ResearchPad - aorta https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Pulmonary ductal coarctation and left pulmonary artery interruption; pathology and role of neural crest and second heart field during development]]> https://www.researchpad.co/article/elastic_article_14709 In congenital heart malformations with pulmonary stenosis to atresia an abnormal lateral ductus arteriosus to left pulmonary artery connection can lead to a localised narrowing (pulmonary ductal coarctation) or even interruption We investigated embryonic remodelling and pathogenesis of this area.Material and methodsNormal development was studied in WntCre reporter mice (E10.0–12.5) for neural crest cells and Nkx2.5 immunostaining for second heart field cells. Data were compared to stage matched human embryos and a VEGF120/120 mutant mouse strain developing pulmonary atresia.ResultsNormal mouse and human embryos showed that the mid-pharyngeal endothelial plexus, connected side-ways to the 6th pharyngeal arch artery. The ventral segment formed the proximal pulmonary artery. The dorsal segment (future DA) was solely surrounded by neural crest cells. The ventral segment had a dual outer lining with neural crest and second heart field cells, while the distal pulmonary artery was covered by none of these cells. The asymmetric contribution of second heart field to the future pulmonary trunk on the left side of the aortic sac (so-called pulmonary push) was evident. The ventral segment became incorporated into the pulmonary trunk leading to a separate connection of the left and right pulmonary arteries. The VEGF120/120 embryos showed a stunted pulmonary push and a variety of vascular anomalies.SummarySide-way connection of the DA to the left pulmonary artery is a congenital anomaly. The primary problem is a stunted development of the pulmonary push leading to pulmonary stenosis/atresia and a subsequent lack of proper incorporation of the ventral segment into the aortic sac. Clinically, the aberrant smooth muscle tissue of the ductus arteriosus should be addressed to prohibit development of severe pulmonary ductal coarctation or even interruption of the left pulmonary artery. ]]> <![CDATA[Monitoring of cardiovascular physiology augmented by a patient-specific biomechanical model during general anesthesia. A proof of concept study]]> https://www.researchpad.co/article/elastic_article_14629 During general anesthesia (GA), direct analysis of arterial pressure or aortic flow waveforms may be inconclusive in complex situations. Patient-specific biomechanical models, based on data obtained during GA and capable to perform fast simulations of cardiac cycles, have the potential to augment hemodynamic monitoring. Such models allow to simulate Pressure-Volume (PV) loops and estimate functional indicators of cardiovascular (CV) system, e.g. ventricular-arterial coupling (Vva), cardiac efficiency (CE) or myocardial contractility, evolving throughout GA. In this prospective observational study, we created patient-specific biomechanical models of heart and vasculature of a reduced geometric complexity for n = 45 patients undergoing GA, while using transthoracic echocardiography and aortic pressure and flow signals acquired in the beginning of GA (baseline condition). If intraoperative hypotension (IOH) appeared, diluted norepinephrine (NOR) was administered and the model readjusted according to the measured aortic pressure and flow signals. Such patients were a posteriori assigned into a so-called hypotensive group. The accuracy of simulated mean aortic pressure (MAP) and stroke volume (SV) at baseline were in accordance with the guidelines for the validation of new devices or reference measurement methods in all patients. After NOR administration in the hypotensive group, the percentage of concordance with 10% exclusion zone between measurement and simulation was >95% for both MAP and SV. The modeling results showed a decreased Vva (0.64±0.37 vs 0.88±0.43; p = 0.039) and an increased CE (0.8±0.1 vs 0.73±0.11; p = 0.042) in hypotensive vs normotensive patients. Furthermore, Vva increased by 92±101%, CE decreased by 13±11% (p < 0.001 for both) and contractility increased by 14±11% (p = 0.002) in the hypotensive group post-NOR administration. In this work we demonstrated the application of fast-running patient-specific biophysical models to estimate PV loops and functional indicators of CV system using clinical data available during GA. The work paves the way for model-augmented hemodynamic monitoring at operating theatres or intensive care units to enhance the information on patient-specific physiology.

