EVAR with Flared Iliac Limbs has a High Risk of Late Type 1b Endoleak.

INTRODUCTION: Re-interventions are still the Achilles' heel of endovascular aneurysm repair (EVAR). Ectatic common iliac arteries (CIA) can be treated with flared iliac limbs but a dilated artery used as sealing zone could increase the risk of a late type 1b endoleak. The aim of the present analysis was to evaluate the risk of late type 1b endoleak after EVAR in patients with CIA limbs ≥20 mm compared with those <20 mm. METHODS: A retrospective analysis was performed of patients treated by EVAR at the study institution between 2006 and 2012, including patients with available information about the type of iliac stent grafts and a minimum follow-up (FU) of 3 years with contrast enhanced CT, or those that had developed a type 1b endoleak earlier. The cohort was divided into two groups: Group I included iliac limbs with a distal diameter <20 mm, and Group II included all iliac limbs with a distal diameter ≥20 mm. RESULTS: Of 692 limbs (346 patients), 239 limbs (34.5%) from 129 patients were included in the analysis. Mean CT FU was 53 months, 178 had an iliac stent graft diameter <20 mm (Group I), and 61 a diameter of ≥20 mm (Group II). Mean oversizing for iliac limbs was 17.2% (IQR 14) and there was no case of immediate type 1b endoleak. For the whole group, 18 type 1b endoleaks occurred during FU (7.5%) after a mean of 37.7 months (range 4-96). Eleven of 61 (18%) iliac limbs in Group II developed a type 1b endoleak during FU in contrast to 7/178 (3.9%) in Group I (OR 5.3, 95% CI 1.98-14.59, p = 0,001). The ROC curve analysis indicated a limb diameter of 19 mm as a cutoff value for a higher probability of developing a type 1b endoleak. CONCLUSION: Patients treated with iliac limbs ≥20 mm had a fivefold higher risk of late (mean 37 months) type 1b endoleak compared with patients treated with a distal iliac limb diameter <20 mm.

INCRAFT® Stent-Graft System: one-year outcome of the INNOVATION Trial.

AIM: Endovascular repair has surpassed open surgical treatment as the most common procedure in patients with abdominal aortic aneurysms (AAA), yet its applicability remains limited to those with aortoiliac anatomy suitable for the introduction and deployment of the devices. The current study was performed to assess the safety and efficacy of INCRAFT® (Cordis Corporation, Bridgewater, NJ), an ultra-low-profile device for the treatment of AAA. METHODS: The INNOVATION study is a first in human prospective, multicenter trial involving 6 centers in Europe. From March 2010 to June 2011 60 patients with asymptomatic AAA were treated with the INCRAFT® bifurcated Stent-Graft System. The main inclusion criteria were a proximal aortic neck of 15 mm or more in length and up to 27 mm in diameter; iliac landing zones greater than 10 mm in length and between 9 and 18 mm in diameter; an access vessel large enough to accept the 14F outer diameter of the delivery system; and an aortic bifurcation >18 mm in diameter. The primary endpoint was technical success at one-month; one-year safety endpoints included the absence of device- or procedure-related major adverse events; absence of type I or III endoleaks; and maintenance of device integrity through one year of follow-up. RESULTS: Among 60 patients treated at six centers, the primary endpoint was met in 56 of 58 patients (97%; 95% CI, 88-100%) who came back for one month follow-up, two patients did not come back for their one month follow-up assessments but remained enrolled in the study. Fifty-six had one-year follow-up data showing 100% freedom from aneurysm enlargement with absence of type I and III endoleaks in all patients. There were two patients (3.6%) with a type Ia endoleak which was successfully treated with secondary endovascular intervention in both occasions. Core laboratory evaluation of the postoperative imaging studies documented absence of endograft migration, stent fracture, or limb occlusion. A single patient (1.8%) died within one year due to sepsis unrelated to the AAA. CONCLUSION: The results of the INNOVATION study with the INCRAFT® Stent-Graft are encouraging, with satisfactory clinical outcome and device durability through one-year of follow-up. The INCRAFT® device is a novel ultra-low-profile endograft that holds promise to broaden the patient population eligible for endovascular aneurysm repair.

Endovascular treatment of a ruptured aneurysm of the inferior thyroid artery. Case report and literature review.

Aneurysms of the inferior thyroid artery are rare. The natural course of these aneurysms seems to be unfavourable, why aneurysm exclusion is recommended in the literature. Open surgical repair is complex why endovascular exclusion seems to be an appealing alternative. We present a patient who developed dysphagia and respiratory distress caused by a ruptured aneurysm of the right inferior thyroid artery. Successful coil embolization of the aneurysm is described along with a review of the literature. Despite the very rare data of these aneurysms, all reported cases of endovascular treatment (n=3) showed favourable results, therefore aneurysm embolization seems to be a feasible and safe alternative to open surgery, especially in emergency cases.

