Aortic Segments Research Articles

Dynamic Morphology of Dilated Ascending Aorta and its Implications for Proximal Landing During Thoracic Endovascular Aortic Repair

Introduction: To improve the outcomes of thoracic endovascular aortic repair (TEVAR), we investigated the dynamic morphology of dilated and nondilated ascending aortas (AAs) to determine whether an appropriate proximal landing zone for TEVAR exists if the middle AA is dilated. Materials and Methods: Patients with dilated (diameter 40–50 mm) and nondilated (<40 mm) AAs underwent electrocardiogram-gated computed tomography angiography of the entire AA in the systolic and diastolic phases. For each plane of each AA segment, the maximal and minimal diameters in systole and diastole were recorded. Results: A total of 105 patients were enrolled (54% male; median age: 80 years [IQR 78–85]). A total of 35 patients were included in the dilated AA group (DG), and 70 patients were included in the nondilated AA group (n-DG). The aortic planes of the AA segment at the sinotubular junction (STJ) showed a more oval-shaped morphology compared with the distal planes of the same segment (the differences between the maximum and minimum diameters were 8.9% to 9.4% and 4.8% to 5.6%, respectively). If the mid-ascending aorta was dilated, the aortic segment at the STJ showed a more pronounced reversed-funnel 3D morphology, with a 14% (IQR 11%–19%) difference in diameters between the proximal and distal segmental planes shown in the n-DG and 18% (IQR 16%–22%, p<0.001) in the DG. Conclusion: If the middle AA is dilated, it is considered unsuitable to perform TEVAR using conventional endografts without additional proximal fixation in the aortic segment at the STJ due to its pronounced reversed-funnel segmental morphology. By contrast, the aortic segment at the brachiocephalic trunk seems to be promising for performing TEVAR using an endograft of the appropriate size and conformability. Moreover, endograft sizing using the average aortic diameter instead of the maximal AA diameter in an oval-shaped aortic plane morphology should be considered. Clinical Impact If the middle ascending aorta is dilated, it is considered unsuitable to perform TEVAR with a proximal landing in the aortic segment at the sinotubular junction due to its pronounced reversed-funnel segmental morphology and high risk of type Ia endoleak and endograft migration. By contrast, the aortic segment at the brachiocephalic trunk seems to be promising for performing TEVAR due to its moderate funnel morphology using an endograft of appropriate size and conformability.

Enhanced Vasoconstriction in Sickle Cell Disease is Dependent on ETA Receptor Activation

Sickle Cell Disease (SCD) carries a significant risk for poor vascular health and vascular dysfunction. High levels of vascular reactive oxygen species (ROS) as well as elevated plasma endothelin-1 (ET-1), a potent vasoconstrictor with actions via the ETA receptor, are both common phenotypes in SCD. Alpha-1 adrenergic receptor activation is a major mediator of stress-induced vasoconstriction. However, the mechanism of the SCD enhanced vasoconstrictive response is unknown. We hypothesized that SCD induces enhanced alpha-1 adrenergic mediated vasoconstriction through the ET-1/ETA receptor pathway in arterial tissues. Utilizing humanized SCD (HbSS) and genetic control (HbAA) mice, alpha-1a, but not alpha-1b or alpha-1d, receptor expression was significantly greater in aortic tissue from HbSS mice compared to HbAA mice. Significantly enhanced vasoconstriction in aortic and carotid arterial segments were observed from HbSS mice compared to HbAA mice. Treatment with ambrisentan, a selective ETA receptor antagonist, and a ROS scavenger normalized the aortic vasoconstrictive response in HbSS mice. In a randomized translational study, patients with SCD were treated with placebo or ambrisentan for 3 months, with the treatment group showing an increase in the percent brachial arterial diameter. Taken together, these data suggest that the ETA receptor pathway interaction with the adrenergic receptor pathway contributes to enhanced aortic vasoconstriction in SCD. Findings indicate the potential of ETA antagonism as a therapeutic avenue for improving vascular health in SCD.

