RESUMO
Thoracic aortic aneurysm (TAA) is an age-related and life-threatening vascular disease. Telomere shortening is a predictor of age-related diseases, and its progression is associated with premature vascular disease. The aim of the present work was to investigate the impacts of chronic hypoxia and telomeric DNA damage on cellular homeostasis and vascular degeneration of TAA. We analyzed healthy and aortic aneurysm specimens (215 samples) for telomere length (TL), chronic DNA damage, and resulting changes in cellular homeostasis, focusing on senescence and apoptosis. Compared with healthy thoracic aorta (HTA), patients with tricuspid aortic valve (TAV) showed telomere shortening with increasing TAA size, in contrast to genetically predisposed bicuspid aortic valve (BAV). In addition, TL was associated with chronic hypoxia and telomeric DNA damage and with the induction of senescence-associated secretory phenotype (SASP). TAA-TAV specimens showed a significant difference in SASP-marker expression of IL-6, NF-κB, mTOR, and cell-cycle regulators (γH2AX, Rb, p53, p21), compared to HTA and TAA-BAV. Furthermore, we observed an increase in CD163+ macrophages and a correlation between hypoxic DNA damage and the number of aortic telocytes. We conclude that chronic hypoxia is associated with telomeric DNA damage and the induction of SASP in a diseased aortic wall, promising a new therapeutic target.
Assuntos
Aneurisma da Aorta Torácica , Doença da Válvula Aórtica Bicúspide , Doenças das Valvas Cardíacas , Humanos , Doenças das Valvas Cardíacas/metabolismo , Fenótipo Secretor Associado à Senescência , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/complicações , Valva Aórtica/metabolismoRESUMO
A hallmark of thoracic aortic aneurysms (TAA) is the degenerative remodeling of aortic wall, which leads to progressive aortic dilatation and resulting in an increased risk for aortic dissection or rupture. Telocytes (TCs), a distinct type of interstitial cells described in many tissues and organs, were recently observed in the aortic wall, and studies showed the potential regulation of smooth muscle cell (SMC) homeostasis by TC-released shed vesicles. The purpose of the present work was to study the functions of TCs in medial degeneration of TAA. During aneurysmal formation an increase of aortic TCs was identified in human surgical specimens of TAA-patients, compared to healthy thoracic aortic (HTA)-tissue. We found the presence of epithelial progenitor cells in the adventitial layer, which showed increased infiltration in TAA samples. For functional analysis, HTA- and TAA-telocytes were isolated, characterized, and compared by their protein levels, mRNA- and miRNA-expression profiles. We detected TC and TC-released exosomes near SMCs. TAA-TC-exosomes showed a significant increase of the SMC-related dedifferentiation markers KLF-4-, VEGF-A-, and PDGF-A-protein levels, as well as miRNA-expression levels of miR-146a, miR-221 and miR-222. SMCs treated with TAA-TC-exosomes developed a dedifferentiation-phenotype. In conclusion, the study shows for the first time that TCs are involved in development of TAA and could play a crucial role in SMC phenotype switching by release of extracellular vesicles.
