VT) (55.5 +/- 2.5 vs. 44.9 +/- 3.4), and emotional role (ER) (74.9 +/- 5.0 vs. 51.4 +/- 6.7) (analysis of variance p < 0.05). Women following EVAR had decreased physical summary scores (PSS) (34.8 +/- 2.5 vs. 40.4 +/- 1.1, p < 0.05) compared with men postprocedure despite no difference preoperatively. Congestive heart failure (CHF) was an independent factor that negatively impacted PF, body pain (BP), and PSS. EVAR was associated with improved VT and ER. Differences among open repair and EVAR diminished over time. LOS (in days) was greater for open vs. EVAR (9.2 +/- 0.78 vs. 2.0 +/- 0.17) and in women following both open (11.8 +/- 1.5 vs. 8.0 +/- 0.9) and EVAR (3.2 +/- 0.9 vs. 1.8 +/- 0.1) procedures (p < 0.05). Factors that adversely affected LOS were open repair, age, renal insufficiency, pulmonary disease, CHF, and female gender. Following EVAR, patients were less likely to require home care or transfer to a rehabilitation facility than after open repair (14.1 vs. 36.0%, p < 0.05). Women were significantly more likely to require postdischarge care after open repair (48.7 vs. 30.1%) and EVAR (41.7 vs. 10.0%) (p < 0.05). Logistic regression identified female gender, open repair, advanced age, and pulmonary disease as independent predictors of need for postdischarge care. Those patients undergoing abdominal aortic aneurysm (AAA) repair by open technique (compared to EVAR) had significantly impaired functional health with regard to PF, VT, and ER in the first 3 months after surgery. CHF and hypertension also significantly impaired individual functional health scores. Of significance was that female gender was associated with increased LOS and increased utilization of postdischarge nursing and rehabilitation resources following both open and endovascular surgery for AAA.

Resolution of hemiballism after carotid endarterectomy: case report.

A 74-year-old man presented with a 3-week history of involuntary left-sided upper and lower extremity shaking without any focal neurologic deficit. Bilateral carotid artery duplex demonstrated severe stenosis of the right internal carotid artery and moderate stenosis of the left internal carotid artery. A right carotid endarterectomy was performed without complications and resulted in elimination of the left-sided involuntary movements postoperatively.

Resource utilization and outcomes: effect of transfer on patients with ruptured abdominal aortic aneurysms.

We evaluated the transfer of patients with the diagnosis of a ruptured AAA (rAAA) from community centers to a tertiary care center. Our purpose was to identify factors associated with mortality and outcomes following the open repair of rAAA and to evaluate the differences between transferred and nontransferred patients. All patients who underwent repair of rAAA at our institution between 1995 and 2002 were retrospectively reviewed. Univariate and multivariate analysis was performed to identify patient specific factors on presentation and intraoperatively. Fifty-two patients underwent repair of rAAA, 20 patients were transferred to our institution. The overall mortality rate was 67%. The mortality rates for nontransferred and transferred groups were 69% and 65%, respectively. The incidence of mortality within 24 hr of surgery was significantly higher in the patients who were not transferred, 10 vs. 41% (p < 0.05). Patient-specific factors assessed for impact on survival by logistic regression included decreased body temperature on arrival to our institution (p = 0.02) and free rupture (p = 0.05). Of intraoperative factors tested, low systolic blood pressure was significantly associated with mortality (p = 0.05). No difference in total length of stay was noted. Transfer patients' length of stay in the intensive care unit was significantly greater than that of nontransferred patients (18.8 +/- vs. 7.3 +/- days, p < 0.05). The difference in ICU cost was dollar 36,000 among groups. We found the acceptance of transfer patients from community centers with rAAA did not adversely affect patient survival. Transferred patients had an over twofold increases in ICU days used. The identification of hypothermia was the single independent factor associated with poor survival and may be a marker for transfer selection. Given reduced reimbursements and increased utilization, tertiary care centers will need to consider the economic ramifications of accepting transfer patients with rAAA.

Perirenal fixation as an independent factor in aortic remodeling after endovascular aortic aneurysm repair.