PI 3-kinase/AKT/FOXO1 signaling in smooth muscle cells protects against abdominal aortic aneurysm

Abstract Background Abdominal aortic aneurysms (AAA) are characterized by loss of vascular smooth muscle cells (SMCs). Growth factors induce proliferation and cell survival of SMCs. PI 3-kinase (PI3K) is an important downstream mediator in growth factor signaling. Objective This project is based on the hypothesis that PI3K-mediated SMC proliferation can compensate for the loss of SMCs in AAA and thus inhibit AAA progression. Therefore, we determined effects of reduced PI3K activity in SMCs on AAA progression, cell proliferation as well as vascular remodeling. Methods To investigate the role of PI3K, we analyzed mice and aortic SMCs harboring a smooth muscle-specific deficiency of the PI3K catalytic subunit p110α (SM-p110α-/-). AAA development in SM-p110α-/- mice and wild-type (WT) littermates was induced by perfusion of the infrarenal aortic segment with porcine pancreatic elastase (PPE). AAA diameter was determined by echocardiography. Structural changes in the aorta were identified by (immuno)histochemical staining. SMC proliferation was measured in vitro by BrdU incorporation or real-time cell analysis. p110α induced signal transduction pathways were characterized by Western blot and transcriptome analysis. Results PPE treatment led to a massive loss of SMCs in the compromised aortic segment after 3 days in both SM-p110α-/- and WT mice. The aortic diameter was enlarged after 28 days in all PPE-treated mice. However, the increase was significantly higher in SM-p110α-/- mice (70.2±10.8%, n=9) compared to WT animals (42.4±6.0%, n=10) (p<0.05). A similar effect was obtained in aged (untreated) mice: In 24-month-old SM-p110α-/- mice, abdominal aortic lumen diameter was increased by 42% compared to 3-month-old animals, but only by 15% in corresponding WT mice. PPE-treated SM-p110α-/- mice were characterized by reduced vascular remodeling with less PCNA-positive proliferating cells compared to WT animals. In addition, proliferation of aortic p110α-/- SMCs in serum-containing medium was impaired. Mechanistic analyses showed that PDGF- and insulin-induced activation of AKT as well as AKT-dependent phosphorylation and inactivation of the transcription factors FOXO-1, -3 and -4 were significantly reduced in p110α-/- SMCs compared to WT cells. Further analyses revealed that specific inhibition of FOXO1 by AS1842856 rescued PDGF or serum stimulated proliferation of p110α-/- SMCs. In addition, expression analysis of FOXOs in patients revealed significantly increased FOXO1 expression in AAA compared to aortic samples from healthy individuals. Conclusion Deficiency of the catalytic PI3K isoform p110α in SMCs promotes the development and progression of AAA. p110α/AKT-dependent inactivation of FOXO1 induces SMC proliferation, which can ameliorate aortic wall damage. As FOXO1 inhibitors and a recently developed p110α activator are available, the PI3K/AKT/FOXO1 signaling cascade may provide a therapeutic target to influence the stability of the aortic wall in AAA.

Impact of protruding and ulcerated aortic atheroma on periprocedural ischemic stroke in patients undergoing transcatheter aortic valve replacement: a comprehensive analysis

Abstract Backgrounds Aortic atherosclerosis has the potential to impact both the strategy and outcomes of transcatheter aortic valve replacement (TAVR). Past research has established a correlation between the thickness and volume of aortic atheroma with periprocedural ischemic stroke and long-term mortality. However, there is limited investigation into the relationship between the morphology of aortic atheroma and outcomes following TAVR. Purpose The study aimed to assess the influence of protruding and ulcerated aortic atheroma on the occurrence of periprocedural ischemic stroke following TAVR. Methods A total of 979 patients who underwent TAVR between February 2012 and May 2019, and had retrospectively available data from contrast-enhanced computed tomography, were included in this analysis. The presence of protruding or ulcerated atheroma was evaluated across four aortic segments: ascending aorta, aortic arch, descending aorta, and abdominal aorta. Protruding aortic atheroma was defined as atheroma with a thickness exceeding 3 mm and protruding components. Ulcerated aortic atheroma was defined as atheroma presenting with ulcer-like disruption of the intima. The primary endpoint assessed was periprocedural ischemic stroke occurring within 48 hours following TAVR. Results The frequencies of protruding and ulcerated aortic atheroma were as follows: 0.2% in the ascending aorta, 6.5% in the aortic arch, 11.1% in the descending aorta, 15.7% in the abdominal aorta, and 24.2% in the entire aorta (Figure 1). Among the 979 patients analyzed, 25 (2.6%) experienced periprocedural ischemic stroke. Patients with protruding or ulcerated aortic atheroma exhibited a significantly higher incidence of periprocedural ischemic stroke compared to those without (5.5% vs. 1.6%, p=0.0010). Multivariate logistic analysis revealed that protruding or ulcerated aortic atheroma, particularly in the aortic arch, independently increased the risk of periprocedural ischemic stroke. (Table 1). Among the subset of patients (309, 34%) undergoing transfemoral TAVR (TF-TAVR) with a self-expandable valve, those with protruding or ulcerated aortic atheroma had a notably higher incidence of periprocedural ischemic stroke compared to those without (9.6% vs. 1.6%, p=0.0083). Conversely, among patients (587, 66%) undergoing TF-TAVR with a balloon-expandable valve, there was no statistically significant difference in the incidence of periprocedural ischemic stroke between those with and without protruding or ulcerated aortic atheroma (4.2% vs. 1.8%, p=0.102). Conclusions Protruding and ulcerated aortic atheroma, particularly in the aortic arch, were linked to a higher risk of periprocedural ischemic stroke post-TAVR. Consequently, careful selection of TAVR strategy, including valve type and procedural approach, is essential for patients with such aortic lesions.Figure 1Table 1

