A comparison of balloon injury models of endovascular lesions in rat arteries

BACKGROUND: Balloon injury (BI) of the rat carotid artery (CCA) is widely used to study intimal hyperplasia (IH) and decrease in lumen diameter (LD), but CCA's small diameter impedes the evaluation of endovascular therapies. Therefore, we validated BI in the aorta (AA) and iliac artery (CIA) to compare it with CCA. METHODS: Rats underwent BI or a sham procedure (control). Light microscopic evaluation was performed either directly or at 1, 2, 3, 4 and 16 weeks follow-up. The area of IH and the change in LD (LD at 16 weeks minus LD post BI) were compared. RESULTS: In the BI-groups the area of IH increased to 0.14 ± 0.08 mm(2) (CCA), 0.14 ± 0.03 mm(2) (CIA) and 0.12 ± 0.04 mm(2) (AA) at 16 weeks (NS). The LD decreased with 0.49 ± 0.07 mm (CCA), compared to 0.22 ± 0.07 mm (CIA) and 0.07 ± 0.10 mm (AA) at 16 weeks (p < 0.05). The constrictive vascular remodelling (CVR = wall circumference loss combined with a decrease in LD) was -0.17 ± 0.05 mm in CIA but absent in CCA and AA. No IH, no decrease in LD and no CVR was seen in the control groups. CONCLUSIONS: BI resulted in: (1.) a decrease in LD in CCA due to IH, (2.) a decrease in LD in CIA due to IH and CVR, (3.) no change in LD in AA, (4.) Comparable IH development in all arteries, (5.) CCA has no vasa vasorum compared to CIA and AA, (6.) The CIA model combines good access for 2 F endovascular catheters with a decrease in LD due to IH and CVR after BI

Электродуговая атмосферная переработка пищевых полимеров в наноразмерный углеродный порошок

ObjectiveParaplegia after thoracoabdominal aortic aneurysm (TAAA) repair mainly occurs in patients with Crawford extent I and II. We assessed the impact of monitoring spinal cord integrity and the subsequent adjusted surgical maneuvers on neurologic outcome in repairs of type I and II TAAAs.MethodsSurgical repair of TAAAs was performed in 112 consecutive patients with extent type I (n = 42) and type II (n = 70) aneurysms. The surgical protocol included cerebrospinal fluid drainage, moderate hypothermia, and left heart bypass with selective organ perfusion. Spinal cord function was assessed by means of monitoring motor evoked potentials (MEPs). Significant decreased MEPs always generated adjustments, including raising distal aortic and mean arterial pressure, reattachment of visible intercostal arteries, or endarterectomy of the excluded aortic segment with revascularization of back bleeding intercostal arteries.ResultsMotor evoked potential monitoring could be achieved in all patients. By maintaining a mean distal aortic pressure of 60 mm Hg, MEPs were adequate in 82% of patients. Increasing distal aortic pressure restored MEPs in all patients. In 19 patients (17%), MEPs decreased significantly during aortic cross-clamping because of critical spinal cord ischemia. MEPs returned in all patients after spinal cord blood flow was re-established except in three patients with type II TAAA in whom MEPs could not be restored, and absent MEPs at the end of the procedure corresponded with neurologic deficit. Delayed paraplegia developed in two patients owing to hemodynamic instability with insufficient mean arterial blood pressure to maintain adequate spinal cord perfusion.ConclusionMonitoring MEPs is a highly reliable technique to assess spinal cord ischemia during TAAA repair. A surgical protocol including cerebrospinal fluid drainage, left heart bypass, and monitoring of MEPs can reduce the paraplegia rate significantly. Adjusted hemodynamic and surgical strategies induced by changes in MEPs could restore spinal cord ischemia in most patients, preventing early and late paraplegia in all type I patients. In type II patients, early paraplegia occurred in 4.2% and delayed neurologic deficit in 2.9%. Despite all available measures, complete prevention of paraplegia in type II aneurysms seems to be unrealistic

Glomerular filtration rate is superior to serum creatinine for prediction of mortality after thoracoabdominal aortic surgery

BackgroundClinically evident renal disease (dialysis, history of renal insufficiency, or serum creatinine >2.0 mg/dL) is a known risk factor for mortality after thoracoabdominal aortic aneurysm repair. We extended this concept to the questions of whether subclinical renal disease is also a risk factor and how best to identify subclinical disease. We hypothesized that the glomerular filtration rate (GFR) would be a more sensitive determinant of renal function than serum creatinine alone.MethodsBetween 1991 and 2004, we repaired 1106 thoracoabdominal aortic aneurysms and descending thoracic aortic aneurysms. The median age was 67 years. There were 400 (36%) women and 706 (64%) men. We estimated GFR by using the Cockcroft-Gault equation. We divided baseline serum creatinine and baseline GFR into quartiles and estimated the association of the quartiles with 30-day postoperative mortality by χ2 testing. We further subdivided the population into patients with and without clinically evident renal disease and repeated the analysis in the patients without clinically apparent disease (n = 869).ResultsClinically apparent renal disease was highly associated with 30-day mortality (odds ratio, 3.2; P < .0001). In all patients, serum creatinine quartile and GFR quartile were also both highly significantly associated with 30-day mortality (P < .0001). In patients without clinically apparent renal disease, both creatinine and GFR predicted additional mortality, but GFR was a much stronger predictor (P < .02 for creatinine vs <.0001 for GFR). In these patients, mortality ranged from 5% in the best GFR quartile to 27% in the worst. Taken as continuous variables in logistic regression equations, serum creatinine had no discrimination in patients without clinical disease (P = .73), whereas GFR remained strong (P <.0001).ConclusionsPreoperative renal function is an important determinant of early mortality even in patients without clinically evident disease. Estimated GFR is a much more powerful determinant of mortality risk than serum creatinine alone

