Aortouni-iliac endografting as an alternative salvage procedure to open conversion in failed endovascular aneurysm repair.

PURPOSE: To present a single-center experience with failed EVAR requiring conversions comparing open surgery to a minimally invasive procedure modifying the existing stent-graft into an aortouni-iliac (AUI) configuration. METHODS: A prospectively maintained database at our tertiary care university hospital was interrogated to identify all patients with failed EVAR who had undergone either stent-graft modification into an AUI configuration or open conversion between March 1995 and January 2012. Patients with late aneurysm ruptures were excluded. The search found 30 patients (one had initial treatment elsewhere) who required conversion among the 688 patients who had undergone EVAR in that time period. Before conversion, 16 (53%) patients had prior endovascular corrections to maintain aneurysm exclusion. RESULTS: An average time of 52.2 months (median 46.9, IQR 0.0-92.5) elapsed between initial EVAR and conversion. There were 11 early conversions (including 7 on-table), while 19 procedures were done >30 days post EVAR. Twenty-two (73%) patients underwent AUI endografting, while open conversions were carried out in 8 (27%). Mean hospital stay after conversion was 19.5 days (median 13.0, IQR 8.0-17.0). Overall mortality after conversion was 3.3% (1 patient after on-table open conversion), but since the introduction of AUI endografting as an alternative treatment approach, 30-day mortality following conversions fell to zero. CONCLUSION: Modification of a failed stent-graft into an AUI configuration serves as a less invasive treatment option compared to open conversion and allows salvage of the failed device. With the implementation of this alternative approach, mortality after conversion parallels the mortality of elective abdominal aneurysm repair.

Endovascular treatment of delayed rupture following prior abdominal aortic aneurysm repair achieves better survival rates.

PURPOSE: To test the hypothesis that endovascular treatment of delayed aneurysm rupture achieves significantly better survival rates compared to surgical conversion. METHODS: All patients sustaining delayed rupture following prior exclusion of an abdominal aortic aneurysm (AAA) either by endovascular aneurysm repair (EVAR) or open graft replacement from March 1995 through December 2011 were retrieved from a prospectively maintained database at a tertiary care university hospital. During the study period, 35 patients (32 men; mean age 72.9 years) presented with delayed rupture at a median 2.4 years (interquartile range 1.3-4.3) after initial AAA repair by EVAR (n=22) or open surgery (n=13). Causes of post-EVAR rupture were graft-related endoleaks, while ruptures after open repair occurred at anastomotic suture sites. Patients were divided into groups regarding type of treatment for delayed rupture: 20/35 (57%) underwent successful EVAR (10 redo procedures), 13/35 (37%) had surgery (3 redo procedures), and 2/35 (6%) patients received comfort care only. The primary endpoint was 30-day mortality. RESULTS: The 30-day mortality after curative treatment was 25% (5/20) for endovascular treatment compared to 54% (7/13) for surgery (p=0.14). Including additional deaths beyond 30 days, the overall in-hospital mortality was 52% (17/33). The Kaplan-Meier survival estimate for patients undergoing endovascular treatment was significantly higher (p=0.011). CONCLUSION: Endovascular treatment of delayed rupture is feasible and helps to reduce mortality. Our data suggest that endovascular procedures are a superior treatment option for EVAR-suitable patients with delayed rupture compared with surgical conversion.

Repair of abdominal aortic aneurysms: the benefits of offering both endovascular and open surgical techniques.

Two treatment options are available for abdominal aortic aneurysms (AAAs): open surgical technique with graft replacement and endovascular aortic aneurysm repair (EVAR) as a minimally invasive procedure. The intention of this review is to highlight the advantages of both procedures and to demonstrate that offering both procedures is beneficial for the patient when he or she makes the important decision regarding which treatment to select. A comparative evaluation of both treatment options is offered as well as a short description of the risk of rupture and its consequences. The authors discuss the latest literature as well as their own experiences. An innovative statistical approach-the propensity score-based Cox model-is presented to evaluate the 2 treatment options. The benefits of offering both EVAR and open surgery permit optimal management of AAA for the individual patient and tailor the treatment to his or her organ dysfunctions and impaired physical status. In addition, EVAR offers a treatment option for otherwise incurable high-risk patients.