On the Relative Effects of Wall and Intraluminal Thrombus Constitutive Material Properties in Abdominal Aortic Aneurysm Wall Stress.

An abdominal aortic aneurysm (AAA) is a dilation localized in the infrarenal segment of the abdominal aorta that can expand continuously and rupture if left untreated. Computational methods such as finite element analysis (FEA) are widely used with in silico models to calculate biomechanical predictors of rupture risk while choosing constitutive material properties for the AAA wall and intraluminal thrombus (ILT). In the present work, we investigated the effect of different constitutive material properties for the wall and ILT on 21 idealized and 10 unruptured patient-specific AAA geometries. Three material properties were used to characterize the wall and two for the ILT, leading to six material model combinations for each AAA geometry subject to appropriate boundary conditions. The results of the FEA simulations indicate significant differences in the average peak wall stress (PWS), 99th percentile wall stress (99th WS), and spatially averaged wall stress (SAWS) for all AAA geometries subject to the choice of a material model combination. Specifically, using a material model combination with a compliant ILT yielded statistically higher wall stresses compared to using a stiff ILT, irrespective of the constitutive equation used to model the AAA wall. This work provides quantitative insight into the variability of the wall stress distributions ensuing from AAA FEA modeling due to its strong dependency on population-averaged soft tissue material characterizations. This dependency leads to uncertainty about the true biomechanical state of stress of an individual AAA and the subsequent assessment of its rupture risk.

Relationship between 3-dimensional aortic geometry and the risk of new-onset heart failure

Abstract Introduction Aortic geometric assessments to date have typically involved cross-sectional imaging of discrete aortic segments. However, the complex 3D geometry of the thoracic aorta, and its relationship to the risk of cardiovascular disease has not been assessed in large studies. Methods We segmented the thoracic aorta in SSFP axial MRI images from 49,282 UK Biobank participants using a deep convolutional neural network (U-Net). We then computed geometric measurements (centerline length, arch height, arch width, arch height-width ratio, arch unfolding index [inverse of tortuosity], curvature and mean, minimum and maximum diameters) in the overall thoracic aorta as well as in 6 subsegments. We quantified their relationship to the risk of cardiomyopathy and heart failure (HF) using multivariable Cox-proportional hazards models. All hazard ratios are standardized. Centerline length was allometrically indexed to body height. Results In models adjusted for age, sex, BMI kg/m2, low-density lipoprotein mg/dl, high-density lipoprotein mg/dl, triglycerides mg/dl, systolic blood pressure and diastolic blood pressure, the curvature of the aorta (HR=0.63; 95% CI=0.39, 0.99; P<0.05), particularly the aortic arch (HR=0.54; 95% CI= 0.35, 0.87; P<0.05) was strongly related to a lower risk of incident cardiomyopathy. A higher arch unfolding index (HR=1.46; 95% CI=1.03, 2.07; P<0.05), higher width-to-height ratio (HR=1.10; 95% CI= 1.02, 1.19; P<0.05) and lower aorta tortuosity (HR=1.20; 95% CI= 1.09, 1.32; P<0.05) were all associated with a higher risk of cardiomyopathy. This aortic geometric pattern was also associated with a greater risk of a new HF diagnosis (arch unfolding [HR=1.23; 95% CI= 1.07, 1.42; P<0.05], width to heigh ratio [HR=1.06; 95% CI= 1.01, 1.11; P0.05]). Conclusion We demonstrate that 3-D thoracic aortic geometric indices are strongly associated with incident cardiomyopathy and HF, independent of classic risk factors. This is likely related to abnormal afterload and ventricular-arterial interactions since adverse geometric remodeling affects left ventricular pulsatile load.Cardiomyopathy & Heart Failure Hazards

Conditional over-expression of heme-oxygenase 1 in myelomonocytic cells reduces AngII-induced hypertension and vascular inflammation in mice