Radiation therapy induced modulation of wound healing at experimental vein graft anastomoses.

OBJECTIVES: The aim of this study was to investigate if radiation therapy (RT) favorably modulates wound healing at vein graft anastomoses. MATERIALS AND METHODS: Jugular vein grafts were sewn into carotid arteries in 32 rats which were randomly divided into two groups: RT (gamma source, 14 Gray, n=16) and control (C, sham irradiation, n=16). Grafts and adjacent arteries were analyzed at 2 (n=8) and 8 weeks (n=8) by histology, immunohistochemistry, and morphometry. RESULTS: Although, RT did not reduce the overall occurrence of intimal hyperplasia, the distribution differed. RT led to a reduction of intimal hyperplasia in arterial segments (median: C: 41.873 microm2; RT: 6.452 microm2, p < 0.0007). In contrast, RT augmented intimal hyperplasia in vein grafts (median: C: 30.287 microm2; RT: 90.455 microm2, p < 0.014). Vein graft diameters after RT were enlarged (median: C: 2.098 microm; RT: 3.381, p < 0.031). Over 80% of the cells were of mesenchymal origin in both groups. CONCLUSIONS: RT reduced intimal hyperplasia in arterial segments. However, RT led to graft dilatation and increased intimal hyperplasia in vein grafts. RT did not favorably modulate the vascular wound healing response in this model.

Modulation of human adventitial fibroblast function by photodynamic therapy of collagen matrix.

OBJECTIVES: Photodynamic therapy (PDT) is a promising strategy to limit restenosis. PDT depletes the resident cells from the vessel wall without adventitial cell ingrowth. This study was undertaken to further explore the mechanisms by which PDT of matrix acts on key mechanisms in the development of restenosis. MATERIALS AND METHODS: Control and PDT-treated collagen type-I matrix gels were prepared. Thereafter, untreated human fibroblasts were seeded on matrix gels (n=12). Fibroblast proliferation and invasive migration were quantified by calibrated phase contrast microscopy. Fibroblast bFGF and TGF-beta1 mRNA expression were analyzed using a quantitative real-time reverse transcription polymerase chain reaction. RESULTS: Fibroblast proliferation on PDT-treated matrix gels was reduced by 30 and 76% after 3 and 7 days, respectively (3 days: P

Prostacyclin release from the human saphenous vein in diabetics in lower than in nondiabetics.

The balance between prostacyclin and thromboxane has been suggested to be of great importance for the maintenance of patency in veins. In order to investigate prostacyclin and thromboxane release, segments from the human saphenous veins were investigated in 53 patients. Twenty-seven patients (10 males, 17 females) underwent surgery for varicose veins. Twenty-six patients (14 nondiabetics, 12 diabetics) underwent surgery for lower limb ischemia (rest pain or gangrene) with use of the saphenous vein as arterial conduit. Vein segments were gently excised and perfused ex vivo for five 15 minute periods, with a balanced salt solution and determination of the stable degradation products 6-keto-PGF1 alpha and TxB2. Saphenous veins from patients with varicose veins had an initial prostacyclin release of 61 +/- 13 pg/mm2/15 min declining to 4 +/- 1 pg/mm2/15 min after 60 min (p < 0.001) and increasing after addition to arachidonic acid to 37 +/- 7 pg/mm2/15 min (p < 0.001). Segments from nondiabetic patients with lower limb ischemia did not differ from those of varicectomy patients, but diabetic segments had a significantly lower prostacyclin release than both these groups, 34 +/- 11 pg/mm2/15 min, 1 +/- 1 pg/mm2/15 min, and 7 +/- 5 pg/mm2/15 min, respectively (p < 0.05). The addition of arachidonic acid failed to increase the prostacyclin release in diabetics. Three patients from each group were studied regarding thromboxane release and there was almost no detectable thromboxane in any group. These findings suggest that diabetics have a lowered prostacyclin release from the saphenous vein and that the deficiency is at the cyclo-oxygenase level.(ABSTRACT TRUNCATED AT 250 WORDS)

Papaverine effects on PGI2 and TXA2 release from the canine vascular wall.