The purpose of our study was to evaluate the influence of perirenal fixation of endovascular aortic grafts on the rate of endoleak and aortic sac remodeling. Retrospective analysis of all patients (pts.) after undergoing endovascular aortic aneurysm repair (EVAR) at our institution was performed. Pre- and postoperative aortic dimensions were obtained from CT scans and angiograms. Intraoperative angiograms were reviewed and patients grouped by the proximity of the graft to the lowest renal arteries: group I: flush with the lowest renal artery; group II: < or = 5 mm distal to lowest renal artery; and group III: >5 mm distal to lowest renal artery. Of the 96 grafts placed between 2000 and 2002, 44 were AneuRx (Medtronic, Santa Rosa, CA) and 52 were Ancure (Guidant, Menlo Park, CA) devices. There were 39 pts. in group I, 42 in group II, and 11 in group III (data on 5 pts. were not obtained). At 6 months, the mean decrease in sac diameter for all groups was 0.42 +/- 0.08 cm (1: 0.56 +/- 0.11 cm; 11: 0.38 +/- 0.11 cm; III: 0.6 +/- 0.15 cm). There was no significant difference between each group. When perirenal fixation (group I) was compared with nonperirenal fixation (groups II and III), there was a significant difference in sac shrinkage at 6 months (p < 0.05, ANOVA). Group I had shorter necks and smaller aneurysms (2.2 +/- 0.1 cm and 5.3 +/- 0.1 cm) than those of groups II and III (2.7 +/- 0.1 cm and 5.7 +/- 0.1 cm, p < 0.05, ANOVA). There was no difference in aortic neck diameter or in aortic neck diameter to graft ratio. When controlled for the variables studied (AAA diameter, length of neck, diameter of neck, diameter of neck to graft ratio, and any endoleak by 6 months), logistic regression analysis identified perirenal fixation as the only significant factor in aortic sac shrinkage of >0.4 cm by 6 months (odds ratio = 16, p < 0.01). With the same variables, a linear regression model also identified perirenal fixation as the only predictive factor in aortic shrinkage (regression coefficient = 0.46, p < 0.05). The endoleak-free survival rate with perirenal fixation was 96 +/- 5% and without it was 80 +/- 7% (Kaplan Meier, p = 0.09, log rank). Perirenal placement of endovascular grafts is associated with a trend toward fewer endoleaks, and improved aortic sac shrinkage independent of aortic neck length, AAA diameter, diameter of neck, and endoleak. Failure to achieve perirenal placement of EVAG increased the likelihood of reduced or failed aortic sac shrinkage in this series.

Oral administration of L-arginine decreases necrosis of the epigastric skin flap in the rat.

BACKGROUND: We investigated the effect of prolonged oral arginine administration on tissue necrosis and perfusion in the rat skin flap. METHODS: Twenty-five Sprague-Dawley rats had an 8 x 8 - cm epigastric skin flap elevated and were divided in 2 groups, l-Arginine and Control, which respectively received oral 6% l-arginine solution or water for 8 days postoperatively. On postoperative day 8, area of flap necrosis was measured, and the animals were perfused systemically with 15-microm colored fluorescent microspheres before (blue) and after (yellow-green) ligation of the flap pedicle. RESULTS: l-Arginine reduced total flap necrosis (6.53 +/- 3.76 cm versus 11.91 +/- 4.12 cm; P < 0.01). After pedicle ligation, total flap perfusion remained unchanged in Control but diminished in the l-Arginine group (Control: 0.47 +/- 0.23 and 0.42 +/- 0.06; P = nonsignificant versus l-Arginine: 0.58 +/- 0.29 and 0.27 +/- 0.19; P < 0.01). Serum levels of l-arginine were higher in the l-arginine-treated animals (504 +/- 154 versus 152 +/- 34 micromol/l; P < 0.0001). CONCLUSIONS: Postoperative oral administration of l-arginine decreased flap necrosis in the rat epigastric skin flap. Flap perfusion following oral l-arginine was more dependent on the main vascular pedicle.

The effect of single administration of vascular endothelial growth factor or L-arginine on necrosis and vasculature of the epigastric flap in the rat model.

OBJECTIVES: Vascular endothelial growth factor (VEGF) and nitric oxide (NO) produce vasodilation, induce angiogenesis, and improve survival of surgical flaps. We used the rat epigastric skin flap to study the effect of a single intra-arterial dose of VEGF or L-arginine, a substrate for NO production, on flap regional necrosis and pedicle dependence of flap perfusion. METHODS: In 30 Sprague-Dawley rats an 8 x 8 cm2 skin flap, consisting of four vertical zones marked A through D (right to left), based on the proximal right inferior epigastric vessels was raised. Subsequently, 1 ml of either saline (control, n =10), 5 microg VEGF (VEGF, n = 10), or 50 mg of L-arginine (L-arginine, n = 10) was injected into the arterial pedicle by cannulating the right saphenous artery, and the flap was resutured in place. After 8 days, the animals were perfused systemically with 15 microm coloured fluorescent microspheres before (blue) and after (yellow-green) ligation of the right inferior epigastric vascular pedicle. After sacrifice, the area of flap necrosis was measured in each zone by templates and weight-to-surface ratio, and the flap zones were harvested and processed for determination of fluorescence and blood flow. RESULTS: Administration of VEGF or L-arginine resulted in decreased total and regional (zone D) flap necrosis (ANOVA <0.001). The total and regional flap shrinkage was greater in the experimental groups (ANOVA <0.02). While VEGF and L-arginine decreased the percentage of necrosis in the zone most distal to the pedicle (ANOVA <0.01) only L-arginine diminished percentage of total flap necrosis (p = 0.04). In the VEGF group, total and regional flap perfusion did not change after pedicle ligation, but perfusion decreased significantly in zones B through D in the L-arginine treated rats. CONCLUSION: Single intra-pedicle administration of VEGF or L-arginine decreased necrosis of the epigastric skin flap at 8 days postoperatively, but flap shrinkage also increased in the zone with the greatest degree of necrosis. Perfusion data suggest that beneficial effects of VEGF and L-arginine on flap survival may be based on different mechanisms.