Endovascular stent grafting versus open surgical operation in patients with infrarenal aortic aneurysms: a propensity score-adjusted analysis.

BACKGROUND: Although transfemoral endovascular aneurysm management (TEAM) of infrarenal abdominal aortic aneurysms (AAA) is widely performed, open graft replacement is still considered the standard of care. The aim of this study was to investigate whether clear indications for TEAM can be established in patients with significant comorbidities without investigating differences in relative procedure efficacy or durability. METHODS AND RESULTS: A propensity score-based analysis of 454 consecutive patients treated electively for AAA from January 1995 through December 2000 was performed. Of those 454 patients, 248 received open surgery and 206 received TEAM. In-hospital mortality rates (MRs) were compared. After adjusting for propensity scores, a Cox proportional hazard model (COX) was employed to test the influence of the respective treatment on postoperative 900-day survival estimates (SEs). Several potential preoperative risk factors were used as covariates. The MR of all patients was 3.7%. Explorative analysis demonstrated that patients treated by TEAM presented with significantly more risk factors. In American Society of Anesthesiologists class IV patients, a significant difference in MR was detected (4.7% for TEAM versus 19.2% for open surgery; P<0.02). After adjusting for the propensity to receive TEAM or open surgery, a regression analysis of survival based on COX revealed predictive influences of impaired kidney (P<0.047) or pulmonary function (P<0.001), increased age (P<0.05), and selection of treatment modality (P<0.002) on SE. CONCLUSIONS: TEAM represents a less invasive procedure for AAA therapy in patients with significant preoperative risk factors. Especially in geriatric patients with multiple morbidities, TEAM offers a method of therapy with acceptable MRs and SEs, making active treatment possible in otherwise incurable patients.

Abdominal aortic aneurysms and concomitant diseases requiring surgical intervention: simultaneous operation vs staged treatment using endoluminal stent grafting.

HYPOTHESIS: To investigate whether staged or synchronous treatment of infrarenal abdominal aortic aneurysms (AAAs) and concomitant diseases (CDs) requiring surgical repair plays a clinical role. We considered endovascular aneurysm repair (EVAR) in particular. DESIGN: Review of a prospectively gathered database. SETTING: Tertiary care university teaching hospital. PATIENTS: We reviewed a total of 946 patients receiving elective AAA exclusion from 1980 through 2002. We divided the period into 2 observation intervals: 1980-1994, when only open graft replacement was available (n = 331), and 1995-2002, with 615 patients (326 who had open graft replacement and 289 who had EVAR). With regard to the physical status, expressed by the score from the American Society of Anesthesiologists (Park Ridge, Ill), we recorded in-hospital mortality rates and checked possible differences. MAIN OUTCOME MEASURES: Indications for therapy and mortality rates before and after the availability of EVAR. RESULTS: During the first interval, 14 simultaneous operations were carried out. During the second period, 19 patients received simultaneous operations while 49 underwent staged treatment using EVAR. The overall mortality rate was 3.7%. Irrespective of the American Society of Anesthesiologists classification, the mortality rate for patients who had EVAR was 0% in comparison with 13.6% for patients in American Society of Anesthesiologists class 3 or 4 after open graft replacement (P<.03). CONCLUSIONS: The coincidence of a patient having both an AAA and a CD is rare but should not be neglected. Staged treatment of AAAs using EVAR followed by surgical therapy for CDs can be an effective causal therapy with an acceptable mortality rate provided that suitable aneurysm anatomy exists.

CpG oligonucleotides elicit antitumor responses in a human melanoma NOD/SCID xenotransplantation model.

