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International Journal of Hypertension 2024Ouabain, a Na, K-ATPase inhibitor, is elevated in hypertensive patients. Evidence suggests ouabain contributes to hypertension mainly through activation of the...
BACKGROUND
Ouabain, a Na, K-ATPase inhibitor, is elevated in hypertensive patients. Evidence suggests ouabain contributes to hypertension mainly through activation of the sympathetic nervous system (SNS). Renal nerves play a vital role in the regulation of SNS activity, so we hypothesize that renal denervation may attenuate the development of ouabain-induced hypertension.
METHODS AND RESULTS
Forty Sprague-Dawley rats were divided into following groups ( = 10 each): control group (sham surgery plus intraperitoneal saline injection), RDN group (renal denervation (RDN) plus intraperitoneal saline injection), ouabain group (sham surgery plus intraperitoneal ouabain injection), and ouabain + RDN group (RDN plus intraperitoneal ouabain injection). After eight weeks, compared with the control group, rats in the ouabain group exhibited elevated blood pressure ( < 0.05), increased plasma epinephrine, norepinephrine, angiotensin II, and aldosterone levels ( < 0.05). These indexes could be significantly ameliorated by RDN. RDN also reduced the thickening of aortic tunica media and downregulated the expression of proliferating cell nuclear antigen (PCNA) in the thoracic aorta induced by ouabain. Masson staining and echocardiography showed that myocardial fibrosis and increased left ventricular mass in the ouabain group could be attenuated by RDN.
CONCLUSIONS
The present study reveals that renal nerves play an important role in the development of ouabain-induced hypertension. RDN could inhibit the pressor effect and the myocardial remodeling induced by ouabain potentially via inhibiting catecholamine release and vascular smooth muscle cell proliferation. Clinical studies are needed to explore whether RDN may exhibit better antihypertensive effects on hypertensive patients with high plasma ouabain levels as compared to those with normal plasma ouabain levels.
PubMed: 38957519
DOI: 10.1155/2024/4763189 -
International Journal of Emergency... Jul 2024The presentation of acute aortic dissection can pose a challenge for emergency physicians, as it may occur without pain. Atypical presentations can lead to significant...
BACKGROUND
The presentation of acute aortic dissection can pose a challenge for emergency physicians, as it may occur without pain. Atypical presentations can lead to significant delays in diagnosis and increased mortality rates.
CASE DESCRIPTION
Our case illustrates that isolated painless syncope can be a rare presenting symptom of acute aortic dissection type A. What is unique about our case is the limited extension of the dissection tear and the availability of Holter monitoring during the syncopal episode.
CONCLUSION
This constellation provides insight into the pathophysiological mechanism of the syncope in this patient. Mechanisms of syncope related to acute aortic dissection are diverse. We show that vasovagal activation not related to pain can be the underlying mechanism of syncope in acute aortic dissection type A. Although excessive vasovagal tone in the setting of aortic dissection has been hypothesized in the past, it has never been as clearly illustrated as in the present case. This also highlights the challenge in risk stratification of syncope in the emergency department.
PubMed: 38956477
DOI: 10.1186/s12245-024-00664-8 -
PloS One 2024Bicuspid aortic valves (BAV) are frequently associated with ascending aortic aneurysms. The etiology is incompletely understood, but genetic factors, in addition to flow...
BACKGROUND
Bicuspid aortic valves (BAV) are frequently associated with ascending aortic aneurysms. The etiology is incompletely understood, but genetic factors, in addition to flow perturbations, are likely involved. Since loss of contractility and elaboration of extracellular matrix in the vessel wall are features of BAV-associated aortopathy, phenotypic modulation of smooth muscle cells (SMCs) may play a role.
METHODS
Ascending aortic tissue was collected intra-operatively from 25 individuals with normal (i.e., tricuspid) aortic valves (TAV) and from 25 individuals with BAVs. For both TAV and BAV, 10 patients had non-dilated (ND) and 15 patients had dilated (D) aortas. SMCs were isolated and cultured from a subset of patients from each group. Aortic tissue and SMCs were fluorescently immunolabeled for SMC phenotypic markers (i.e., alpha-smooth muscle actin (ASMA, contractile), vimentin (synthetic) and p16INK4a and p21Cip1 (senescence). SMCs were also analyzed for replicative senescence in culture.