Abstract Background Systemic arterial Hypertension is one of the most important risk factor responsible for morbidity and mortality world-wide. Angiotensin II (Ang II), a potent vasoconstrictor and key player in the renin-angiotensin-aldosterone system (RAAS) is responsible for vascular dysfunction, inflammation, and tissue damage. Heme oxygenase-1 (HO-1) overexpression may confer antioxidant and anti-inflammatory properties in Ang II-induced hypertension through its action on heme catabolism, generating carbon monoxide (CO), ferritin and biliverdin/bilirubin by the action of biliverdin reductase A (BLVRA). Methods and results Male 9–12-weeks-old HO-1indxLySMCre/wt and LySMCre/wt mice were infused with AngII (1mgAngII/Day/Kg) for 7 days to induce hypertension and compared to sham treatment. Blood pressure monitoring by tail-cuff method, and endothelium-dependent vasodilator studies via organ chamber system using acetylcholine (ACh) in isolated aortic segments (~4 mm), revealed that overexpression of HO-1 in myeloid cells resulted in decreased systolic blood pressure and improved endothelial function in AngII-infused HO-1indxLySMCre/wt mice compared to controls. Concurrently, increased BLVRA expression in liver tissue and elevated plasma bilirubin levels were detected by transcriptome analysis and high-performance liquid chromatography, respectively. These results were supported by a reduction in the expression of inducible cytokines and cell adhesion molecules (CAMs) in the aorta, assessed using qPCR. Bone marrow transplant experiments demonstrated that bone marrow from LysMcre mice in HO-1indxLySMCre/wt mice abrogated the protective effect of HO-1, resulting in endothelial damage and increased blood pressure, potentially due to decreased liver BLVRA expression and the accumulation of bone marrow-derived cells in the vessel wall in response to AngII. Additionally, adeno-associated viral vector (AAV) transfection targeting specifically BLVRA activity in liver lead to an increase in blood pressure values and worse endothelium relaxation, in parallel with higher oxidative stress and the blood neutrophils concentration, as assessed in whole blood by using oxidative burst method and blood count system respectively. Conclusion The overexpression of HO-1 in myeloid cells confers anti-inflammatory protection in AngII-induced arterial hypertension in mice. Myeloid cells bone marrow-derived overexpressing HO-1 regulate the differentiation and infiltration of pro-inflammatory immune cells in the vasculature. BLVRA expression and bilirubin levels downstream of HO-1 play a critical role in protecting against vascular damage by reducing leukocyte infiltration.

Long-Term Outcomes of PETTICOAT Technique-Assisted Thoracic Endovascular Aortic Repair for the Treatment of Acute and Subacute Complicated Type B Aortic Dissection.

To evaluate the long-term outcomes of the provisional extension to induce complete attachment technique (PETTICOAT) for the treatment of acute and subacute complicated type B aortic dissection (TBAD). We retrospectively collected and analyzed the clinical data of patients with acute and subacute TBAD who were treated using the PETTICOAT technique at our center between March 2014 and March 2023. The primary endpoint was all-cause mortality; secondary endpoints were a composite of complications, such as entry flow, stent-graft-induced new entry (SINE), and re-intervention. The technical success was 92% (46/50). The perioperative mortality was 2% (1/50), and the procedure-related re-intervention was also 2% (1/50). The mean follow-up time was (74.9±33.9) months. The mortality was 4.1% (2/49). The incidence of aortic-related complications was 8.2% (4/49), including new entry flow, 2 retrograde type A aortic dissections, and 1 distal stent graft-induced new entry SINE. The procedure-related re-intervention rate was 4.1% (2/49). After 5 years of follow-up, the total aortic diameter at the renal artery level was reduced from that at the third year of follow-up but was still significantly larger than preoperatively (26.9±6.6 mm vs. 24.1±4.2 mm, p=0.013). While at the covered stent, bare stent, stentless, and celiac artery (CA) levels, the total aortic diameters did not change significantly compared with preoperative values, whereas true lumen (TL) diameters and TL ratios were maintained at obviously higher levels than preoperative. The rate of complete thrombosis of false lumen in the thoracic aortic segment was significantly higher than that in the abdominal aortic segment (79.6% vs 30.6%, p=0.0001). The results indicated that the PETTICOAT technique is safe and effective and could promote positive remodeling of the aorta from the level of the covered stent to the CA. Remodeling of the distal abdominal aorta may fluctuate and requires close follow-up review. The long-term results from our center suggest that the PETTICOAT technique promotes positive remodeling of the aorta from the level of the covered stent to the CA; whereas this advantage does not seem to be significant in the more distal segment of the abdominal aorta, mainly at the level of RA and distal. Therefore, further procedures may be required for aortic dissection of the abdominal segment. In addition, aortic remodeling may fluctuate to some extent during the follow-up period, especially in the abdominal visceral region, so close follow-up review is quite important, and prompt re-intervention is required if necessary.