10-Year Paclitaxel Dose-Related Outcomes of Drug-Eluting Stents Treated Below the Knee in Patients with Chronic Limb-Threatening Ischemia (The PADI Trial)

Purpose: Recently, two meta-analyses concluded that there appears to be an increased risk of long-term mortality of paclitaxel-coated balloons and stents in the superficial femoral and popliteal artery, and paclitaxel-coated balloons below the knee. In this post hoc study of the PADI Trial, we investigated the long-term safety of first-generation paclitaxel-coated drug-eluting stents (DES) below the knee and the dose–mortality relationships of paclitaxel in patients with chronic limb-threatening ischemia (CLI). Materials and Methods: The PADI Trial compared paclitaxel-coated DES with percutaneous transluminal angioplasty with bail-out bare-metal stents (PTA ± BMS) in patients with CLI treated below the knee. Follow-up was extended to 10 years after the first inclusion, and survival analyses were performed. In addition, dose-related mortality and dose per patient weight-related mortality relations were examined. Results: A total of 140 limbs in 137 patients were included in the PADI Trial. Ten years after the first inclusion, 109/137 (79.6%) patients had died. There was no significant difference between mortality in the DES group compared with the PTA ± BMS group (Log-rank p value = 0.12). No specific dose-related mortality (HR 1.00, 95% CI 0.99–1.00, p = 0.99) or dose per weight mortality (HR 1.05, 95% CI 0.93–1.18, p = 0.46) relationships were identified in the Cox-proportional Hazard models or by Kaplan–Meier survival analyses. Conclusions: There is a poor 10-year survival in both paclitaxel-coated DES and PTA ± BMS in patients with CLI treated below the knee. No dose-related adverse effects of paclitaxel-coated DES were observed in our study of patients with CLI treated below the knee. Level of Evidence: The PADI Trial: level 1, randomized clinical trial

Photodynamic therapy inhibits transforming growth factor β activity associated with vascular smooth muscle cell injury

AbstractPurpose: The multifunctional cytokine, transforming growth factor β1 (TGF-β), plays an important role in the development of injury-associated intimal hyperplasia (IH). Strategies to suppress local TGF-β activity may have a clinical potential to prevent restenosis caused by IH. Photodynamic therapy (PDT) involves the local generation of cytotoxic free radicals by light activation of photosensitizer dyes and has been shown to inhibit experimental IH. This study investigated whether PDT-generated free radicals can affect TGF-β activity in a biologic system using vascular smooth muscle cells (SMCs).Methods: The release and activation of TGF-β by injured SMCs in culture was compared between mechanical injury and PDT. Mechanical injury was induced with a rubber policeman, and PDT was performed with the photosensitizer chloroaluminum sulfonated phthalocyanine (5 μg/ml) and 675 nm laser light at subtherapeutic 10 J/cm2 and the in vivo therapeutic dose of 100 J/cm2. Cell viability was assessed by the tetrazolium salt conversion assay, and active and total (active + latent) TGF-β was determined by enzyme-linked immunosorbent assay in the conditioned media of SMCs 24 hours after treatment. Functional TGF-β activity was assessed by inhibition of endothelial cell mitogenesis.Results: Both forms of injury severely reduced (p < 0.0005) SMC viability to less than 15%. In untreated SMC conditioned media, only 14.5% of the total TGF-β was active (27.7 ± 8.7 pg per 1 × 105 cells). However, after mechanical injury and PDT with 10 J/cm2, there was a significant increase (p < 0.02) in active TGF-β (60.1 ± 10.1 pg and 48.6 ± 21.0 pg, respectively), despite a total reduction of approximately 50%. In contrast to this result, PDT with 100 J/cm2 did not result in increased levels of active TGF-β (8.1 ± 3.5 pg), despite having similar levels of total TGF-β. Consequently, the conditioned media of SMCs that had 100 J/cm2 PDT did not inhibit endothelial cell mitogenesis as compared with the conditioned media of SMCs with mechanical injury and 10 J/cm2 PDT (p < 0.0002).Conclusions: This report describes two novel findings: (1) injury to SMCs in vitro induces the conversion of biologically latent TGF-β to active TGF-β; and (2) the therapeutic PDT dose interferes with this injury activation process. This study substantiates the concept of local cytokine inhibition by PDT in a biologic system and provides new insights into the mechanisms of PDT-mediated inhibition of experimental IH. (J Vasc Surg 1997;25:1033-43.

