Ischemia-reperfusion damage is attenuated by GQ-11, a peroxisome proliferator-activated receptor (PPAR)-α/γ agonist, after aorta clamping in rats.

INTRODUCTION: Ischemia-Reperfusion (I/R) damage is one of the major challenges in cardiothoracic surgeries and in a pathological manner, is identified by exacerbated damage signals resulted from blood supply restriction and subsequent flow restoration and re­oxygenation. I/R damage includes cellular dysfunction and death, impairing tissue and organ function. Inflammation and oxidative stress are known to underlie either ischemia or reperfusion, leaded by HIF, TNF-α, NF-κB, IL-6 and ROS formation. However, the available approaches to prevent I/R damage has been unsuccessful so far. As agonists of peroxisome-proliferation activation receptor (PPAR) are described as transcription factors related to anti-inflammatory factors, we proposed to observe the effects of novel dual agonist, GQ-11, in I/R-related damage. METHODS: Male, Wistar rats, 60 days age and 305 g body weight average were treated with vehicle, pioglitazone or GQ-11 (20 mg/kg) for 7 consecutive days and were submitted to aorta clamping for 30 min followed by 3 h of reperfusion. 18F-fluorodeoxyglucose (18F-FDG), an analog of glucose associated with inflammation when accumulated, was observed in liver and bowel by positron emission tomography (PET). RESULTS: GQ-11 decreased 18F-FDG uptake in liver and bowel when compared to vehicle and pioglitazone. The treatment also modulated inflammatory markers IL-10, TGF-ß, IL-6, IL1-ß, TNFα, and CCL-2, besides antioxidant enzymes such as catalase, GPx and SOD. CONCLUSION: Inflammation and oxidative stress showed to be important processes to be regulated in I/R in order to prevent exacerbated responses that leads to cell/tissue dysfunction and death. PPAR agonists - including GQ-11 - might be promising agents in a strategy to avoid tissue dysfunction and death after cardiothoracic surgeries.

In Vivo Morphological Changes of the Femoropopliteal Arteries due to Knee Flexion After Endovascular Treatment of Popliteal Aneurysm.

Purpose: To evaluate morphological changes of the femoropopliteal (FP) arteries due to limb flexion in patients undergoing endovascular treatment of popliteal artery aneurysms (PAAs). Materials and Methods: Seven male patients (mean age 68 years) underwent endovascular treatment of PAA with a Viabahn stent-graft between January 2013 and December 2017. During follow-up, one contrast-enhanced computed tomography angiography (CTA) scan of the lower limbs was acquired for each recruited patient. A standardized CTA protocol for acquisitions in both straight-leg and bent-leg positions was used to visualize changes in artery shape due to limb flexion. Three-dimensional reconstruction of the FP segment was performed to compute mean diameter and eccentricity of the vascular lumen and to measure length, tortuosity, and curvature of the vessel centerline in 3 arterial zones: (A) between the origin of the superficial femoral artery and the proximal end of the stent-graft, (B) within the stent-graft, and (C) from the distal end of the stent-graft to the origin of the anterior tibial artery. Results: After limb flexion, all zones of the FP segment foreshortened: 6% in zone A (p=0.001), 4% in zone B (p=0.001), and 8% in zone C (p=0.07), which was the shortest (mean 4.5±3.6 cm compared with 23.8±5.7 cm in zone A and 23.6±7.4 cm in zone B). Tortuosity increased in zone A (mean 0.03 to 0.05, p=0.03), in zone B (0.06 to 0.15, p=0.005), and in zone C (0.027 to 0.031, p=0.1). Mean curvature increased 15% (p=0.05) in zone A, 27% (p=0.005) in zone B, and 95% (p=0.06) in zone C. In all zones, the mean artery diameter and eccentricity were not significantly affected by limb flexion. Conclusion: Limb flexion induces vessel foreshortening and increases mean curvature and tortuosity of the FP segment both within and outside the area of the stent-graft.

Kidney Preservation Using Renal Heterotopic Autotransplantation during Fenestrated Endovascular Aortic Repair for Complex Residual Type-A Aortic Dissection.