For patients with advanced malignant melanoma, the 5 y survival rate with current treatment modalities is low. There is an urgent need for more effective therapeutic concepts. One approach with great potential is to stimulate the body's own immune defense to reject cancer cells using CpG oligonucleotides. Distinct oligonucleotides containing nonmethylated cytidine residues in cytidine-guanosine dinucleotides with particular flanking bases (CpG motifs) are capable of eliciting powerful immune stimulation by mimicking infectious disease. We evaluated the in vivo antitumoral effects of CpG oligonucleotides against human malignant melanoma xenografts in NOD/SCID mice. CpG oligonucleotides administered in single peritumoral subcutaneous injections three times per week resulted in elevated plasma levels of interleukin-12 and significant inhibition of the growth of established tumor xenografts by 60% (p<0.016) compared to the saline control. In addition to this a significant invasion of macrophages into tumor xenografts and increased numbers of Langerhans-cell-derived dendritic cells in draining lymph nodes could be observed. Our findings demonstrate the antitumor activity of oligonucleotides containing immune-stimulatory CpG motifs in a xenotransplantation model with absent B, T cells and a lack of natural killer cell function.

Mcl-1 antisense therapy chemosensitizes human melanoma in a SCID mouse xenotransplantation model.

It is well established that high expression of the antiapoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL can significantly contribute to chemoresistance in a number of human malignancies. Much less is known about the role the more recently described Bcl-2 family member Mcl-1 might play in tumor biology and resistance to chemotherapy. Using an antisense strategy, we here address this issue in melanoma, a paradigm of a treatment-resistant malignancy. After in vitro proof of principle supporting an antisense mechanism of action with specific reduction of Mcl-1 protein as a consequence of nuclear uptake of the Mcl-1 antisense oligonucleotides employed, antisense and universal control oligonucleotides were administered systemically in combination with dacarbazine in a human melanoma SCID mouse xenotransplantation model. Dacarbazine, available now for more than three decades, still remains the most active single agent for treatment of advanced melanoma. Mcl-1 antisense oligonucleotides specifically reduced target protein expression as well as the apoptotic threshold of melanoma xenotransplants. Combined Mcl-1 antisense oligonucleotide plus dacarbazine treatment resulted in enhanced tumor cell apoptosis and led to a significantly reduced mean tumor weight (mean 0.16 g, 95% confidence interval 0.08-0.26) compared to the tumor weight in universal control oligonucleotide plus dacarbazine treated animals (mean 0.35 g, 95% confidence interval 0.2-0.44) or saline plus dacarbazine treated animals (mean 0.39 g, 95% confidence interval 0.25-0.53). We thus show that Mcl-1 is an important factor contributing to the chemoresistance of human melanoma in vivo. Antisense therapy against the Mcl-1 gene product, possibly in combination with antisense strategies targeting other antiapoptotic Bcl-2 family members, appears to be a rational and promising approach to help overcome treatment resistance of malignant melanoma.

Aortic mural thrombi in patients with inflammatory bowel disease: report of two cases and review of the literature.

Thromboembolic events are a known complication in inflammatory bowel disease (IBD). We report on 2 young women with IBD and aortic mural thrombi as a source of arterioarterial embolization to the lower limbs resulting in significant morbidity. The first case was a 36-year-old woman with severe ulcerative colitis who presented with signs of microembolism into two toes of her right foot. A thrombus in the otherwise normal infrarenal aorta with occlusion of the inferior mesenteric artery was revealed by computed tomography (CT) and intrarterial angiography. The digital ischemia resolved without sequelae. The second case was a 41-year-old woman with Crohn's disease complicated by fistulas. She developed acute ischemia of her right leg. Arteriography and CT revealed infrapopliteal embolic occlusions and a thrombus in the distal otherwise normal abdominal aorta and the left iliac artery. A primarily successful thrombectomy had to be repeated 5 times because of reocclusion. Eventually the leg was exarticulated at the knee. In both patients no further thromboembolic event occurred during follow-up of 4 1/2 years and 5 1/2 years, respectively, and aortic thrombi had resolved at follow-up CT scans. Extensive work up for hypercoagulability was negative in both patients. We consider IBD as the most likely trigger for arterioarterial embolization in the absence of thrombophilia in both patients. Finally we give an overview of the literature of similar cases with aortic mural thrombi in IBD patients.