Focal Aortic Dissection With Significant Stenosis: A Rare Long Term Complication After TEVAR for Blunt Traumatic Aortic Injury in an Adolescent Patient

Background: Thoracic endovascular aortic repair (TEVAR) in children and adolescents after blunt traumatic aortic injury (BTAI) is being performed increasingly despite no endovascular graft being approved for TEVAR in this population. The smaller diameter of the aorta and access vessels and steeper angle of the aortic arch pose specific challenges for TEVAR in this population. Moreover, data are lacking regarding medium to long term complications. This case presents an adolescent patient who underwent TEVAR for BTAI and suffered a focal aortic dissection several months later. Report: The patient initially presented after a motor vehicle accident and underwent an uncomplicated TEVAR procedure with a 28 mm diameter stent graft (the smallest device available at the time) for Grade III traumatic aortic dissection; the native aortic diameter was 15 mm. The diameter mismatch was accepted due to the lifesaving nature of the procedure. More than 7 months later the patient presented to the emergency department after not being able to urinate for several days and experiencing pain, tingling, and weakness in both legs. Blood samples showed a severe acute kidney injury and computed tomography angiography showed significant aortic stenosis in the distal part of the stent graft, probably caused by a focal dissection. The stenosis and dissection were successfully treated using a Palmaz stent, after which his renal function and extremity complaints recovered. Conclusion: The focal dissection was probably caused by stress on the aortic wall due to the aorta–stent graft diameter mismatch. This case demonstrates that complications after TEVAR in adolescents can arise months after the initial procedure and underscores the need for continued vigilance, especially in cases with an aorta–stent graft mismatch. The threshold for additional imaging and consultation by a vascular surgeon should be low

A comparison of balloon injury models of endovascular lesions in rat arteries

Abstract Background Balloon injury (BI) of the rat carotid artery (CCA) is widely used to study intimal hyperplasia (IH) and decrease in lumen diameter (LD), but CCA's small diameter impedes the evaluation of endovascular therapies. Therefore, we validated BI in the aorta (AA) and iliac artery (CIA) to compare it with CCA. Methods Rats underwent BI or a sham procedure (control). Light microscopic evaluation was performed either directly or at 1, 2, 3, 4 and 16 weeks follow-up. The area of IH and the change in LD (LD at 16 weeks minus LD post BI) were compared. Results In the BI-groups the area of IH increased to 0.14 ± 0.08 mm2 (CCA), 0.14 ± 0.03 mm2 (CIA) and 0.12 ± 0.04 mm2 (AA) at 16 weeks (NS). The LD decreased with 0.49 ± 0.07 mm (CCA), compared to 0.22 ± 0.07 mm (CIA) and 0.07 ± 0.10 mm (AA) at 16 weeks (p Conclusions BI resulted in: (1.) a decrease in LD in CCA due to IH, (2.) a decrease in LD in CIA due to IH and CVR, (3.) no change in LD in AA, (4.) Comparable IH development in all arteries, (5.) CCA has no vasa vasorum compared to CIA and AA, (6.) The CIA model combines good access for 2 F endovascular catheters with a decrease in LD due to IH and CVR after BI.</p

Diabetes Mellitus Is Associated With Decreased Limb Survival in Patients With Critical Limb Ischemia : Pooled Data From Two Randomized Controlled Trials

OBJECTIVE: Although never assessed prospectively, diabetes mellitus (DM) is assumed to negatively affect the outcomes of critical limb ischemia (CLI). DM was highly prevalent in two recently conducted randomized controlled trials in CLI patients, the PADI (Percutaneous Transluminal Balloon Angioplasty [PTA] and Drug Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia) and JUVENTAS (Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-Arterial Supplementation) trials. To determine the implications of DM in a population of patients with infrapopliteal CLI, clinical outcomes were compared in patients with and without DM. RESEARCH DESIGN AND METHODS: Individual data from patients with CLI (Rutherford category ≥4) were pooled. Patients were considered to have DM when this diagnosis was reported in the hospital electronic medical records. Rates of major amputation (above ankle level) and major events (major amputation or death) were compared between CLI patients with and without DM. Hazard ratios (HRs) were calculated. RESULTS: Of a total of 281 patients, DM was present in 49.1%. The major amputation rate at 5 years of follow-up was higher in patients with DM than in patients without DM (34.1% vs. 20.4%, P = 0.015). The major event and death rate did not differ. The unadjusted HR of DM for the major amputation risk was 1.87 (95% CI 1.12-3.12). Model factors with significant HRs in the multivariate analysis were baseline Rutherford category (HR 1.95; 95% CI 1.24-3.06) and ankle-brachial index (ABI) >1.4 (HR 2.78; 95% CI 1.37-5.64). CONCLUSIONS: CLI patients with DM are at a significantly higher risk of major amputation than CLI patients without DM. This increased risk is associated with a higher prevalence of baseline ABI >1.4 and more severe ischemia at initial presentation in patients with DM