Assuntos
Aneurisma da Aorta Torácica , Exossomos , MicroRNAs , Telócitos , Aneurisma da Aorta Torácica/genética , Humanos , MicroRNAs/genética , Miócitos de Músculo LisoRESUMO
Background and Objectives: The feasibility of endovascular treatment (EVT) for Trans-Atlantic Inter-Society Consensus (TASC) II C and D femoropopliteal artery lesions has been described, but no prospective study has performed a long-term follow-up. The aim of this study was to report the long-term results of nitinol stents (NS) for the treatment of long femoropopliteal lesions. Materials and Methods: A single-center prospective, randomized controlled trial (RCT) comparing EVT with NS and vein bypass surgery was previously performed. The EVT group's follow-up was extended and separately analyzed with primary patency as the primary endpoint. The secondary endpoints were technical success, secondary patency, reinterventions, limb salvage, survival, complications, and clinical improvement. Results: Between 2016 and 2020, 109 limbs in 103 patients were included. A total of 48 TASC II C and 61 TASC II D lesions with a mean lesion length of 264 mm were reported. In 53% of limbs, the indication for treatment was chronic limb-threatening ischemia. The median follow-up was 45 months. Technical success was achieved in 88% of cases, despite 23% of the lesions being longer than 30 cm (retrograde popliteal access in 22%). At four-year follow-up, primary patency, secondary patency, and freedom from target lesion revascularizations were 35%, 48%, and 58%, respectively. Limb salvage and survival were 90% and 80% at 4 years. Clinical improvement of at least one Rutherford category at the end of follow-up was achieved in 83% of limbs. Conclusions: This study reports the longest follow-up of endovascular treatment with nitinol stents in femoropopliteal TASC II C and D lesions. The results emphasize the feasibility of an endovascular-first strategy, even in lesions beyond 30 cm in length, and clarify its acceptable long-term durability and good clinical outcomes. Large multicenter RCTs with mid- and long-term follow-up are needed to investigate the role of different endovascular techniques in long femoropopliteal lesions.
Assuntos
Procedimentos Endovasculares , Doença Arterial Periférica , Ligas , Consenso , Procedimentos Endovasculares/métodos , Humanos , Doença Arterial Periférica/cirurgia , Artéria Poplítea/cirurgia , Estudos Retrospectivos , Fatores de Risco , Stents , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
Telocytes (TCs), a novel interstitial cell entity promoting tissue regeneration, have been described in various tissues. Their role in inter-cellular signalling and tissue remodelling has been reported in almost all human tissues. This study hypothesizes that TC also contributes to tissue remodelling and regeneration of the human thoracic aorta (HTA). The understanding of tissue homeostasis and regenerative potential of the HTA is of high clinical interest as it plays a crucial role in pathogenesis from aortic dilatation to lethal dissection. Therefore, we obtained twenty-five aortic specimens of heart donors during transplantation. The presence of TCs was detected in different layers of aortic tissue and characterized by immunofluorescence and transmission electron microscopy. Further, we cultivated and isolated TCs in highly differentiated form identified by positive staining for CD34 and c-kit. Aortic-derived TC was characterized by the expression of PDGFR-α, PDGFR-ß, CD29/integrin ß-1 and αSMA and the stem cell markers Nanog and KLF-4. Moreover, TC exosomes were isolated and characterized for soluble angiogenic factors by Western blot. CD34+ /c-kit+ TCs shed exosomes containing the soluble factors VEGF-A, KLF-4 and PDGF-A. In summary, TC occurs in the aortic wall. Correspondingly, exosomes, derived from aortic TCs, contain vasculogenesis-relevant proteins. Understanding the regulation of TC-mediated aortic remodelling may be a crucial step towards designing strategies to promote aortic repair and prevent adverse remodelling.
Assuntos
Aorta/citologia , Exossomos/metabolismo , Expressão Gênica , Telócitos/citologia , Telócitos/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Biomarcadores , Micropartículas Derivadas de Células/metabolismo , Micropartículas Derivadas de Células/ultraestrutura , Exossomos/ultraestrutura , Fibroblastos/metabolismo , Imunofluorescência , Humanos , Imuno-Histoquímica , Imunofenotipagem , Fator 4 Semelhante a Kruppel/genética , Fator 4 Semelhante a Kruppel/metabolismo , Miócitos de Músculo Liso/metabolismo , Telócitos/ultraestrutura , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVES: Groin complications following vascular reconstruction, extensive trauma, or severe radiation induced scarring may complicate future revascularisation procedures of the lower limb. Although several techniques have been described, only few cases of trans-iliac bypass grafting have been published. The aim of this study was to perform a review of the literature on trans-ilac bypass grafting and add the authors' experience. METHODS: A single centre retrospective data analysis and a literature review of all trans-iliac bypass procedures was performed. Data on indication, patency, limb salvage, and survival were collected. Study endpoints were patency, limb salvage, and patient survival. RESULTS: Eight trans-iliac wing bypass grafting procedures were performed in our institution between 2003 and 2018, which represents the largest single centre series. Twenty-three procedures were reported in the literature between 1989 and 2018. Prior to the bypass procedure in the eight patients, six had local infection and two irradiation of the groin. The indication for operation was ischaemia in six cases, bleeding in one case, and infection in another case. The external iliac artery was most often used for the proximal (6 cases) and the superficial femoral artery for distal anastomosis (6 cases). Great saphenous vein was the most commonly used graft material (6 cases). The median follow up was five years with three bypass occlusions after 1, 2, and 8 months, followed by two successful thrombectomy procedures. There were no major amputations and only one death after five months, which was not procedure related. CONCLUSIONS: Trans-iliac bypass grafting is a viable alternative extra-anatomic bypass technique in patients with vascular groin complications. Patency as well as limb salvage and survival are good and may be comparable to those reported for autologous in situ repair and obturator canal bypass grafting.