RESULTS
In normal-sized and dilated BAV aortas, SMCs switched from the contractile state to either synthetic or senescent phenotypes, as observed by loss of ASMA (ND: P = 0.001, D: P = 0.002) and associated increases in vimentin (ND: P = 0.03, D: P = 0.004) or p16/p21 (ND: P = 0.03, D: P<0.0001) compared to TAV. Dilatation of the aorta exacerbated SMC phenotypic switching in both BAV and TAV aortas (all P<0.05). In SMCs cultured from normal and dilated aortas, those isolated from BAV reached replicative senescence faster than those from TAV aortas (all P = 0.02). Furthermore, there was a stark inverse correlation between ASMA and cell passage number in BAV SMCs (ND: P = 0.0006, D: P = 0.01), but not in TAV SMCs (ND: P = 0.93, D: P = 0.20).
CONCLUSIONS
The findings of this study provide direct evidence from cell culture studies implying that SMCs switch from the contractile state to either synthetic or senescent phenotypes in the non-dilated BAV aorta. In cultured SMCs from both non-dilated and dilated aortas, we found that this process may precede dilatation and accompany aneurysm development in BAV. Our findings suggest that therapeutically targeting SMC phenotypic modulation in BAV patients may be a viable option to prevent or delay ascending aortic aneurysm formation.
Topics: Humans; Aortic Valve; Bicuspid Aortic Valve Disease; Myocytes, Smooth Muscle; Heart Valve Diseases; Aorta; Male; Middle Aged; Phenotype; Female; Dilatation, Pathologic; Adult; Cellular Senescence; Cells, Cultured; Aged; Actins; Aortic Aneurysm; Vimentin
PubMed: 38954721
DOI: 10.1371/journal.pone.0306515 -
Journal of Cardiothoracic Surgery Jun 2024The outcomes of Thoracic Endovascular Aortic Repair (TEVAR) vary depending on thoracic aortic pathologies, comorbidities. This study presents our comprehensive...
BACKGROUND
The outcomes of Thoracic Endovascular Aortic Repair (TEVAR) vary depending on thoracic aortic pathologies, comorbidities. This study presents our comprehensive endovascular experience, focusing on exploring the outcome in long term follow-up.
METHODS
From 2006 to 2018, we conducted TEVAR on 97 patients presenting with various aortic pathologies. This retrospective cohort study was designed primarily to assess graft durability and secondarily to evaluate mortality causes, complications, reinterventions, and the impact of comorbidities on survival using Kaplan-Meier and Cox regression analyses.
RESULTS
The most common indication was thoracic aortic aneurysm (n = 52). Ten patients had aortic arch variations and anomalies, and the bovine arch was observed in eight patients. Endoleaks were the main complications encountered, and 10 of 15 endoleaks were type I endoleaks. There were 18 reinterventions; the most of which was TEVAR (n = 5). The overall mortality was 20 patients, with TEVAR-related causes accounting for 12 of these deaths, including intracranial bleeding in three patients. Multivariant Cox regression revealed chronic renal diseases (OR = 11.73; 95% CI: 2.04-67.2; p = 0.006), previous cardiac operation (OR = 14.26; 95% CI: 1.59-127.36; p = 0.01), and chronic obstructive pulmonary diseases (OR = 7.82; 95% CI: 1.43-42.78; p = 0.001) to be independent risk factors for 10-year survival. There was no significant difference in the survival curves of the various aortic pathologies. In the follow-up period, two non-symptomatic intragraft thromboses and one graft infection were found.
CONCLUSION
Comorbidities can increase the risk of TEVAR-related mortality without significantly impacting endoleak rates. TEVAR is effective for severe aortic pathologies, though long-term graft durability may be compromised by its thrombosis and infection.
Topics: Humans; Retrospective Studies; Male; Female; Middle Aged; Endovascular Procedures; Aorta, Thoracic; Aged; Blood Vessel Prosthesis Implantation; Treatment Outcome; Aortic Diseases; Postoperative Complications; Adult; Aortic Aneurysm, Thoracic; Follow-Up Studies; Time Factors; Endovascular Aneurysm Repair
PubMed: 38951901
DOI: 10.1186/s13019-024-02886-6 -
Thrombosis and Haemostasis Jul 2024Hereditary aortic diseases (hADs) increase the risk of aortic dissections and ruptures. Recently, we have established an objective approach to measure the rupture...
OBJECTIVE
Hereditary aortic diseases (hADs) increase the risk of aortic dissections and ruptures. Recently, we have established an objective approach to measure the rupture force of the murine aorta, thereby explaining the outcomes of clinical studies and assessing the added value of approved drugs in vascular Ehlers-Danlos syndrome (vEDS). Here, we applied our approach to six additional mouse hAD models.