Isosmotic Striction of Rat Aorta Smooth Muscle Cells During Activation of Purinergic Receptors: Role of Chlorine Transport

We studied the effect of the purinergic signaling system and Cl-transporters on vascular smooth muscle cells (SMC) isosmotic striction that occurs when osmotic pressure is normalized after prolonged incubation in a hypoosmotic medium. The study was performed with the method of myography on endothelium-denuded ring segments of the male Wistar rats aorta. Isosmotic striction was induced by placing the vascular segments in normosmotic Krebs solution containing 120 mM NaCl after a 40-minute incubation in a hyposmotic Krebs solution containing 40 mM NaCl. Purinergic receptors were activated by adenosine 5'-triphosphate (ATP, 500 μM) as nonselective P2X and P2Y receptor agonist, and uridine 5'-triphosphate (UTP, 500 μM) as selective P2Y receptor agonist. ATP and UTP eliminated the transient nature of the aorta SMC isosmotic striction without affecting its amplitude. Pretreatment of vascular segments with ATP and UTP during incubation in a hyposmotic solution completely suppressed the development of isosmotic striction in the presence of ATP or UTP, but did not affect isosmotic striction without activators of purinergic receptors. The inhibitor of Na+, K+, 2Cl--cotransport (NKCC) bumetanide (100 μM) abolished isosmotic striction in the presence of ATP, but not UTP, but restored its transient character. A non-selective blocker of Cl– channels and Cl–, HCO3– exchanger DIDS (100 μM) suppressed the development of isosmotic striction both in the presence of ATP and UTP. The potassium channel blocker tetraethylammonium (10 mM) potentiates the constrictor action of UTP on isosmotic striction. We suppose purinergic receptors eliminate the transient isosmotic striction by activating Cl– currents through activation of P2Y receptors. The mechanism of interaction between the purinergic signaling system and Cl– transport during changes in cell volume requires further study.

Red blood cells from patients with ST-elevation myocardial infarction and elevated C-reactive protein levels induce endothelial dysfunction.

Endothelial dysfunction is an early consequence of vascular inflammation and a driver of coronary atherosclerotic disease leading to myocardial infarction. The red blood cells (RBCs) mediate endothelial dysfunction in patients at cardiovascular risk, but their role in patients with acute myocardial infarction is unknown. This study aimed to investigate if RBCs from patients with ST-elevation myocardial infarction (STEMI) induced endothelial dysfunction and the role of systemic inflammation in this effect. RBCs from patients with STEMI and aged-matched healthy controls were co-incubated with rat aortic segments for 18h followed by evaluation of endothelium-dependent (EDR) and -independent relaxation (EIDR). RBCs and aortic segments were also analyzed for arginase and oxidative stress. The patients were divided into groups depending on C-reactive protein (CRP) levels at admission. RBCs from patients with STEMI and CRP levels >2 mg/L induced impairment of EDR, but not EIDR, compared to RBCs from STEMI and CRP <2 mg/L and healthy controls. Aortic expression of arginase 1 was increased following incubation with RBCs from patients with STEMI and CRP >2, and arginase inhibition prevented the RBC-induced endothelial dysfunction. RBCs from patients with STEMI and CRP >2 had increased reactive oxygen species compared to RBCs from patients with CRP <2 and healthy controls. Vascular inhibition of NADPH oxidases and increased dismutation of superoxide improved EDR. RBCs from patients with STEMI and low-grade inflammation induce endothelial dysfunction through a mechanism involving arginase 1 as well and increased RBC and vascular superoxide by NADPH oxidases.

Urgent hybrid repair of a symptomatic dissection-related type ii thoracoabdominal aortic aneurysms.

Emergency repair of type II thoraco-abdominal aortic aneurysms is burdened by high perioperative morbidity and mortality. We report the case of a symptomatic type II post-dissection thoraco-abdominal aortic aneurysm that was treated by mean of a hybrid technique. The repair was carried out through two stages. In the first stage, we deployed two imbricated stent grafts in the descending thoracic aorta. A left carotid to left subclavian artery by-pass was preemptively performed in order to obtain a proper proximal landing zone and as part of the spinal cord protective maneuvers. The endovascular first stage was effective in obtaining proximal sealing but, as expected, did not prevent distal reperfusion of the aneurysmatic false lumen. Few hours later, we moved on to the second stage in which we repaired the aneurysmal distal thoracic and abdominal aortic segment by mean of a multibranched synthetic graft. The repair was carried out through a left thoracophrenolaparotomy in the VII intercostal space. A left passive arterial by-pass and selective cold renal and warm visceral perfusion were adopted in order to provide organ protection. Technical success was achieved and radiologically confirmed. The patient experienced a mild postoperative paraplegia, which almost completely regressed after a neuro-motor rehabilitation program.