Assuntos
Oclusão de Enxerto Vascular/epidemiologia , Virilha/irrigação sanguínea , Salvamento de Membro/métodos , Doenças Vasculares/cirurgia , Enxerto Vascular/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica/estatística & dados numéricos , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Feminino , Artéria Femoral/cirurgia , Seguimentos , Oclusão de Enxerto Vascular/etiologia , Virilha/cirurgia , Mortalidade Hospitalar , Humanos , Artéria Ilíaca/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Doenças Vasculares/etiologia , Doenças Vasculares/mortalidade , Enxerto Vascular/efeitos adversos , Grau de Desobstrução VascularRESUMO
Central processes in the pathogenesis of TAV- (tricuspid aortic valve) and BAV- (bicuspid aortic valve) associated ascending thoracic aortic aneurysm (ATAA) development are still unknown. To gain new insights, we have collected aortic tissue and isolated smooth muscle cells of aneurysmal tissue and subjected them to in situ and in vitro analyses. We analyzed aortic tissue from 78 patients (31 controls, 28 TAV-ATAAs, and 19 BAV-ATAAs) and established 30 primary smooth muscle cell cultures. Analyses included histochemistry, immuno-, auto-fluorescence-based image analyses, and cellular analyses including smooth muscle cell contraction studies. With regard to TAV associated aneurysms, we observed a strong impairment of the vascular wall, which appears on different levels-structure and dimension of the layers (reduced media thickness, increased intima thickness, atherosclerotic changes, degeneration of aortic media, decrease of collagen, and increase of elastic fiber free area) as well as on the cellular level (accumulation of fibroblasts/myofibroblasts, and increase in the number of smooth muscle cells with a reduced alpha smooth muscle actin (α-SM actin) content per cell). The pathological changes in the aortic wall of BAV patients were much less pronounced-apart from an increased expression of osteopontin (OPN) in the vascular wall which stem from smooth muscle cells, we observed a trend towards increased calcification of the aortic wall (increase significantly associated with age). These observations provide strong evidence for different pathological processes and different disease mechanisms to occur in BAV- and TAV-associated aneurysms.