Ischemia/reperfusion injury of skeletal muscle: plasma taurine as a measure of tissue damage.

BACKGROUND: Cell membrane rupture by oxygen-derived free radicals is a systematic feature of ischemia/reperfusion (I/R) injury. High taurine concentration gradients in skeletal muscle prompted us to evaluate whether plasma taurine levels (pTau) are a useful marker of I/R injury after different periods of ischemia. METHODS: Rabbits were randomly assigned to either 1 or 2.5 hours of hind-limb ischemia followed by 2 hours of reperfusion (groups IR1 [n = 12] and IR2.5 [n = 13], respectively). Corresponding sham groups (SHAM1 [n = 8] and SHAM2.5 [n = 9]) were used as controls. Analyzed parameters included histomorphometry and electron microscopy of skeletal muscle biopsies, pTau, and plasma level of malondialdehyde. Skeletal muscle function was assessed 3 weeks after I/R injury. RESULTS: No significant morphologic changes were detectable at the end of ischemia. After reperfusion, mild interstitial edema with intact muscle cell membranes developed in IR1 group; pTau was not increased. IR2.5 group, by contrast, showed severe interstitial edema formation (interfiber area increased by 112%, P <.005), microvascular constriction (microvessel area decreased by 33%, P <.0005), and damage to the muscle cell membranes that was confirmed by the increased plasma malondialdehyde. pTau was higher than in the SHAM2.5 group (P <.0005). Pronounced cell damage in IR2.5 group resulted in impaired muscle function (maximal tetanic tension was reduced 2 times, P <.005) but not in IR1 group. CONCLUSION: Skeletal muscle tolerates 1 h/2 h but not 2.5 h/2 h of I/R, the latter resulting in interstitial edema formation, microvascular constriction, and a late muscle dysfunction. Cell membrane rupture through stimulated lipid peroxidation promotes leakage of intracellular taurine, leading to increased pTau after reperfusion and may be considered as prognostically unfavorable in terms of organ function reversibility. In the rabbit model, pTau seems to be a sensitive marker of I/R injury to skeletal muscle.

Collagen- versus gelatine-coated Dacron versus stretch PTFE bifurcation grafts for aortoiliac occlusive disease: long-term results of a prospective, randomized multicenter trial.

BACKGROUND: In this prospective randomized multicenter trial, knitted gelatine-coated Dacron, knitted collagen-coated Dacron, and stretch polytetrafluoroethylene (PTFE) aortic bifurcation grafts were compared for their long-term results. METHODS: Between 1991 and 1998, 149 patients undergoing elective revascularization for aortoiliac occlusive disease were prospectively randomized at 3 tertiary referral centers of vascular surgery. The patients received either gelatine-coated Dacron (GEL-D) grafts (n = 52), collagen-coated Dacron (COL-D) grafts (n = 49), or stretch PTFE grafts (n = 48). RESULTS: No intraoperative deaths were recorded. The 30-day mortality was 4%. The mean follow-up time was 97 months. Primary patency rates were 77% for GEL-D, 78% for COL-D, and 79% for PTFE at 8 years. The differences were not different (P >.8). Secondary corrected 8-year patency rates were also not significantly different (P >.5): 91% for GEL-D, 96% for COL-Dm and 90% for PTFE. Five Dacron and 1 PTFE grafts were affected by infections. CONCLUSIONS: Bifurcation grafts for revascularization of aortoiliac occlusive disease using these 3 materials were comparable in terms of primary and secondary patency and long-term complication rates.

Carotid resection and reconstruction for locally advanced head and neck tumors.