MATERIAL AND METHODS
We used two mouse models ( and ) of Marfan syndrome (MFS) as well as one smooth-muscle-cell-specific knockout (SMKO) of and three CRISPR/Cas9-engineered knock-in models (, , and ). One of the two MFS models was subjected to 4-week-long losartan treatment. Per mouse, three rings of the thoracic aorta were prepared, mounted on a tissue puller, and uniaxially stretched until rupture.
RESULTS
The aortic rupture force of the SMKO and both MFS models was significantly lower compared with wild-type mice but in both MFS models higher than in mice modeling vEDS. In contrast, the , , and knock-in models presented no impaired aortic integrity. As expected, losartan treatment reduced aneurysm formation but surprisingly had no impact on the aortic rupture force of our MFS mice.
CONCLUSION
Our read-out system can characterize the aortic biomechanical integrity of mice modeling not only vEDS but also related hADs, allowing the aortic-rupture-force-focused comparison of mouse models. Furthermore, aneurysm progression alone may not be a sufficient read-out for aortic rupture, as antihypertensive drugs reducing aortic dilatation might not strengthen the weakened aortic wall. Our results may enable identification of improved medical therapies of hADs.
PubMed: 38950604
DOI: 10.1055/s-0044-1787957 -
Increasing the Maximum Detectable Flow Velocity in High-Frequency Ultrasound Vector Doppler Imaging.IEEE Transactions on Bio-medical... Jul 2024High-frequency ultrasound (HFUS; >30 MHz) Doppler imaging has been widely used in the imaging of small animals and humans because of its high resolution. Vector Doppler...
High-frequency ultrasound (HFUS; >30 MHz) Doppler imaging has been widely used in the imaging of small animals and humans because of its high resolution. Vector Doppler imaging (VDI) has certain advantages for visualizing complex flow patterns independent of the Doppler angle. However, no commercial HFUS VDI system is currently available; therefore, several studies have connected an ultrasound research platform (Verasonics Vantage 256) with an HFUS array transducer for HFUS VDI. Unfortunately, the maximum frame rate of this system is only 10 kHz at an operational frequency of 40 MHz because of limitations related to data transmission hardware, thereby restricting the maximum detectable velocity of Doppler measurements. To address this drawback, in the present study, an electrocardiography (ECG)-gating-based HFUS VDI system was developed to avoid Doppler flow aliasing in data acquisition by ultrasound research platform at its maximum frame rate of 10 kHz. The developed method aligns all tilted plane waves with the ECG R-wave, which avoids the trade-off between frame rate and tilted angles number in conventional VDI. The performance of the proposed data acquisition method in HFUS VDI was verified using a steady-flow phantom, for which estimation errors were less than 10% under different flow settings. In animal studies, peak flow velocities in the carotid artery, left ventricle, and aortic arch of wild-type mice were measured (approximately 55, 655, and 765 mm/s, respectively). Also, the HFUS VDI from the mitral regurgitation mice model was obtained to present the complex flow patterns through the proposed method. In contrast to the conventional method, no Doppler aliasing occurs in the proposed method because the frame rate is sufficient. The experimental results indicate the developed HFUS VDI has the potential to become a useful tool for vector flow visualization in small animals, even under a high flow velocity.
PubMed: 38949935
DOI: 10.1109/TBME.2024.3410244 -
World Journal of Experimental Medicine Jun 2024Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for... (Review)
Review
Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for its prevention and management, given its responsibility for more than 25000 deaths in the United States. AAs are classified based on their location or morphology. various pathophysiologic pathways including inflammation, the immune system and atherosclerosis have been implicated in its development. Inflammatory markers such as transforming growth factor β, interleukin-1β, tumor necrosis factor-α, matrix metalloproteinase-2 and many more may contribute to this phenomenon. Several genetic disorders such as Marfan syndrome, Ehler-Danlos syndrome and Loeys-Dietz syndrome have also been associated with this disease. Recent years has seen the investigation of novel management of AA, exploring the implication of different immune suppressors, the role of radiation in shrinkage and prevention, as well as minimally invasive and newly hypothesized surgical methods. In this narrative review, we aim to present the new contributing factors involved in pathophysiology of AA. We also highlighted the novel management methods that have demonstrated promising benefits in clinical outcomes of the AA.
PubMed: 38948412
DOI: 10.5493/wjem.v14.i2.91408 -
IDCases 2024Infections associated with healthcare manipulations, particularly bloodstream infections stemming from catheters and medical devices, significantly heighten the...