Assuntos
Aneurisma da Aorta Torácica/etiologia , Aneurisma da Aorta Torácica/metabolismo , Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas/metabolismo , Doenças das Valvas Cardíacas/patologia , Osteopontina/metabolismo , Valva Tricúspide/metabolismo , Valva Tricúspide/patologia , Actinas/metabolismo , Adulto , Idoso , Aneurisma da Aorta Torácica/patologia , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Doença da Válvula Aórtica Bicúspide , Calcinose , Feminino , Fibroblastos/metabolismo , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/metabolismo , Osteopontina/genéticaRESUMO
OBJECTIVE: Technical progress in angioplasty expanded its application to very distal arterial lesions of the lower extremity. In cases of unsuccessful angioplasty tibiodistal bypass surgery may be required for limb salvage. We investigated the long-term outcome of this technique in patients with critical limb ischemia. The purpose of this study was to evaluate whether tibiodistal bypasses done after unsuccessful tibial angioplasty had inferior patency, limb salvage, or survival rates compared with primary tibiodistal bypasses. METHODS: This single-center, retrospective data analysis included all distal bypass procedures originating from a tibial artery. Primary study end points were primary patency, secondary patency, and limb salvage. Secondary end points included survival, wound healing, and systemic and local complications. Society for Vascular Surgery reporting standards were applied. RESULTS: There were 61 tibiodistal vein bypasses for critical limb ischemia performed in 23 years. Indications for tibiodistal bypass was Rutherford category 5 in 41 cases (67%) and category 6 in 20 cases (33%). Procedures were allocated to group A (primary bypass; n = 28) and group B (bypass after unsuccessful tibial angioplasty; n = 33). Primary patency was 55% versus 53% at 1 year and 47% versus 44% at 3 years (P = .58). Secondary patency was 59% versus 64% at 1 year and 52% versus 55% at 3 years (P = .36). Limb salvage was 96% versus 90% at 1 year and 91% versus 85% at 3 years (P = .44). Overall survival rates were 91% versus 97% at 1 year and 85% versus 92% at 3 years (P = .76). The median follow-up was 4.0 years in group A and 4.9 years in group B. In multivariate analyses for loss of primary patency and limb loss, no significant predictors could be identified. CONCLUSIONS: This study showed that tibiodistal vein bypass is a feasible, efficient, and safe technique in patients with critical limb ischemia. It provides acceptable primary and secondary patency rates to prevent major amputation and ensure survival. Previous unsuccessful tibial angioplasty had no significant impact on tibiodistal vein bypass outcome. This technique should be part of the armamentarium of vascular surgeons.
Assuntos
Angioplastia/efeitos adversos , Isquemia/terapia , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/terapia , Artérias da Tíbia/cirurgia , Enxerto Vascular/métodos , Veias/transplante , Idoso , Idoso de 80 Anos ou mais , Angioplastia/mortalidade , Áustria , Estado Terminal , Feminino , Humanos , Isquemia/diagnóstico por imagem , Isquemia/mortalidade , Isquemia/fisiopatologia , Estimativa de Kaplan-Meier , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Artérias da Tíbia/diagnóstico por imagem , Artérias da Tíbia/fisiopatologia , Fatores de Tempo , Enxerto Vascular/efeitos adversos , Enxerto Vascular/mortalidade , Grau de Desobstrução Vascular , CicatrizaçãoRESUMO
Ascending aortic aneurysms are mostly asymptomatic and present a great risk of aortic dissection or perforation. Consequently, ascending aortic aneurysms are a source of lethality with increased age. Biological aging results in progressive attrition of telomeres, which are the repetitive DNA sequences at the end of chromosomes. These telomeres play an important role in protection of genomic DNA from end-to-end fusions. Telomere maintenance and telomere attrition-associated senescence of endothelial and smooth muscle cells have been indicated to be part of the pathogenesis of degenerative vascular diseases. This systematic review provides an overview of telomeres, telomere-associated proteins and telomerase to the formation and progression of aneurysms of the thoracic ascending aorta. A better understanding of telomere regulation in the vascular pathology might provide new therapeutic approaches. Measurements of telomere length and telomerase activity could be potential prognostic biomarkers for increased risk of death in elderly patients suffering from an aortic aneurysm.
Assuntos
Envelhecimento/metabolismo , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/patologia , Encurtamento do Telômero , Telômero/metabolismo , Animais , Biomarcadores/metabolismo , DNA/metabolismo , Humanos , Camundongos , Ratos , Fatores de Risco , Telomerase/metabolismo , Telômero/genéticaRESUMO
BACKGROUND: The timing of treatment for chronic aortic valve regurgitation (AR), especially in asymptomatic patients, is gaining attention since less invasive strategies have become available. The aim of the present study was to evaluate left ventricular reverse remodeling after aortic valve replacement (AVR) for severe AR. METHODS: Patients (n = 25) who underwent surgical AVR for severe AR with left ventricular ejection fraction (LVEF) less than 55% were included in this study. Preprocedural and follow-up clinical and echocardiographic measurements of LVEF and left ventricular (LV) diameters were retrospectively analyzed. RESULTS: Mean LVEF increased significantly following surgical AVR (p < 0.0001). LV diameters showed a clear regression (p = 0.0088). Younger patients and those receiving a mechanical valve tended to have less improved LVEF on follow-up than patients over 60 years or the ones who were implanted with a biological prosthesis (p = 0.0239 and p = 0.069, respectively). Gender had no effect on the degree of LVEF improvement (p = 0.4908). CONCLUSIONS: We demonstrated significant LV reverse remodeling following AVR for AR. However, more data are needed on LV functional and geometrical improvement comparing the different types of valve prostheses to provide an optimal treatment strategy.