Head and neck surgeons hesitate to resect the carotid artery because of the postoperative risk of neurologic sequelae. However, there is no curative therapeutic option for head and neck neoplasms involving the carotid artery, with the exception of complete tumor removal. To evaluate the benefits and risks of carotid revascularization techniques in locally advanced head and neck tumors we performed a retrospective analysis in an institutional, tertiary care medical center. Seven patients (5 males, 2 females) with a median age of 58 years underwent en bloc removal of locally advanced head and neck tumors, including carotid resection and revascularization, in the University of Vienna General Hospital, over a 15-year period. In six patients carotid reconstruction was accomplished by bypass grafting (five autologous grafts, one synthetic graft) and in one patient angiopatchplasty was used. There were no perioperative neurologic complications or deaths. Survival was > 12 months in 5/7 patients; the other 2 patients died within 6 months due to untractable progression of cancer. We conclude that carotid revascularization techniques offer the possibility of better local control for advanced head and neck tumors without additional risks of neuromorbidity or mortality.

[Ruptured abdominal aortic aneurysms: status quo after a quarter century of treatment experience]. / Rupturierte abdominelle Aortenaneurysmen: Status quo nach einem Vierteljahrhundert Behandlungserfahrung.

BACKGROUND: Postoperative mortality rates between 40% and 50% have been invariably reported for the treatment of ruptured abdominal aortic aneurysms (rAAA) over the last 50 years. The aim of this analysis was to investigate which patient subgroups benefit from open surgery and in which subgroups a change of treatment strategies should be considered due to lack of improvement despite optimal patient management. PATIENTS AND METHODS: From 1980 to 2002 a total of 230 patients underwent surgery because of a ruptured AAA. The observation period was divided into 3 intervals to achieve an approximately equal distribution of patients. The effect of the observation period and of baseline parameters on mortality rates were investigated. RESULTS: Between 1980 and 1990, 72 patients were operated with a mortality rate of 38.9% (n = 28). During the second period (1991-1996) surgery was performed in 72 patients with a mortality rate of 40.3% (n = 29). In the third observation interval (1997-2002) 86 patients underwent surgery with an unvaried high mortality rate of 40.7% (n = 35). By applying a logistic regression model including age, gender, modality of rupture, location of cross-clamping and type of operation, only the modality of rupture and the patient's age, which are uncontrollable by the surgeon, could be shown to have a significant impact. CONCLUSION: Summing up these findings, open surgical repair of rAAA only leads to acceptable results when performed in younger patients without supposed comorbidities. Survival appears to be accidental in patients with advanced age and increased prevalence of relevant comorbidities/underlying diseases. Minimally invasive techniques may offer promising treatment options to those patients, as they do in elective interventions.

Secondary modification into aortouniiliac configuration to salvage failed endovascular aneurysm repair is safe and effective but not associated with higher intervention rates during long-term follow-up.

BACKGROUND: Reports of secondary modifications into aortouniiliac configuration to salvage-failed endovascular aneurysm repair (EVAR) are limited. We evaluated long-term results after these procedures and compared them with those after primary aortouniiliac endografting (AUE). METHODS: A retrospective review of all EVAR performed from March 1995 until July 2011 was conducted. Patients were included when primary AUE (group I) or modification into aortouniiliac configuration (group II) was done. RESULTS: Data analysis obtained 27 group I and 23 group II patients. Salvage of failed EVAR could be achieved in 96% of group II patients, and mortality was zero. Frequency of adverse events and amount of interventions to maintain aneurysm exclusion were not increased after secondary AUE. Kaplan-Meier estimates for long-term survival between groups were comparable (P = .36). CONCLUSIONS: Secondary AUE allows correction of graft-related endoleaks potentially leading to late aneurysm rupture. Complications and adverse events throughout long-term follow-up were not necessarily increased when compared with primary AUE.

Improved survival after abdominal aortic aneurysm rupture by offering both open and endovascular repair.