The treatment of type A acute aortic dissection is a challenge for the surgeon, and serious late complications may occur even after surgical repair. We report treatment after a type A postdissection thoracoabdominal aneurysm in a patient who previously underwent ascending aortic reconstruction using a biological aortic valve and Dacron prosthetic graft implantation in emergency conditions. The multistaged approach involved removing the right kidney and performing a heterotopic autotransplantation in the left iliac fossa before positioning a fenestrated endograft (celiac trunk, superior mesenteric artery, and left renal artery). The final step should have been the implantation of an aorto-bifurcated endograft, which, however, was postponed because the patient was injured during rehabilitation therapy. After 12 months, the computed tomography angiography scan showed complete thrombosis of the false lumen associated with large iliac entry tear closure and aortic diameter stability. These findings prompted us to desist from completing the aorto-bi-iliac implantation. This case demonstrates that in selected patients in whom treatment of a postdissection thoracoabdominal aneurysm with fenestrated endoprosthesis requires a challenging revascularization of the renal artery, a heterotopic kidney transplant using a mini-invasive technique may represent a viable and sufficiently safe alternative that guarantees renal blood perfusion.

Assessment of geometrical remodelling of the aortic arch after hybrid treatment.

OBJECTIVES: The aim of this study was to measure the morphological remodelling of the ascending aorta, aortic arch and thoracic aorta after aortic arch hybrid treatment including debranching and stent graft implantation. METHODS: Preoperative, 1-month and 1-year follow-up of computed tomography angiography scans of 22 patients were analysed to compute the lumen centreline from the aortic root to the coeliac trunk, and the following measurements were derived: the total centreline length, distance from the aortic root to the left subclavian artery, distance from the left subclavian artery to the distal landing zone. For both pre- and postoperative centrelines, the pointwise curvature was measured at the proximal and the distal landing zones. The mean curvature values of the whole aortic segment and the endografting region of the ascending and the descending aorta were measured. Surface outerline was computed as well, and curvature values at the endograft landing points were extracted. RESULTS: At the 1-month follow-up, centreline length were already significantly increased (382.66 ± 48.69 to 388.1 ± 50.75 mm; P = 0.01). Centreline pointwise curvature increased in the proximal (+29%, P = 0.011) and the distal zones (+63%, P = 0.004). Similarly, pointwise curvature of the outerline significantly increased in the proximal (+77%, P = 0.01) and the distal landing zones (+100%, P = 0.04). The centreline mean curvature increased in the ascending aorta (+7%, P = 0.02) and decreased in the endografting region (-3.3%, P = 0.004). No evidence of a relationship of such a remodelling with the type of endograft and the type of pathology was observed. This remodelling trend was confirmed by the analysis of 1-year computed tomography angiographies. CONCLUSIONS: Hybrid arch repair was associated with a significant elongation of the vessel and a significant increase in the curvature on the ascending aorta and the descending aorta and on the endograft proximal and the distal landing zones.

Twelve-year Follow-up Post-Thoracic Endovascular Repair in Type B Aortic Dissection Shown by Three-dimensional Printing.

BACKGROUND: Thoracic endovascular repair (TEVAR) is currently considered the therapy of choice for complicated type B acute aortic dissection (TBAAD). Although several papers have reported good outcomes at short- and medium-term follow-up, some questions still remain regarding the long-term durability and re-intervention rate during follow-up. METHODS: We describe a case of a patient originally treated with TEVAR for TBAAD complicated by impending aortic rupture. RESULTS: Endovascular repair successfully excluded the flow through the primary entry tear but during the 12-year follow-up period the patient experienced several complications and re-interventions. Various full-size three-dimensional (3D) models of the patient-specific vasculature were printed to better explain the different interventional interventions over the 12 years of follow-up and as a hands-on tool for medical education. CONCLUSIONS: The present case report, involving long-term follow-up, provides an example of the effectiveness and the safety of TEVAR for the treatment of complicated TBAAD shown at short and medium-term follow-up. However, the long-term complications that were observed in this patient during follow-up support the importance of lifelong CTA surveillance. Furthermore, this study confirms the capability of 3D printing technology as a powerful tool to support communication with patients and residents' education through the physical analysis of the real cases.

Midterm Follow-up Geometrical Analysis of Thoracoabdominal Aortic Aneurysms Treated with Multilayer Flow Modulator.