Operative manipulation of blood vessels might lead to spasm, thereby destroying the endothelial cell function: the spasm can be prevented by the vasodilator papaverine. To study if this was mediated via the prostanoid pathway the following investigation was undertaken: canine jugular veins and carotid arteries were dissected with or without papaverine. Vessel segments were then perfused with Hank's balanced salt solution for five times 15 min. Prostacyclin was measured as the stable degradation product 6-keto-PGF1 alpha and thromboxane as TXB2, by radioimmunoassay. Control arterial segments' 6-keto-PGF1 alpha release was initially 129.5 + 20.1 pg/mm2/15 min, and 29.7 + 10.4 after 60 min (p less than 0.05 vs initial value) and responded to arachidonic acid (AA) with an increase to 139.2 +/- 23.1 pg/mm2/15 min (p less than 0.05). Segments treated with papaverine had the same release as the controls. In venous segments there was a lower initial release (p less than 0.05) from segments given papaverine than from controls, but this was more likely an effect of papaverine on the assay. There was no difference in release of prostacyclin from segments given papaverine in the perfusate compared to controls when using 125I tracer. When using 3H tracer including absorption of free antigen to dextran coated charcoal, papaverine displaced the free tracer giving artificially low values. There was no effect of papaverine given intraoperatively on the TXB2 release, neither from arteries nor from veins. In another experiment the vessel wall tension was examined and the cyclooxygenase inhibitor diclofenac did not inhibit the vasodilating effect of papaverine.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of plasma on PGI2 release from prolonged perfused canine veins.

Prostacyclin release from endothelial cells in culture appears increased by the presence of plasma, but occurrence of a similar phenomenon in intact vessels has not been established. In the present investigation release of 6-keto-PGF1 alpha, the stable breakdown product of prostacyclin, was quantitated from canine veins perfused ex vivo for 15 minute periods, using three different perfusates: 1) Hank's balanced salt solution (HBSS), 2) 20% platelet poor plasma (PPP) derived from heparinized blood, in HBSS, and 3) 20% PPP in HBSS with added arachidonic acid (AA). No differences in initial 6-keto-PGF1 alpha release existed among the three perfusates. However, PPP and PPP + AA solutions were associated with lesser declines in release, than occurred with HBSS alone, these differences being statistically significant after 60 min of perfusion (p less than 0.05). When PPP derived from heparinized and citrated blood rather than from only heparinized blood was used, there was a significantly lower release of prostacyclin (p less than 0.05). The latter may be due to citrate binding of calcium. These data indicate that autologous plasma does not alter initial prostacyclin release from freshly harvested canine veins, but that it weakens the decline in release usually following prolonged periods of perfusion.

Prostanoid release from ex vivo perfused canine arteries and veins: effects of prolonged perfusion, intermittent perfusion, as well as exposure to exogenous arachidonic acid, thrombin and bradykinin.

Regulation of prostanoid release from ex vivo perfused vessel segments is not fully understood. A series of perfusion experiments were performed with canine arteries and veins to define certain regulatory phenomena. Arteries were perfused with pulsatile flow of 90 ml/min at a pressure of 100 mmHg, and veins with nonpulsatile flow of 90 ml/min at a pressure of 7 mmHg. Segments were perfused with Hanks' balanced salt solution for five 15-min periods with the perfusate exchanged after each study period. With onset of perfusion, there was an initial burst of prostacyclin release to 127 +/- 40 pg/mm2, declining to 32 +/- 10 pg/mm2 after 60 minutes (p less than 0.005). If perfusion continued for 5.5 hours, there was a stable release period between 1 and 3 hours, followed by a very slow decline. At that time addition of arachidonic acid (AA) increased prostacyclin release six-fold (p less than 0.01). Vessels perfused for 1 hour and then rested for another hour, responded to reperfusion at the second onset of flow with a two-fold increase in prostacyclin release (p less than 0.01). Vessels perfused with thrombin, bradykinin or AA (either added to each perfusate or only to the last perfusate) exhibited greater prostacyclin release than did control segments. Release of thromboxane steadily declined with time in all parts of the study, and only increased with the addition of AA to the perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial 6-keto-PGF1 alpha and TxB2 release in ex vivo perfused canine vessels: effects of pulserate, pulsatility, altered pressure and flow rate.

Certain experimental conditions are known to influence the release of prostacyclin and thromboxane from the vessel wall. The specific effects of altered pulsatility, pressure, and flow rate on intraluminal release of 6-keto-PGF1 alpha and thromboxane B2 were assessed in canine arteries perfused ex vivo for five 15 min periods with arachidonic acid (AA) added during the last period. Control arteries were perfused at 100 mmHg with pulsatile flow of 90 ml/min. Experimental arteries were perfused at 7, 50 and 200 mmHg with pulsatile flow of 90 ml/min, and at 100 mmHg pressure with pulsatile flow of 20, 60, 130 and 180 ml/min, as well as at 100 mmHg with 90 ml/min nonpulsatile flow. Perfusion pump rates of 44 and 96 beats/min were also assessed. The lowest perfusion pressure, 7 mmHg, resulted in a lesser initial release of prostacyclin compared to higher pressures, and there was a tendency to a higher release of prostacyclin with increasing pressures. There was also a tendency for a lesser response to AA in arteries perfused at 200 mmHg, perhaps due to endothelial cell damage. Nonpulsatile flow was associated with a decreased initial release of prostacyclin, and diminished release following addition of AA when compared to pulsatile flow. Altered flow rate elicited no difference in prostacyclin release, although there was a tendency towards a lesser release when perfused at 20 ml/min compared to 130 ml/min or 180 ml/min. Thromboxane release was decreased by nonpulsatile flow but was otherwise unaffected by the experimental conditions tested. It is concluded that pulsatility enhances release of prostacyclin from arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of preexcisional heparin anticoagulation on excised canine vein and artery prostanoid production.