BACKGROUND: In the treatment of ruptured abdominal aortic aneurysm (rAAA), the results of open graft replacement (OGR) have remained constant but discouraging for the last 4 decades. Provided suitable anatomy, elective endovascular abdominal aortic aneurysm repair (EVAR) is less invasive and leads to improved perioperative mortality. Thus, it is reasonable to assume that endovascular treatment should improve the results of rAAA therapy. OBJECTIVE: To determine whether the use of both endovascular and open repair of rAAA leads to improved results. DESIGN: A single-center, retrospective analysis of 89 patients suffering from rAAA treated either by EVAR or OGR. PATIENTS: From October 1999 until July 2006, a consecutive series of patients with rAAA were analyzed. Time was divided into 2 periods of 41 months. During the first period, 42 patients were treated by OGR exclusively. Period 2 started with the availability of an EVAR protocol to treat rAAA; 31 patients received open repair while 16 patients underwent EVAR. MAIN OUTCOME MEASURES: Kaplan-Meier survival estimates were calculated and compared. RESULTS: Survival estimates showed a statistically significant reduction in overall postoperative mortality following the introduction of EVAR (P < .03). The 90-day overall mortality rate was reduced from 54.8% to 27.7% during the second period (P < .01). Survival of patients older than 75.5 years was especially improved (75% vs 28.6%; P < .01). There was a parallel pattern of significant reduction of the mortality rate after OGR to 29% (P < .03). CONCLUSION: Offering both EVAR and OGR to patients with rAAA leads to significant improvements in postoperative survival.

Combined enzymatic and antioxidative treatment reduces ischemia-reperfusion injury in rabbit skeletal muscle.

BACKGROUND: Ischemia/reperfusion (I/R) injury is characterized by the production of oxygen-free radicals leading to disturbances in vasomotility (microvascular constriction) and microvascular permeability (interstitial edema formation). The objective was to evaluate the effect of the combined antioxidative and enzymatic preparation Phlogenzym on I/R injury of skeletal muscle. MATERIALS AND METHODS: A rabbit hindlimb model of I/R (2.5/2 h) was used (IR group). Phlogenzym, containing rutin, trypsin, and bromelain, was applied enterally (60 mg/kg body weight) as a bolus 30 min prior to ischemia (Ph group). Sham-operated animals served as controls (CO group). Plasma malondialdehyde, potassium, and microvascular perfusion (monitored by laser flowmetry) were assessed. Histomorphometry and electron microscopy were performed from major adductor muscles. RESULTS: Two hours after reperfusion, potassium levels were significantly elevated in IR compared to Ph group (6.7 +/- 1.2 versus 4.9 +/- 0.9 mmol/l, P < 0.006). Enhanced lipid peroxidation, apparent by increased plasma malondialdehyde levels, was ameliorated in the Ph group (1.0 +/- 0.1 versus 0.7 +/- 0.1 nmol/ml, P < 0.0001). No-reflow (reduction of blood flow by 62% in IR group) was not observed in the Ph group (P < 0.004). Phlogenzym treatment prevented microvascular constriction (17.6 +/- 2.3 versus 12.6 +/- 1.1 microm(2), P < 0.0001) and mollified interstitial edema (21.5 +/- 2.0 versus 26.0 +/- 3.7%, P < 0.017), resulting in mild ultrastructural alterations in contrast to pronounced sarcolemmal and mitochondrial damage in untreated rabbits. CONCLUSIONS: Phlogenzym had a protective effect on skeletal muscle during I/R injury expressed by prevention of no-reflow and preservation of muscle tissue.

Endografting increases total volume of AAA repairs but not at the expense of open surgery: experience in more than 1000 patients.