Infections associated with healthcare manipulations, particularly bloodstream infections stemming from catheters and medical devices, significantly heighten the probability of vertebral osteomyelitis. The diagnosis of infective endocarditis (IE) frequently overlaps with vertebral osteomyelitis (VO). In cases where individuals are suspected of having hematogenous vertebral osteomyelitis and have an intravascular catheter or device, it is recommended to undertake blood culture collection. We present a case of a 39-year-old male with a history of interventional AVM embolization and cerebral angiography, experiencing recurrent vertebral osteomyelitis. No definitive source of infection had been found, and transthoracic echocardiography (TTE) yielded negative results for IE. In Trans Esophageal Echocardiography (TEE), a retained micro-catheter extending from the aortic arch to the inguinal artery was discovered. Although we cannot definitively attribute the source of the osteomyelitis to the retained micro-catheter, no episodes of infection have been reported ever since. This case underscores the need to enhance our approaches and guidelines related to operating protocols in the surgical setting. Improving these guidelines can prevent similar occurrences in the future, emphasizing the importance of continuous improvement in healthcare practices.
PubMed: 38947558
DOI: 10.1016/j.idcr.2024.e02005 -
Atherosclerosis Jun 2024The role of aortic mineralization in the pathogenesis of acute type B aortic dissection (TBAD) is unclear. Whether thoracic aortic calcification (TAC) and circulating...
BACKGROUND AND AIMS
The role of aortic mineralization in the pathogenesis of acute type B aortic dissection (TBAD) is unclear. Whether thoracic aortic calcification (TAC) and circulating alkaline phosphatase (ALP) activity are associated with acute TBAD risk remains elusive.
METHODS
Observational and Mendelian randomization (MR) studies were conducted sequentially. Using propensity score matching (1:1) by age and sex, patients with acute TBAD (n = 125) were compared with control patients (n = 125). Qualitative (score) and quantitative (volume) analyses of the TAC burden on different thoracic aortic segments were conducted using non-enhanced computed tomography. Univariate and multivariate analyses were used to identify significant independent risk factors for TBAD and TAC burden, respectively. MR was finally used to determine the causal relationship between elevated ALP activity and TBAD risk.
RESULTS
The qualitative and quantitative analyses revealed that TAC burden was significantly higher in the TBAD group, except for in the ascending aortic segment (both p < 0.05). Preoperative circulating ALP was significantly elevated in the TBAD group (p < 0.001). The elevated TAC burden score on the descending thoracic aortic segment (odds ratio [OR] 3.31, 95% confidence interval [CI] 1.31-8.37) and increased ALP activity (OR 1.03, 95% CI 1.01-1.06) was independently associated with TBAD risk. Interestingly, ALP was significantly positively associated with TAC burden, and MR analyses confirmed that ALP genetically predicted TBAD risk.
CONCLUSIONS
Elevated ALP may trigger TBAD risk via the increased volume of TAC. Aortic mineralization may not protect the aorta itself.
PubMed: 38944894
DOI: 10.1016/j.atherosclerosis.2024.118519 -
Annals of Vascular Surgery Jun 2024Thoracic aortic aneurysms evolving within a type IIIb chronic aortic dissection are mostly treated with the deployment of an endograft. However, several cases of...
Thoracic aortic aneurysms evolving within a type IIIb chronic aortic dissection are mostly treated with the deployment of an endograft. However, several cases of dissecting aneurysms are associated with a significant dilatation of the aortic arch. These cases are usually managed in two steps : arch reconstruction or supra-aortic trunk debranching at first and a secondary graft deployment for the descending thoracic aorta. We present through this case series an alternative approach for this severe condition which consists in the replacement of the thoracic aorta from its hemi-arch to the distal thoracic or visceral aorta using a left thoracotomy. We deliberately neglected the remaining dissecting aorta if its diameter was below 45 mm, hypothesizing its non evolution after repair. From 2012 to 2021, 9 patients have been treated for a thoracic aneurysm evolving after a IIIb chronic aortic dissection using a left thoracotomy and a 19°C circulatory arrest. Immediate postoperative results show no mortality nor neurological disorders and the 7 years follow up for all of these 9 cases enlightened the absence of aneurysmal evolution especially for the distal anastomosis and the remaining dissected aorta. This work suggests that this direct approach strategy can definitively treat a thoracic dissecting aneurysm unsuitable for a simple endovascular treatment.
PubMed: 38944192
DOI: 10.1016/j.avsg.2024.04.012