Impact of systemic lupus erythematosus on cardiovascular morphologic and functional phenotypes: a Mendelian randomization analysis.

Previous studies have established a correlation between systemic lupus erythematosus (SLE) and cardiovascular health, but the potential causal effects of SLE on heart function and structure remain poorly understood. Cardiovascular magnetic resonance imaging (CMR), a novel non-invasive technique, provides a unique assessment of cardiovascular structure and function, making it an essential tool for evaluating the risk of heart disease. In this study, we performed a Mendelian randomization analysis to determine the causal relationship between SLE and CMR traits. Genetic variants independently linked to SLE were selected from a genome-wide association study (GWAS) containing 5,201 cases and 9,066 controls as instrumental variables. A set of 82 CMR traits was obtained from a recent GWAS, serving as preclinical indicators and providing preliminary insights into the morphology and function of the four cardiac chambers and two aortic segments. Primary analysis employed a two-sample Mendelian randomization study using the inverse-variance weighted method. Heterogeneity testing, sensitivity analyses, and instrumental variable strength assessments confirmed the robustness of the findings. SLE exhibited a correlation with increased stroke volume (βLVSV = 0.007, P = 0.045), regional peak circumferential strain (βEcc_AHA_9 = 0.013, P = 0.002; βEcc_AHA_12 = 0.009, P = 0.043; βEcc_AHA_14 = 0.013, P = 0.006), and global peak circumferential strain of the LV (βEcc_global = 0.010, P = 0.022), as well as decreased regional radial strain (βErr_AHA_11 = -0.010, P = 0.017). This research presents evidence of a potential causal association between traits of SLE and alterations in cardiac function, guiding cardiac examinations and disease prevention in lupus patients.

Incidentally detected noninfectious thoracic aortitis: A clinical approach.

Noninfectious aortitis is occasionally detected incidentally, either on imaging or on histopathologic review after open thoracic aortic surgery. It can present as a clinically asymptomatic, seemingly focal lesion, as diffuse inflammation throughout several aortic segments but sparing the branch vessels, or as a manifestation of a widespread systemic condition. Treatment differs based on etiology, so once identified, all patients with aortitis need a thorough evaluation, laboratory tests, complete large-vessel imaging, and a referral to a vasculitis expert. All patients with aortitis are at high risk of future vascular complications and should be followed with serial clinical evaluations and imaging.

Successful Factors for Improving Aortic Remodeling with Thoracic Endovascular Repair and Bare Stent Extension

ObjectiveProximal ExTension to Induce COmplete ATtachment (PETTICOAT), which utilizes downstream bare metal stents for structural support, demonstrates potential, yet its adoption is limited by variable outcomes. This study elucidates the potential of PETTICOAT in aortic dissection, emphasizing the determinants that guide patient selection. MethodsA retrospective analysis of 60 patients who underwent full PETTICOAT for aortic dissections was conducted. A multivariate logistic regression model identified predictors of favorable aortic remodeling. Patients underwent standardized follow-up with CT scans to assess size, volumetric changes, and anatomical conditions. Selection criteria included full PETTICOAT application and a minimum three-month follow-up. Demographics, preoperative conditions, and procedural details were collected and analyzed. ResultsThe analysis identified predictors of favorable aortic remodeling, including age over 60, a larger downstream aorta stent graft, a smaller abdominal aorta (<450mm2), and oral angiotensin II receptor blocker (ARB) administration. Over a median 47.5-month follow-up, survival rates in the favorable remodeling (97.3%) and unfavorable groups (100%) were similar. Downstream aortic event-free survival rates did not significantly differ (89.2% vs. 73.9%), although the unfavorable group had a relatively higher incidence of distal stent-induced new entries (26.1% vs. 8.1%). ConclusionsThe PETTICOAT concept effectively enhances aortic remodeling in complex aortic dissections. Predictors for favorable remodeling, including age, stent graft sizing, aortic diameter, and ARB therapy, offer insights for optimizing patient selection. This approach improves survival outcomes, mitigates risks associated with untreated aortic segments, and provides a minimally invasive solution for aortic dissections. Despite some outcome variations, the technique holds promise for addressing the challenges of aortic dissections, with the potential for further refinement in patient selection and technique application.