The effect of heparin, administered prior to vessel dissection and excision, on the luminal release of prostanoids from an excised vessel was assessed. Eight adult mongrel dogs underwent removal of the jugular vein and carotid artery on one side, followed by intravenous administration of heparin sodium (150 IU/kg) and subsequent removal of these same vessels from the contralateral neck. The excised vessels were perfused in an ex vivo system with Hanks' balanced salt solution for five consecutive 15-min periods. Prostacyclin release (measured as 6-keto-PGF1 alpha) and thromboxane A2 (measured as thromboxane B2) release into the perfusate were quantitated by radioimmunoassay. Vessel segments were studied with and without first period thrombin stimulation (2 U/ml) and with arachidonic acid (4 micrograms/ml) stimulation during the last perfusion period. Vein segments following heparin administration exhibited greater prostacyclin production than veins not exposed to heparin. This effect did not occur in arteries. Heparin did not influence thromboxane A2 release. Luminal endothelial cell coverage was not affected by the presence or absence of heparin. Thus heparin anticoagulation prior to dissection and excision of a vein, may enhance early preservation of its endothelial cell function as evident by increased luminal release of prostacyclin.

Comparison of static incubation versus physiologic perfusion techniques for quantitation of luminal release of prostacyclin and thromboxane in canine arteries and veins.

Intraluminal release of 6-keto-PGF1 alpha and TxB2 in ex vivo canine arteries and veins was assessed during five consecutive 15-min periods using static incubation and physiologic perfusion techniques. Arterial segments were perfused with 90 ml/min pulsatile flow at 100 mm Hg and vein segments with 90 ml/min nonpulsatile flow at 7 mm Hg. During the final 15-min period vessels were stimulated with arachidonic acid (AAS). Perfusion of vein segments caused a higher release of 6-keto-PGF1 alpha during the first 30 min (P less than 0.05) and following AAS (P less than 0.05) than did static incubation. Perfused arterial segments exhibited a higher release than did incubated segments of 6-keto-PGF1 alpha for 45 min (P less than 0.01) as well as following AAS (P less than 0.01). TxB2 release was higher during the entire observation period in perfused arteries and veins compared to incubated vessels (P less than 0.01 and less than 0.05, respectively). There was no correlation between the amounts of 6-keto-PGF1 alpha or TxB2 released when comparing values obtained by one technique to values obtained by the other (P greater than 0.1). These data suggest that flow related shear stress alters vascular prostanoid production, and that such should be accounted for when interpreting results of studies on prostacyclin and thromboxane release from intact vessels.

Influence of pressure, flow rate, and pulsatility on release of 6-keto-PGF1 alpha and thromboxane B2 in ex vivo-perfused canine veins.

The influence of pressure, flow, and pulsatility on the release of prostacyclin (measured as 6-keto-PGF1 alpha) and thromboxane (measured as TxB2) was assessed in canine jugular veins perfused ex vivo with Hanks' balanced salt solution for five consecutive 15-minute periods. Control segments were perfused at 7 mm Hg with nonpulsatile flow at a rate of 90 ml/min, whereas experimental segments were perfused with pulsatile flow as well as nonpulsatile flow at pressures of 50 or 100 mm Hg and flow rates of 60 or 130 ml/min. Prostacyclin release from control segments during the first 15-minute period was 49.5 +/- 7.4 pg/mm2/15 min, which declined to 13.9 +/- 2.5 pg/mm2/15 min after 60 minutes (p less than 0.002). Arachidonic acid stimulation during the last 15-minute perfusion period increased the release to 56.1 +/- 9.4 pg/mm2/15 min (p less than 0.002). Thromboxane release from control segments was initially 4.4 +/- 1.2 pg/mm2/15 min, which declined to 0.8 +/- 0.2 pg/mm2/15 min after 60 minutes (p less than 0.002), and subsequently increased with arachidonic acid stimulation to 1.3 +/- 0.1 pg/mm2/15 min (p less than 0.01). In contrast to control perfusion conditions, changes in nonpulsatile flow rates did not affect prostacyclin release, whereas thromboxane release was lower when perfused at 60 ml/min. Pressures of 50 and 100 mm Hg increased the initial release of prostacyclin. Similarly, pulsatile flow enhanced prostacyclin release at both low and high pressures, being more pronounced with the latter.(ABSTRACT TRUNCATED AT 250 WORDS)