PURPOSE: To compare the volume of open graft replacements (OGR) for abdominal aortic aneurysm (AAA) versus endovascular aneurysm repairs (EVAR) over time and after modifying selection criteria. METHODS: A review was conducted of 1021 consecutive patients who underwent AAA repair from 1989 through 2002: 496 elective OGRs for infrarenal AAAs (STANDARD), 289 elective EVARs for infrarenal AAAs, 59 complex OGRs for suprarenal AAAs, and 177 emergent OGRs for ruptured AAAs. Patients from 1995 to 2002 were divided into 2 groups based on shifting treatment strategies; 454 patients were treated by STANDARD or EVAR at the surgeon's discretion between 1995 and 2000 (post EVAR). The second group comprised 161 patients treated in 2001-2002 after the introduction of "high-risk" screening criteria (age > or = 72 years, diabetes mellitus, renal dysfunction, impaired pulmonary function, or ASA class IV) that dictated EVAR whenever anatomically feasible. For comparison, 170 STANDARD repairs performed in the 6 years prior to EVAR served as a control. RESULTS: While surgery for ruptured AAAs remained fairly stable over the 14-year period, the number of patients undergoing elective repair increased due to the implementation of EVAR. During the 6 years after its introduction, EVAR averaged 34.3 patients per year; after 2001, the annual frequency of EVAR increased to 41.5 (p > 0.05). In like fashion, the rate of STANDARD repairs increased to 41.3 patients per year versus 28.3 before EVAR (p = 0.032). ASA class IV patients increased by almost 9 fold in the recent period versus pre EVAR (p = 0.006). The overall mortality after elective infrarenal AAA repair decreased between the pre and post EVAR periods (6.5% versus 3.7%, p > 0.05) and fell still further to 1.2% in the most recent period (p = 0.021 versus pre EVAR). CONCLUSIONS: The implementation of an EVAR program increases the total volume of AAA repairs but does not reduce open surgical procedures. By allocating patients to EVAR or open repair based their risk factors, mortality was markedly reduced.

Involvement of nitric oxide in angiogenic activities of vascular endothelial growth factor isoforms.

We compared effects of vascular endothelial growth factor-121 (VEGF121) and vascular endothelial growth factor-165 (VEGF165) on generation of NO in HUVEC and the involvement of NO in VEGF121- and VEGF165-induced angiogenesis. VEGF stimulated synthesis of NO within seconds, reaching peak concentrations of 450 +/- 25 and 180 +/- 15 nmol/l for VEGF121, and VEGF165, respectively. The VEGF121 increased NO production for about 40 s while VEGF165-stimulated NO release lasted only for about 20 s. Accordingly, cGMP elevation was stronger in VEGF121- than in VEGF165-treated cells. The VEGF121 was a very weak mitogen but strong chemoattractant for HUVEC, whereas VEGF165 potently induced both cell proliferation and migration. NO appeared to be involved in the endothelial migration and morphogenesis but not in the proliferation. NO was also a permissive molecule for VEGF121- but not for VEGF165-induced capillary sprouting in spheroid culture. In conclusion, VEGF121 is a stronger stimulator of endothelial nitric oxide synthase (eNOS) activity, and angiogenic potential of VEGF121 is more reliant on NO contribution.

Endovascular treatment of a multimorbid patient with late AAA rupture after stent-graft placement: 1-year follow-up.

PURPOSE: To report successful endovascular management of a ruptured abdominal aortic aneurysm (AAA) in a multimorbid patient 40 months after primary stent-grafting. CASE REPORT: A 64-year-old man presented with hypotension, severe back pain, and abdominal distension. Immediate computed tomography revealed a proximal type I endoleak due to distal migration of the stent-graft with subsequent rupture of the aneurysm. The patient was hemodynamically unstable, and open surgery was refused because of severe comorbidities that were the indications for initial endovascular repair. The diameter of the proximal aneurysm neck required the use of a thoracic stent-graft that was overly long, which led to occlusion of the contralateral stent-graft limb supplying not only the left leg but also a left kidney transplant. A crossover bypass was implanted to revascularize both. CONCLUSION: Minimally invasive strategies, even when challenged by complex vascular reconstructions, offer the possibility of managing ruptured aortic aneurysms in patients unsuitable for open surgery.

Combined L-arginine and antioxidative vitamin treatment mollifies ischemia-reperfusion injury of skeletal muscle.