BACKGROUND: Aim of our study is the analysis of clinical results and aneurysmal sac evolution after multilayer flow modulator (MFM) placement, in patients with thoracoabdominal aortic aneurysms (TAAs). METHODS: All patients with asymptomatic TAA treated at our institution between 2012 and 2014 with MFM were retrospectively analyzed. Thirty-day evaluated outcomes were mortality and complications. Follow-up evaluated outcomes were mortality, aneurysm collateral branches patency, and reintervention. A geometrical analysis of 2-year follow-up computed tomography scans was carried out to evaluate the total aneurysm volume, the percentage of aneurysm growth, and the evolution of maximum aneurysm diameter. RESULTS: Seven patients (mean age: 71.8 years, range: 63-85 years) were considered in the study. Mean preoperative aneurysm diameter was 6.8 cm (range 6-8.3 cm). No 30-day mortality or complications were observed. Mean follow-up was 29.4 months. During follow-up, 3 deaths (42.8%) were observed, not related to MFM complications. Reintervention rate was 42.8%, occurred in all cases after 2-year follow-up; in 2 cases, the reintervention was necessary due to an excessive increase of the aneurysmal sac. During the follow-up, a mean growth rate of 6 mm/year (4 patients) for the diameter of the aneurysm external wall and a total aneurysm volume increase from 2.45 × 105 mm3 to 3.50 × 105 mm3 (4 patients) was evaluated. CONCLUSIONS: Our results have shown no mortality related to aneurysm rupture during the follow-up and high rate of reinterventions after MFM placement. Further geometrical analyses, based on the proposed approach, regarding a larger group of patients with long-term follow-up are required to draw indications about the MFM use.

Early evaluation of precise deployment with the new low-profile Zenith Alpha Thoracic Endoprosthesis in thoracic aortic disease.

BACKGROUND: Endovascular treatment of thoracic aortic disease currently allows to treat high-risk patients with better results than open repair. It represents the first option for treatment according to the most recent guidelines. The aim of the study is to evaluate the early results of the low-profile Zenith Alpha Thoracic Endoprosthesis (ZATE). METHODS: Between October 2012 and July 2015, 14 asymptomatic patients were treated with ZATE. 10 patients were male, mean age was 71, 7 years (range 58-85 years). 8 patients presented with atherosclerotic aortic aneurysm (7 thoracic aneurysm and 1 type I thoracoabdominal aneurysm), 2 chronic type B aortic dissection, 1 type IV endoleak 5 years after TEVAR, 3 aortic arch penetrating ulcers complicated by pseudoaneurysm. Hybrid staged procedures in 11 patients included 7 total aortic arch debranching (1 single [innominate] chimney stent-graft + carotid-carotid-subclavian), 2 carotid-carotid-subclavian artery bypass, 2 carotid-subclavian artery bypass. RESULTS: No 30-day mortality or major complications were observed. The mean length of stay was 7.3 days (range 4-14 days). Mean procedure time, X ray time and Contrast load were 115 minutes (range 90-150 minutes), 20 minutes (range 10-30) and 79 mL (range 40-120 mL) respectively. 25 stent-grafts were implanted. The mean follow-up was 21 months (range 14-32 months). No mortality and no major complications were observed during the follow-up. In case of arch debranching with landing 0 and 1 zone the mean distance between the beginning of the endoprosthesis and the debranching inflow vessel was 5.5±2.4 mm. CONCLUSIONS: The use of ZATE could be a viable alternative for treating patients with aortic arch proximal landing zone to facilitate the precise deployment. Larger case studies and longer follow-up are needed.

Inflammatory Response Modulation through a PPARγ Agonist during Surgically Induced Visceral Ischemia in an Animal Model.

BACKGROUND: Ischemia/reperfusion (I/R) injury represents one of the most severe complications in vascular surgery where cross-clamping of the aorta and subsequent visceral ischemia are a recurrent issue. The literature describes a family of nuclear receptors, that is, peroxisome proliferator-activated receptors (PPARs), in particular PPARγ isoform, which are important modulators of vascular inflammation resulting from I/R injury. The aim of our study is to evaluate how PPARγ agonist administration could reduce local and systemic inflammatory response after I/R injury during aortic supraceliac clamping in animal model. METHODS: Our model includes 16 rats divided as follows: 8 rats in the placebo control group (PlacG) were operated on without having been administered of any drugs during the preoperative period, whereas the 8 rats in the pioglitazone group (PioG) were pretreated with pioglitazone. Renal and visceral ischemias were induced in the rats by supraceliac aortic clamping. Rats were sacrificed after surgery, and then, we collected blood samples to measure serum levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) and one of the kidneys and a segment of the liver to perform histological analysis. RESULTS: Considering both cytokines in the PioG, there has been a negative trend in serum concentrations, whereas in the PlacG, we observed an increasing trend. The high standard deviation observed in our study is mainly due to the small population of the cohort. Histologic examination of the kidney showed more severe damage in the placebo group as compared to the PioG with more evident differences in tubular and tubulointerstitial scores. CONCLUSIONS: Our observations show that administering pioglitazone can partially reduce secondary inflammatory response in the ischemic insult especially in endothelial and perivascular tissues.

A retrospective study on short-term results with straight graft vs. bifurcated graft in abdominal aortic aneurysms: a single center experience.