RESUMO
OBJECTIVES: The objective of this study was to enhance the efficiency of aortic arch replacement through the development of a novel frozen elephant trunk (FET) prosthesis with an endovascular side branch for left subclavian artery (LSA) connection. After successful pre-clinical testing, the feasibility and safety of implementing this innovative prosthesis in human subjects were investigated. METHODS: Between September 2020 and September 2021, 4 patients (mean age 67) with conditions such as penetrating ulcer, non A-non B aortic dissection and chronic arch aneurysm underwent surgery utilizing the customized device. Surgeries were performed under high moderate hypothermia (27°C), employing bilateral selective antegrade cerebral perfusion (SACP) and distal aortic perfusion. Anastomosis of the FET prosthesis with the aortic arch occurred in zone 1, followed by separate reimplantation of the left common carotid artery and the brachiocephalic artery. RESULTS: All patients were discharged in good clinical condition. The mean aortic cross-clamp, antegrade selective cerebral perfusion and distal aortic perfusion times were 111, 71 and 31 min, respectively. Endovascular extension of the side branch for the LSA was required in all cases to prevent endoleak formation. One patient received a stent graft extension at the end of the operation, while 2 others underwent the procedure during their hospital stay. One patient was diagnosed with an endoleak at the first follow-up after 3 months, and endoleak sealing was achieved via the brachial artery with an extension stent graft. CONCLUSIONS: Preliminary clinical outcomes suggest that the newly designed FET prosthesis shows promise in simplifying total arch replacement. These initial findings provide a foundation for planned clinical studies to further assess the effectiveness of this modified surgical hybrid graft, with particular attention to the length and diameter of the LSA sidearm.
Assuntos
Implante de Prótese Vascular , Prótese Vascular , Procedimentos Endovasculares , Artéria Subclávia , Humanos , Artéria Subclávia/cirurgia , Idoso , Masculino , Implante de Prótese Vascular/métodos , Implante de Prótese Vascular/instrumentação , Implante de Prótese Vascular/efeitos adversos , Pessoa de Meia-Idade , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/instrumentação , Dissecção Aórtica/cirurgia , Desenho de Prótese , Aneurisma da Aorta Torácica/cirurgia , Feminino , Aorta Torácica/cirurgiaRESUMO
Objective: Cardiac surgery is known to activate a cascade of inflammatory mediators leading to a systemic inflammatory response. Hemadsorption (HA) devices such as CytoSorb® have been postulated to mitigate an overshooting immune response, which is associated with increased morbidity and mortality, and thus improve outcome. We aimed to investigate the effect of CytoSorb® on interleukin (IL)-6 levels in patients undergoing complex cardiac surgery in comparison to a control group. Methods: A total of 56 patients (28 CytoSorb®, 28 control) undergoing acute and elective cardiac surgery between January 2020 and February 2021 at the Department of Cardiac and Vascular Surgery, Clinic Floridsdorf, Vienna, were retrospectively analyzed. The primary endpoint was the difference in IL-6 levels between the CytoSorb® and control group. Secondary endpoint was periprocedural mortality. Results: CytoSorb®, installed in the bypass circuit, had no significant effect on IL-6 levels. IL-6 peaked on the first postoperative day (HA: 775.3 ± 838.4 vs. control: 855.5 ± 1,052.9â pg/ml, p = 0.856). In total, three patients died in the HA group, none in the control (logistic regression model, p = 0.996). Patients with an increased Euroscore II of 7 or more showed a reduced IL-6 response compared to patients with an Euroscore II below 7 (178.3 ± 63.1â pg/ml vs. 908.6 ± 972.6â pg/ml, p-value = 0.00306). Conclusions: No significant reduction of IL-6 levels or periprocedural mortality through intraoperative HA with CytoSorb® in patients undergoing cardiac surgery was observed. However, this study was able to show a reduced immunologic response in patients with a high Euroscore II. The routine application of CytoSorb® in cardiac surgery to reduce inflammatory mediators has to be scrutinized in future prospective randomized studies.