Age-peculiarities of L-arginine, inosine and meldonium effects on the adult and old rat vascular wall reactivity

Abstract. Cardiovascular diseases are most common in older people. The functional state of the vascular endothelium is important in the pathogenesis of cardiovascular diseases. Numerous physiologically active substances with different mechanisms of action can affect endothelial function L-arginine, inosine and meldonium caught our attention. Combination therapy is a promising direction in treating circulatory system diseases. This work aimed to establish the age-related characteristics of L-arginine, inosine and meldonium and their combination (Melarginine) on the vascular wall reactivity in adult and old rats to substantiate the occurrence of these cases in cardiology and geriatrics. Experiments were carried out on isolated norepinephrine (10-7 mol/l) segments of the thoracic aorta of adult (8-10 months) and old (21-23 months) outbred male rats. It was shown that the vasodilatory effect of L-arginine, inosine and meldonium and their combination (Melarginine) was insignificant. At the same time, the isolated vascular segment relaxation of old rats under the studied substances was significantly greater compared to adult animals. It should be noted that the vasodilatory effect of acetylcholine in old rats was significantly less than in adults. This indicates the practical endothelium preservation in adult animals and its damage in old ones. The greater sensitivity of the vascular wall of old rats to the action of L-arginine, inosine and meldonium and their combination Melarginine indicates their action is directed at restoring endothelial function in old animals. This suggests the feasibility of using Melarginine in geriatric practice for cardiovascular disease treatment in the future. _________________________________________________________________________________________ Keywords: vessel reactivity; ageing; L-arginine; inosine; meldonium; Melarginine

Impaired Peripheral Vascular Function Following Ischemic Stroke in Mice: Potential Insights into Blood Pressure Variations in the Post-Stroke Patient.

High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine-induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham = -7.499, LogIC50 Stroke = -7.350, p = 0.0132, n = 19, 31 respectively). The vasodilatory responses to SNP were identical in the isolated aortas in the sham and stroke groups. Phenylephrine-induced vasoconstriction was impaired in the aortas isolated from the stroke animals in comparison to their sham treatment counterparts (Sham LogEC50= -6.652 vs. Stroke LogEC50 = -6.475, p < 0.001). Our study demonstrates that 24 h post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. The aortas from the stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while the endothelium-independent vasodilatory responses were preserved. Since both the vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke.

Antihypertensive Effects of Lindera erythrocarpa Makino via NO/cGMP Pathway and Ca2+ and K+ Channels.

Studies have demonstrated the therapeutic effects of Lindera plants. This study was undertaken to reveal the antihypertensive properties of Lindera erythrocarpa leaf ethanolic extract (LEL). Aorta segments of Sprague-Dawley rats were used to study the vasodilatory effect of LEL, and the mechanisms involved were evaluated by treating specific inhibitors or activators that affect the contractility of blood vessels. Our results revealed that LEL promotes a vasorelaxant effect through the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway, blocking the Ca2+ channels, opening the K+ channels, and inhibiting the vasoconstrictive action of angiotensin II. In addition, the effects of LEL on blood pressure were investigated in spontaneously hypertensive rats by the tail-cuff method. LEL (300 or 1000 mg/kg) was orally administered to the rats, and 1000 mg/kg of LEL significantly lowered the blood pressure. Systolic blood pressure decreased by -20.06 ± 4.87%, and diastolic blood pressure also lowered by -30.58 ± 5.92% at 4 h in the 1000 mg/kg LEL group. Overall, our results suggest that LEL may be useful to treat hypertensive diseases, considering its vasorelaxing and hypotensive effects.

LCZ696, an Angiotensin Receptor-Neprilysin Inhibitor, Ameliorates Endothelial Dysfunction in Diabetic C57BL/6 Mice.