BACKGROUND: The aim of this paper was to compare in a retrospective study the outcome of aortoaortic graft (straight graft) versus aortoiliac graft (bifurcated graft) with regards to periprocedural and 30-day after surgery complications. METHODS: From January 2004 to December 2009 377 patients underwent elective open surgery for infrarenal abdominal aortic aneurysm. Data were collected in a dedicated database. Group A includes patients treated with straight graft (N.=186) whereas group B, patients treated with bifurcated graft (N.=191). Outcome data include duration of surgical procedure, blood loss, peri- and postprocedural complications, hospital stay, 30-day mortality and complications. Following some authors, we set our cut-off for choosing a bifurcated graft when one or both Iliac Arteries were wider than 18 mm in diameter and the patient had a reasonable life expectancy. RESULTS: Duration of surgical procedure was 183 minutes in the group A vs. 216 minutes in the group B (P<0.01). Blood loss was 554 mL and 720 mL, in the groups A and B respectively (P<0.01). The difference between other results evaluated was not statistically significant. CONCLUSIONS: In statistics terms, this retrospective study showed no relevant differences between straight graft and bifurcated graft with regard to mortality and major complications during the peri- and postoperatory period. Hence, as a conclusion, we could assert that if the iliac artery diameter is 18 mm a bifurcated graft could be used, without any increase in morbidity and mortality rates.

Treatment with aromatase inhibitors and markers of cardiovascular disease.

PURPOSE: The cardiovascular effects of estrogen deprivation induced by aromatase inhibitors are unknown. We carried out a cross-sectional study to evaluate the effect of estrogen deprivation induced by aromatase inhibitors on markers of cardiovascular risk. METHODS: We enrolled 410 postmenopausal women: 200 consecutive breast cancer patients treated with aromatase inhibitors for a median of 53 months (range 23-122) and 210 volunteer controls. Carotid intima-media thickness, presence of carotid stenosis, and presence of abdominal aortic aneurism were evaluated through an ultrasound examination. RESULTS: Average carotid intima-media thickness was 0.97 ± 0.02 mm and 1.08 ± 0.02 mm for breast cancer group and control group, respectively (p < 0.005). The incidence of carotid stenosis in the two groups was similar: 24.2 % in the breast cancer group and 28.6 % in the control group (OR 0.80; 95 % CI 0.51-1.25; p = 0.32). No aneurismatic dilatation of the aorta was recorded. Average abdominal aortic diameter was 14.9 ± 2.4 mm in the breast cancer group and 15.0 ± 2.4 mm in the control group. CONCLUSIONS: Our study showed no association between treatment with aromatase inhibitors for five or less years and increased carotid intima-media thickness and higher prevalence of carotid stenosis or abdominal aortic aneurism. The lack of impact on these markers suggests that cardiovascular risk is not increased by treatment with aromatase inhibitors.

In Vitro Evaluation of Upstream and Downstream Influences on Blood Pressure of the Hybrid Treatment of Thoracoabdominal Aortic Aneurysms.

BACKGROUND: The aim of our study was to assess, by means of an experimental model, whether different geometries in retrograde bypass and stent-graft deployment may affect upstream and downstream blood pressure in hybrid treatment. METHODS: An in vitro model of the arterial circulation has been prepared, which consists of a peristaltic pump, silicon tubes with geometrical and mechanical properties close to realistic arteries, a terminal reservoir kept at constant pressure, and a sequence of pressure transducers. The system allows us to study the pressure wave propagation in physiological conditions and simulate the patient's conditions as a result of debranching in 2 different configurations. RESULTS: In configuration 1, the mean pressure value (Kpa) was 4.72 in silicone tube before stent graft and debranching, 4.59 in visceral and renal bypass, and 4.38 in silicone tube after stent graft and debranching. In configuration 2, the mean pressure value (Kpa) was 5.22 in silicone tube before stent graft and debranching, 4.48 in visceral and renal bypass, and 4.99 in silicone tube after stent graft and debranching. CONCLUSION: The experimental data suggest that the debranching geometry and the material of the grafts and stent grafts change significantly the physiological arterial pressure possibly leading to an augmented pressure upstream of the stent grafts, owing to retrograde pressure waves toward the heart, and a decreased pressure downstream visceral and renal arteries.

A true giant aneurysm of the anterior tibial artery.

Aneurysms of the anterior tibial artery are rare. We will describe a case of a woman with an asymptomatic true aneurysm of the anterior tibial artery. The patient presented with a pulsatile mass in the lateral face of the distal portion of the left leg, and both ultrasound examination and computed tomography angiography scan showed a giant aneurysm of the anterior tibial artery. We chose open treatment.