RESUMO
The frozen elephant trunk (FET) technique is an established therapeutic option in the treatment of complex aortic diseases. We report our long-term clinical outcomes after FET repair. A total of 187 consecutive patients underwent FET repair at our department between 8/2005 and 3/2023. Indications included acute and chronic aortic dissections and thoracic aneurysms. Endpoints included operative morbidity and mortality, long-term survival, and the need for reinterventions. Operative mortality, spinal cord injury and permanent stroke rates were: 9.6%, 2.7% and 10.2%, respectively. At five years, overall survival was 69.9 ± 3.9% and freedom from aortic-related death was 82.5 ± 3.0%, whereas at ten years, overall survival was 53.0 ± 5.5% and freedom from aortic-related death was 75.8 ± 4.8%. Sixty-one reinterventions on the thoracic aorta were necessary. Freedom from secondary interventions at ten years was 44.7 ± 6.4% overall (63.1 ± 10.0% for acute dissections, 40.8 ± 10.3% for chronic dissections and 28.9 ± 13.1% for aneurysms, respectively). The high reintervention rate for chronic dissections and for aneurysms is related to the pre-existing aortic pathology. Late aortic growth of untreated segments with potentially fatal outcome occurs even after ten years, so careful annual follow-up is mandatory in this patient cohort.
RESUMO
Background: During on-pump coronary artery bypass grafting (ONCAB), graft flushing for distal anastomoses testing also perfuses the downstream myocardium. This single-center retrospective study evaluated the impact of specific preservation solutions on myocardial protection during ONCAB. Materials and methods: Between July 2019 and March 2020 either DuraGraft (DG) or 0.9% Saline/Biseko (SB) was applied to 272 ONCAB. Overall, 166 patients were propensity-matched into two groups. Cardiac enzymes [high-sensitive Troponin I (hs-TnI) and creatine kinase (CK)] were evaluated 7 days post-surgery. Results: Post-surgery, hs-TnI values were significantly lower from 3 to 6 h (h) up to 4 days in the DG group: 3-6 h: 4,034 ng/L [IQR 1,853-8,654] vs. 5,532 ng/L [IQR 3,633-8,862], p = 0.05; 12-24 h: 2,420 ng/L [IQR 1,408-5,782] vs. 4,166 [IQR 2,052-8,624], p < 0.01; 2 days: 1,095 ng/L [IQR 479-2,311] vs. 1,564 ng/L [IQR 659-5,057], p = 0.02 and at 4 days: 488 ng/L [IQR 232-1,061] vs. 745 ng/L [IQR 319-1,820], p = 0.03. The maximum value: 4,151 ng/L [IQR 2,056-8,621] vs. 6,349 ng/L [IQR 4,061-12,664], p < 0.01 and the median area under the curve (AUC): 6,146 ng/L/24 h [IQR 3,121-13,248] vs. 10,735 ng/L/24 h [IQR 4,859-21,484], p = 0.02 were lower in the DG group. CK values were not significantly different between groups: maximum value 690 [IQR 417-947] vs. 631 [464-979], p = 0.61 and AUC 1,986 [1,226-2,899] vs. 2,081 [1,311-3,063], p = 0.37. Conclusion: Repeated graft flushing with DG resulted in lower Troponin values post-surgery suggesting enhanced myocardial protection compared to SB. Additional studies are warranted to further assess the myocardial protection properties of DG.