Enhanced production of superoxide in L-arginine-depleted environments and concomitant reduction of nitric oxide (NO) concentration are involved in ischemia-reperfusion (I/R) injury. Treatment with L-arginine or antioxidative vitamins alone and in combination was used to mollify I/R injury in skeletal muscle. Untreated rabbits were compared with those treated with L-arginine/antioxidative vitamin cocktail Omnibionta only, or a combination of L-arginine/ antioxidative vitamins during hind limb I/R (2.5 hours/2 hours). NO was continuously measured in vivo. Plasma malondialdehyde (MDA) served as the measure of oxygen free radical formation. Interstitial edema formation, microvessel diameter alterations, microvessel plugging, and blood flow changes were used as indicators of I/R injury. The MDA level in untreated animals 2 hours after reperfusion was significantly higher than in control animals (0.81 micromol/L +/- 0.14 micromol/L vs 0.57 micromol/L +/- 0.11 micromol/L; P<.05), indicating enhanced production of oxygen free radicals. This sequela paralleled the decreasing concentration of NO, which dropped below the detection limit (1 nmol/L) after reperfusion. Microvascular changes during I/R injury were expressed as a 40% decrease in microvessel diameter and adhesion of neutrophils in 20% of microvessels, which led to a consequent 60% reduction in blood flow, demonstrating "no reflow" (reperfusion failure after restoration of blood flow). The increase in the fraction of muscle interfiber area by 85% indicated prominent edema formation. Treatment with antioxidative vitamins alone had a minimally positive effect on edema formation and microvascular plugging, possibly by suppression of oxygen free radical production, as expressed by the reduction in plasma MDA levels. However, this therapy failed to preserve basal NO production and to protect from microvascular constriction and no reflow. Treatment with L-arginine alone had a stronger protective effect, maintaining basal NO production, further reduction of neutrophil plugging, abolition of microvascular constriction, and no reflow. The combination of antioxidative vitamins and L-arginine was the best treatment against I/R injury, expressed not only by the protection of microvessel constriction, but also by abolition of microvascular plugging, increase in NO production (68 nmol/L +/- 5 nmol/L) over the basal level (52 nmol/L +/- 7 nmol/L), and higher blood flow, as compared with treatment with L-arginine or antioxidative vitamins alone.

Lipoprotein (a) in patients with aortic aneurysmal disease.

OBJECTIVE: Lipoprotein (a) is an independent risk factor for atherosclerosis. Atherosclerotic degeneration is usually found in abdominal aortic aneurysms (AAAs), whereas thoracic aortic aneurysms (TAAs) caused by aortic dissection are not suggested to be linked pathogenetically to atherosclerosis. Lipoprotein (a) was analyzed in patients with AAA and TAA and in healthy individuals in relation to the extent of atherosclerosis. METHODS: Included in the case control study were patients with AAA (n = 75) and TAA with dissection (n = 39) and healthy control subjects (n = 43), for a total of 157 participants. Serum lipoprotein (a) was measured with nephelometry. Lipoprotein (a) levels were compared between age-matched and gender-matched paired samples of the three groups, and an association of lipoprotein (a), aortic aneurysm, and the extent of atherosclerosis was determined in multivariate analysis. RESULTS: Median lipoprotein (a) levels of patients with AAA and TAA and of control subjects were 18.9 mg/dL (interquartile range [IQR], <9.6 to 40.5), less than 9.6 mg/dL (IQR, <9.6 to 16.7), and less than 9.6 mg/dL (IQR, <9.6 to 16.3), respectively. Lipoprotein (a) was positively associated with the extent of atherosclerosis in patients and control subjects (P <.0001). Lipoprotein (a) levels of patients with AAA were significantly higher compared with patients with TAA (P <.0001) and control subjects (P <.0001). Multivariate analysis confirmed an independent association between lipoprotein (a) and AAA (P =.009). No significant differences of lipoprotein (a) were found between patients with TAA and control subjects (P =.3). CONCLUSION: The lipoprotein (a) serum level, an indicator of atherosclerosis, is significantly elevated in patients with abdominal aneurysms independently of cardiovascular risk factors and the extent of atherosclerosis. Patients with TAAs caused by dissection have lipoprotein (a) levels comparable with healthy individuals.