Influence of endovascular training on fellowship and general surgical training.

PURPOSE: As endovascular procedures develop, there is a risk of diminished training of residents and fellows in traditional open surgery. We evaluated the effect of our endovascular program, initiated in 1999 coincident with the Federal Drug Administration's approval of endoluminal vascular aortic grafts, on the number of endovascular procedures and open abdominal aortic aneurysm (AAA) repairs performed in comparison to national trends. METHODS: The experience of vascular fellows and chief residents at completion of training (1996-2002) was reviewed and compared with the national mean case numbers before and after initiation of our endovascular program. RESULTS: The development of an endovascular program increased the total number of aneurysms repaired at the Robert Wood Johnson (RWJ) Medical School from 49 +/- 15 to 92 +/- 8 per year (P < 0.01). The number of vascular operations performed by the RWJ fellow increased from 320 +/- 48 to 553 +/- 155 per year (P < 0.05). The number of operations performed nationally by vascular fellows also increased during the same period, but did not reach statistical significance. There was no change in the number of open AAA repairs performed by the RWJ fellow or nationally. There was also no change in the average number of vascular operations completed by RWJ chief residents or nationally (160 +/- 17 versus 157 +/- 1 and 192 +/- 4 versus 189 +/- 4, respectively; P > 0.05). However, the average number of open AAA repairs performed nationally by general surgical chief residents decreased from 10 +/- 0.3 to 9 +/- 0.4 (P < 0.05). CONCLUSION: An endovascular program can increase the total number of AAA repairs performed without influencing the total number of vascular operations performed by general surgical chief residents. There was a decrease in open AAA repairs performed nationally by general surgical chief residents. The advancement of endovascular therapies may decrease the number of open procedures available for trainees in both general and vascular surgery. Perhaps those that will specialize in the field of vascular surgery should have the benefit of those open procedures.

Overexpression of endothelial nitric oxide synthase increases skeletal muscle blood flow and oxygenation in severe rat hind limb ischemia.

OBJECTIVE: Although nitric oxide (NO) has a critical role in angiogenesis, the therapeutic potential of NO synthase overexpression in severe ischemia remains undefined. We tested the hypothesis that overexpression of endothelial NO synthase (eNOS) would improve tissue perfusion in severe hind limb ischemia. METHODS: Severe hind limb ischemia was induced in 122 adult male Sprague-Dawley rats. Ten days after the induction of hind limb ischemia, vascular isolation and intraarterial delivery of an adenoviral vector encoding eNOS (AdeNOS), a control adenoviral vector (AdE1), or phosphate-buffered saline solution (PBS) was performed. Skeletal muscle blood flow, muscle oxygen tension, angiography, and immunohistochemistry for capillary counts were measured. RESULTS: Gene transfer of AdeNOS increased eNOS protein expression and enzyme activity. Two weeks after gene transfer, skeletal muscle blood flow was fourfold higher in eNOS-transduced than in AdE1-transduced or PBS treated rats and was similar to exercise-induced maximal flow in nonischemic muscle. eNOS overexpression increased muscle oxygen tension in a titer-dependent fashion. This increase persisted 1 month after transduction, even though eNOS enzyme activity had declined to normal levels. Angiography and capillary counts showed that eNOS overexpression increased the size and number of collateral arteries, but did not significantly increase the capillary-muscle fiber ratio. CONCLUSIONS: eNOS overexpression in an ischemic rat hind limb significantly increased skeletal muscle blood flow, muscle oxygen tension, and collateral arteries (arteriogenesis). Furthermore, eNOS overexpression did not result in capillary angiogenesis above control levels. These studies demonstrate the potential for eNOS overexpression as treatment for severe limb ischemia in human beings.