RESUMO
The radial artery (RA) is a frequently used conduit in coronary artery bypass grafting (CABG). Endothelial injury incurred during graft harvesting promotes oxidative damage, which leads to graft disease and graft failure. We evaluated the protective effect of DuraGraft®, an endothelial damage inhibitor (EDI), on RA grafts. We further compared the protective effect of the EDI between RA grafts and saphenous vein grafts (SVG). Samples of RA (n = 10) and SVG (n = 13) from 23 patients undergoing CABG were flushed and preserved with either EDI or heparinized Ringer's lactate solution (RL). The effect of EDI vs. RL on endothelial damage was evaluated ex vivo and in vitro using histological analysis, immunofluorescence staining, Western blot, and scanning electron microscopy. EDI-treated RA grafts showed a significant reduction of endothelial and sub-endothelial damage. Lower level of reactive oxygen species (ROS) after EDI treatment was correlated with a reduction of hypoxic damage (eNOS and Caveolin-1) and significant increase of oxidation-reduction potential. Additionally, an increased expression of TGFß, PDGFα/ß, and HO-1 which are indicative for vascular protective function were observed after EDI exposure. EDI treatment preserves functionality and integrity of endothelial and intimal cells. Therefore, EDI may have the potential to reduce the occurrence of graft disease and failure in RA grafts in patients undergoing CABG.
RESUMO
The saphenous vein graft (SVG) remains the most commonly used conduit in coronary artery bypass grafting (CABG). In light of this further research must be aimed at the development of strategies to optimize SVG patency and thereby improve both short- and long-term outcomes of CABG surgery. SVG patency in large part depends on the protection of the structural and functional integrity of the vascular endothelium at the time of conduit harvesting, including optimal storage conditions to prevent endothelial damage. This review provides an overview of currently available storage and preservation solutions, including novel endothelial damage inhibitors, and their role in mitigating endothelial damage and vein graft failure.
Assuntos
Prótese Vascular , Ponte de Artéria Coronária , Endotélio Vascular/patologia , Veia Safena , Grau de Desobstrução Vascular , HumanosRESUMO
The Berlin Heart EXCOR® is a mechanical, pulsatile ventricular assist device. The paracorporeal assist device is pneumatically driven and can be used for long-term bridging therapy of one or both ventricles (LVAD, BIVAD, RVAD). It is specifically designed for pediatric patients and can be used in neonates as well as juveniles and adults. The infant presented in this video tutorial was diagnosed with myocarditis leading to end-stage heart failure and severe mitral valve regurgitation. A bridging therapy was indicated and a Berlin Heart EXCOR® VAD was implanted. This tutorial provides detailed insight on how to perform this procedure. In addition, a safe and effective way of extending the outflow cannula is demonstrated.
Assuntos
Insuficiência Cardíaca/cirurgia , Coração Auxiliar , Implantação de Prótese/métodos , Insuficiência Cardíaca/fisiopatologia , Humanos , LactenteRESUMO
The Melody valve (Medtronic, Minneapolis, MN, USA) is a stented bovine jugular vein graft that was primarily approved for transcatheter implantation in a pulmonary valve position. The prosthetic valve can also be implanted in an atrioventricular position in infants and young children, and in these cases it must be modified appropriately. In this tutorial we demonstrate the surgical preparation of a stented transcatheter Melody valve for implantation in the atrioventricular position. Additionally, we present a safe and effective method for surgical valve-in-valve implantation in a 3-year-old patient with hypoplastic left heart syndrome.
Assuntos
Bioprótese , Implante de Prótese de Valva Cardíaca/métodos , Próteses Valvulares Cardíacas , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Stents , Animais , Bovinos , Humanos , Lactente , Veias Jugulares/cirurgia , Valva Tricúspide/cirurgiaRESUMO
The implantation of a decellularized aortic homograft in children and young adults has been shown to be a good alternative to existing surgical approaches. Lower risk of calcification and the potential of growth render a homograft a promising valve substitute. The child presented in this video tutorial is a 10-year-old boy diagnosed with congenital aortic stenosis which was treated by balloon valvuloplasty early in life. Current echocardiographic findings show severe aortic regurgitation and stenosis. The tutorial provides detailed insight into how to implant a decellularized aortic homograft as a total root replacement.