LCZ696 (sacubitril/valsartan) exerts cardioprotective effects. Recent studies have suggested that it improves the endothelial function; however, the underlying mechanisms have not been thoroughly investigated. We investigated whether LCZ696 ameliorates diabetes-induced endothelial dysfunction. Diabetes was induced using streptozotocin in 8-week-old male C57BL/6 mice. Diabetic mice were randomly assigned to receive LCZ696 (100 mg/kg/day), valsartan (50 mg/kg/day), or a vehicle for three weeks. The endothelium-dependent and endothelium-independent vascular responses of the aortic segments were determined based on the response to acetylcholine and sodium nitroprusside, respectively. Human umbilical vein endothelial cells (HUVEC) and aortic segments obtained from C57BL/6 mice were used to perform in vitro and ex vivo experiments, respectively. LCZ696 and valsartan reduced the blood pressure in diabetic mice (P＜0.05). The administration of LCZ696 (P＜0.001) and valsartan (P＜0.01) ameliorated endothelium-dependent vascular relaxation, but not endothelium-independent vascular relaxation, under diabetic conditions. LCZ696, but not valsartan, increased eNOSSer1177 (P=0.06) and Akt (P＜0.05) phosphorylation in the aorta. In HUVEC, methylglyoxal (MGO), a major precursor of advanced glycation end products, decreased eNOSSer1177 phosphorylation (P＜0.05) and increased eNOSThr495 phosphorylation (P＜0.001). However, atrial natriuretic peptide (ANP) reversed these effects. ANP also ameliorated the MGO-induced impairment of endothelium-dependent vascular relaxation in the aortic segments (P＜0.05), although L-NAME completely blocked this effect (P＜0.001). LCZ696 ameliorated diabetes-induced endothelial dysfunction by increasing the bioavailability of ANP. Our findings suggest that LCZ696 has a vascular protective effect in a diabetic model and highlight that it may be more effective than valsartan.

Abstract P309: Vasodilating Effects of Macrolides: ex vivo and in vivo study

Background: Anecdotal reports showed a decrease in blood pressure (BP) values in subjects assuming macrolide antibiotics when co-administered with calcium channel blockers. Recently, in the MAPA study, in patients with primary hypertension given a single dose of macrolide a decrease in BP was observed. However, whether macrolides induce per se vasorelaxation remains unknown. Aim: To investigate if macrolides induce vasorelaxation and to identify the underlying mechanisms. Methods: The effects of 3 macrolides (roxithromycin, azithromycin, clarithromycin) were investigated in a wire myograph in aortas isolated from C57BL/6J mice, following standard protocols. Relaxation/contraction was evaluated in phenylephrine pre-contracted aorta segments exposed to different macrolide concentrations [10 -10 M to 10 -5 M]. Longer-term effects of azithromycin (50 mg/Kg/d intraperitoneally for 14 days) were investigated in vivo in a mouse model of Ang II-induced hypertension. BP was measured with the tail-cuff method; functional and structural/mechanical properties of the aorta and mesenteric arteries were evaluated with wire or pressure myograph, as appropriate. Results: After exposure to macrolides, phenylephrine pre-contracted mice aorta segments showed relaxation (maximum effect: -15-20% vs DMSO). The vasodilating effect was abolished by the removal of the endothelium, and was blunted by L-NAME. In the vivo studies treatment with azithromycin lowered BP values and prevented Ang II-induced endothelial dysfunction. Conclusions: Macrolides exert a vasodilatory action that involves endothelium-dependent NO release. In a model of Ang II-mediated hypertension, azithromycin exerted a BP-lowering effect.

МОРФОЛОГИЧЕСКАЯ ОЦЕНКА ПРОЦЕССА ФОРМИРОВАНИЯ НЕОИНТИМЫ И VASA VASORUM ПОСЛЕ ПРОТЕЗИРОВАНИЯ БРЮШНОЙ АОРТЫ В ЭКСПЕРИМЕНТЕ

Background. The article considers one of the most important problems in modern vascular surgery – the choice of a vascular graft for performing reconstructive surgical operations on the great vessels. The aim of this study is to perform a morphological comparison of the neointima and vasa vasorum formation in an experiment using various types of vascular grafts. Material and methods. The study was performed on female white pigs (n=12). The animals were divided into 2 groups: group 1 – those with implantation of a synthetic vascular graft made of Dacron coated with modified gelatin, group 2 – those with implantation of a biological vascular graft made of bovine xenopericardium. The material for histological examination was explanted vascular grafts with segments of the abdominal aorta. The sections were stained with hematoxylin and eosin, and Masson trichrome. For the morphometric study we used digital images of histological preparations obtained from a Leica DFC425 digital camera as well as scanned digital images of histological preparations obtained from a Leica Aperio AT2 scanner. Results. Morphometric examination of the neointima revealed that 3 and 6 months after surgery, the thickness of the neointima when using a synthetic vascular graft was significantly greater than when using a biological vascular graft from bovine xenopericardium (p&lt;0.001). Endothelization of the neointima was noted only in the group of animals with a bioprosthesis. At the same time, an earlier and more pronounced formation of vasa vasorum was noted in animals with an implanted biological vascular graft. Conclusion. The formation of neointima was noted when using both biological and synthetic vascular grafts. In the group of animals with an implanted biological vascular graft from bovine xenopericardium, neointima endothelization and pronounced vascularization were noted, which indicates a greater physiological potential of this graft and is a factor reducing the risk of thrombosis.