Emergent surgery for massive pulmonary embolism on the basis of clinical diagnosis.

We treated a 52-year-old man for a large pleural effusion that had occurred after he fell from a ladder. Upon discharge from the hospital, the patient collapsed and was nonresponsive and hypotensive. We suspected the cause to be pulmonary embolism. When it became evident that this patient would die without emergent intervention, he was taken to surgery. A massive clot was removed from the left pulmonary artery, and multiple smaller clots were removed from both pulmonary arteries. The patient recovered and was discharged from the hospital on the 11th postoperative day. To our knowledge, this is the 1st report of pulmonary embolectomy being performed on the basis of clinical diagnosis alone.

Multiple isolated aneurysms in a case of "burned out" Takayasu aortitis.

Takayasu aortitis (TA) is a chronic inflammatory disease predominantly seen in young Asian women. The disease is idiopathic and largely affects the aorta and its major branches. The basic pathologic changes in TA are fibrosis and subsequent occlusion of the large arteries. TA is classically termed "pulseless" disease, with manifestations during the occlusive stage including limb ischemia, renovascular hypertension, and heart failure. Arterial dilation and aneurysm are largely unappreciated manifestations of TA, but they occur in as many as 32% of affected patients. We report chronic "burned out" TA in a 23-year-old Hispanic woman with isolated aneurysms of the descending thoracic aorta, abdominal aorta, and common iliac arteries, without occlusive disease.

Adeno-associated viral vector-mediated gene transfer of VEGF normalizes skeletal muscle oxygen tension and induces arteriogenesis in ischemic rat hindlimb.

Critical limb ischemia is an important clinical problem that often leads to disability and limb loss. Vascular endothelial growth factor (VEGF), delivered either as recombinant protein or as gene therapy, has been shown to promote both collateral artery formation (arteriogenesis) and capillary angiogenesis in animal models of hindlimb ischemia. However, none of the previous studies has demonstrated an improvement in tissue hypoxia, the condition that drives the molecular response to ischemia. Furthermore, the optimal vector and route of gene delivery have not been determined. Recently, adeno-associated viral (AAV) vectors, which efficiently transduce skeletal muscle and produce sustained transgene expression, have been used as gene therapy vectors. We asked whether an intra-arterial injection of AAV-VEGF(165) normalizes muscle oxygen tension by increasing skeletal muscle oxygen tension, and promotes arteriogenesis and angiogenesis in a rat model of severe hindlimb ischemia. We found that AAV-VEGF treatment normalized muscle oxygen tension in the ischemic limb. In contrast, vehicle and AAV-lacZ-treated limbs remained ischemic. Collateral arteries were more numerous in AAV-VEGF-treated rats, but, surprisingly, capillaries were not. We conclude that intra-arterial AAV-mediated gene transfer of AAV-VEGF(165) normalizes muscle oxygen tension and leads to arteriogenesis in rats with severe hindlimb ischemia.

Effect of adenoviral titer and instillation pressure on gene transfer efficiency to arterial and venous grafts ex-vivo.

OBJECTIVE: Adenoviral-mediated gene transfer to arterial and venous grafts has potential in the treatment of a number of vascular diseases. Despite widespread use of these vectors to mediate gene transfer to blood vessel walls, the optimal transduction conditions for each type of vessel has yet to be determined. Our objective was to study the effect of adenoviral titer and instillation pressure on efficiency of gene transfer to arterial and venous grafts ex-vivo. METHODS: Jugular vein and carotid artery segments of 8 cm were harvested from Yorkshire Cross pigs. Tissue culture media or different titers of an adenoviral vector encoding human placental alkaline phosphatase (hpAP) were instilled into venous and arterial grafts at 0 mm Hg or 80 to 100 mm Hg of pressure and bathed externally in the same solution at 37 degrees C for 30 minutes. The grafts were rinsed, opened longitudinally, and incubated in culture media at 37 degrees C for 48 hours. Grafts were fixed and stained for hpAP transgene expression to quantitate percent luminal transduction or homogenized for alkaline phosphatase (AP) activity to determine total transmural transduction. RESULTS: For venous grafts, the percent luminal area stained for hpAP was greatest with 10(8) plaque-forming units/mL at 0 mm Hg (81% +/- 7%) and decreased with increasing titers (53% +/- 9% at 10(9) pfu/mL and 44% +/- 11% at 5 x 10(9) pfu/mL; n = 7; P <.05). No increase in percent luminal area stain was achieved with an instillation pressure of 80 to 100 mm Hg at any viral titer. The inverse finding was observed in arterial grafts. For arterial grafts, the greatest percent luminal area stained was achieved with 5 x 10(9) pfu/mL at 80 to 100 mm Hg (76% +/- 7%). An instillation pressure of 80 to 100 mm Hg increased the percent luminal area stained at 10(8) pfu/mL from 31% +/- 9% to 66% +/- 8% (n = 8; P =.01). For venous grafts, total AP activity peaked with 10(9) pfu/mL at 0 mm Hg and decreased with an instillation pressure of 80 to 100 mm Hg (30.6 +/- 9.7 U/mg versus 10.9 +/- 2.5 U/mg; n = 7; P <.01). However, for arterial grafts, total AP activity peaked with 5 x 10(9) pfu/mL (0 mm Hg) and increased with an instillation pressure of 80 to 100 mm Hg (32.8 +/- 9.9 U/mg versus 63.4 +/- 20.5 U/mg; n = 8; P <.05). CONCLUSION: High transduction efficiency can be achieved with adenoviral-mediated gene transfer of arterial and venous grafts. Gene transfer with the vascular graft's physiologic pressure conditions improved transduction efficiency for the artery (80 to 100 mm Hg) and vein (0 mm Hg). Comprehensive analysis of adenoviral transduction conditions is important to realize the full promise of adenoviral-mediated gene transfer.