Assuntos
Insuficiência da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/congênito , Estenose da Valva Aórtica/cirurgia , Valva Aórtica/transplante , Valvuloplastia com Balão , Aloenxertos , Insuficiência da Valva Aórtica/etiologia , Criança , Ecocardiografia , Humanos , Masculino , Transplante HomólogoRESUMO
Malignant cells ensure telomere maintenance by the alternative lengthening of telomeres (ALT) in the absence of telomerase activity (TA). The retrotransposons "long interspersed nuclear element-1" (LINE-1, L1) are expressed in malignant cells and are primarily known to contribute to complex karyotypes. Here we demonstrate that LINE-1 ribonucleoprotein particles (L1-RNPs) expression is significantly higher in ALT+- versus in TA+-human glioma. Analyzing a role of L1-RNP in ALT, we show that L1-RNPs bind to telomeric repeat containing RNA (TERRA), which is critical for telomere stabilization and which is overexpressed in ALT+ cells. In turn, L1-RNP knockdown (KD) abrogated the nuclear retention of TERRA, resulted in increased telomeric DNA damage, decreased cell growth and reduced expression of ALT characteristics such as c-circles and PML-bodies. L1-RNP KD also decreased the expression of Shelterin- and the ALT-regulating protein Topoisomerase IIIα (TopoIIIα) indicating a more general role of L1-RNPs in supporting telomeric integrity in ALT. Our findings suggest an impact of L1-RNP on telomere stability in ALT+ dependent tumor cells. As L1-RNPs are rarely expressed in normal adult human tissue those elements might serve as a novel target for tumor ablative therapy.
Assuntos
DNA Topoisomerases Tipo I/genética , Proteínas de Ligação a DNA/genética , Glioma/genética , Telômero/genética , Fatores de Transcrição/genética , Linhagem Celular Tumoral , Dano ao DNA/genética , Glioma/patologia , Humanos , Elementos Nucleotídeos Longos e Dispersos/genética , Ribonucleoproteínas/genética , Homeostase do Telômero/genéticaRESUMO
Pathological impairment of elastic fiber and other extracellular matrix (ECM) components are described for the aortic media of ascending thoracic aortic aneurysms (aTAA) but the exact pathological impairment of the structure and its degree still needs further investigations. To evaluate the quantity and quality of elastic fiber sheets and other ECM structures (e.g. collagen), cells were removed from different types of aneurysmal tissues (tricuspid aortic valve [TAV] associated-, bicuspid aortic valve [BAV] associated-aneurysmal tissue and acute aortic dissections [AAD]) using 2.5% sodium hydroxide (NaOH) and compared to decellularized control aortic tissue. Likewise, native tissue has been analysed. To evaluate the 2D- (histological evaluation, fluorescence- and auto-fluorescence based staining methods) and the 3D structure (scanning electron microscopic [SEM] examination) of the medial layer we first analysed for a successful decellularization. After proving for successful decellularization, we quantified the amount of elastic fiber sheets, elastin and other ECM components including collagen. Aside from clearly visible focal elastic fiber loss in TAV-aTAA tissue, decellularization resulted in reduction of elastic fiber auto-fluorescence properties, which is perhaps an indication from a disease-related qualitative impairment of elastic fibers, visible only after contact with the alkaline solution. Likewise, the loss of collagen amount in BAV-aTAA and TAV-aTAA tissue (compared to non-decellularized tissue) after contact with NaOH indicates a prior disease-associated impairment of collagen. Although the amount of ECM was not changed in type A dissection tissue, detailed electron microscopic evaluation revealed changes in ECM quality, which worsened after contact with alkaline solution but were not visible after histological analyses. Apart from the improved observation of the samples using electron microscopy, contact of aneurysmal and dissected tissue with the alkaline decellularization solution revealed potential disease related changes in ECM quality which can partly be connected to already published data, but have to be proven by further studies.