Correlation of a simple direct measurement of muscle pO(2) to a clinical ischemia index and histology in a rat model of chronic severe hindlimb ischemia.

PURPOSE: The lack of suitable experimental models of chronic severe limb ischemia and deficiencies in the available methods that allow for direct intermittent measurement of regional limb perfusion are obstacles to the evaluation of recently developed molecular strategies to reverse severe limb ischemia. Our aim was to develop a model of clinically relevant severe limb ischemia and correlate a simple direct measurement of muscle pO(2) to a clinical ischemia index, muscle mass, and capillary density. METHODS: Severe hindlimb ischemia was induced in 44 adult rats with ligation of the left common iliac artery, the femoral artery, and their branches. The effect of ischemia on muscle pO(2) was measured in the left gastrocnemius with room air and with 100% oxygen at 3, 10, 24, and 40 days after ischemia was induced. Clinical ischemia index, muscle mass, cellular proliferation, and capillary density also were assessed. RESULTS: The clinical ischemia index of the left limb was most severe at day 10, with evidence of pressure sores, a pale and dusky limb, and abnormal gait. With the rats breathing room air, muscle pO(2) was significantly lower in the left limbs than in the right limbs at days 3, 10, 24, and 40. After an oxygen challenge (100% O(2)), muscle pO(2) was significantly lower at 3, 10, and 40 days. At 3 days, the fraction of muscle mass per total body weight of the left tibialis anterior (TA) was significantly greater than the right TA as a result of edema and inflammation. By days 10, 24, and 40, the left gastrocnemius and TA masses were significantly less than the right as a result of muscle atrophy. Histopathology showed severe necrosis in the left gastrocnemius and TA on day 3. Inflammation was greatest by day 10. Necrotic muscle regenerated but remained atrophic at 40 days. The TA was slower to recover than the gastrocnemius. Capillary densities and capillary-to-muscle fiber ratios were greater in the ischemic limb than in the normal limb at day 24. Cellular proliferation as determined with bromodeoxyuridine labeling reagent staining was maximal in the ischemic limb at day 3. CONCLUSION: We have developed a rat model of chronic severe hindlimb ischemia with persistent ischemia as shown with a simple direct measurement of muscle pO(2) for up to 40 days. This model of severe hindlimb ischemia may be applicable for future studies of molecular strategies to treat severe limb ischemia in humans.

Therapeutic angiogenesis for critical limb ischemia: invited commentary.

Lower extremity arterial occlusive disease results in tissue ischemia of the legs and is relatively common in the elderly. Clinically, it may be asymptomatic, cause muscle pain during exercise, or progress to a severe degree of ischemia that may result in limb loss. Although bypass surgery and angioplasty have increased the rate of limb salvage in these patients, amputation of the affected limb remains a common outcome for many patients. Therapeutic angiogenesis is the administration of angiogenic factors, or genes encoding these factors, to promote neovascularization and thereby increase blood flow to the ischemic leg. We have developed an animal model of hindlimb ischemia in which to study therapeutic angiogenesis. We chose nitric oxide as the angiogenic factor for our experiments because of its ability to induce angiogenesis, vasodilation, and inhibit inflammation. In this review, we will discuss our experience with our model of hindlimb ischemia, as well as discuss our results of gene therapy for therapeutic angiogenesis using nitric oxide.