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<![CDATA[Retrospectively ECG-gated helical vs. non-ECG-synchronized high-pitch CTA of the aortic root for TAVI planning]]> https://www.researchpad.co/article/elastic_article_13825 Multidetector computed tomography (MDCT) plays a key role in patient assessment prior to transcatheter aortic valve implantation (TAVI). However, to date no consensus has been established on what is the optimal pre-procedural imaging protocol. Variability in pre-TAVI acquisition protocols may lead to discrepancies in aortic annulus measurements and may potentially influence prosthesis size selection.PurposeThe current study evaluates the magnitude of differences in aortic annulus measurements using max-systolic, end-diastolic, and non-ECG-synchronized imaging, as well as the impact of method on prosthesis size selection.Material and methodsFifty consecutive TAVI-candidates, who underwent retrospectively-ECG-gated CT angiography (CTA) of the aortic root, directly followed by non-ECG-synchronized high-pitch CT of the entire aorta, were retrospectively included. Aortic root dimensions were assessed at each 10% increment of the R-R interval (0–100%) and on the non-ECG-synchronized scan. Dimensional changes within the cardiac cycle were evaluated using a 1-way repeated ANOVA. Agreement in measurements between max-systole, end-diastole and non-ECG-synchronized scans was assessed with Bland-Altman analysis.ResultsMaximal dimensions of the aortic root structures and minimum annulus-coronary ostia distances were measured during systole. Max-systolic measurements were significantly and substantially larger than end-diastolic (p<0.001) and non-ECG-synchronized measurements (p<0.001). Due to these discrepancies, the three methods resulted in the same prosthesis size selection in only 48–62% of patients.ConclusionsThe systematic differences between max-systolic, end-diastolic and non-ECG-synchronized measurements for relevant aortic annular dimensions are both statistically significant and clinically relevant. Imaging strategy impacts prosthesis size selection in nearly half the TAVI-candidates. End-diastolic and non-ECG-synchronized imaging does not provide optimal information for prosthesis size selection. Systolic image acquisition is necessary for assessment of maximal annular dimensions and minimum annulus-coronary ostia distances. ]]> <![CDATA[Exploring magnetohydrodynamic voltage distributions in the human body: Preliminary results]]> https://www.researchpad.co/article/5c89777ed5eed0c4847d2e42

Background

The aim of this study was to noninvasively measure regional contributions of vasculature in the human body using magnetohydrodynamic voltages (VMHD) obtained from electrocardiogram (ECG) recordings performed inside MRI’s static magnetic field (B0). Integrating the regional VMHD over the Swave-Twave segment of the cardiac cycle (Vsegment) provides a non-invasive method for measuring regional blood volumes, which can be rapidly obtained during MRI without incurring additional cost.

Methods

VMHD was extracted from 12-lead ECG traces acquired during gradual introduction into a 3T MRI. Regional contributions were computed utilizing weights based on B0’s strength at specified distances from isocenter. Vsegment mapping was performed in six subjects and validated against MR angiograms (MRA).

Results

Fluctuations in Vsegment, which presented as positive trace deflections, were found to be associated with aortic-arch flow in the thoracic cavity, the main branches of the abdominal aorta, and the bifurcation of the common iliac artery. The largest fluctuation corresponded to the location where the aortic arch was approximately orthogonal to B0. The smallest fluctuations corresponded to areas of vasculature that were parallel to B0. Significant correlations (specifically, Spearman’s ranked correlation coefficients of 0.96 and 0.97 for abdominal and thoracic cavities, respectively) were found between the MRA and Vsegment maps (p < 0.001).

Conclusions

A novel non-invasive method to extract regional blood volumes from ECGs was developed and shown to be a rapid means to quantify peripheral and abdominal blood volumes.

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<![CDATA[Automated localization and quality control of the aorta in cine CMR can significantly accelerate processing of the UK Biobank population data]]> https://www.researchpad.co/article/5c6f151bd5eed0c48467adda

Introduction

Aortic distensibility can be calculated using semi-automated methods to segment the aortic lumen on cine CMR (Cardiovascular Magnetic Resonance) images. However, these methods require visual quality control and manual localization of the region of interest (ROI) of ascending (AA) and proximal descending (PDA) aorta, which limit the analysis in large-scale population-based studies. Using 5100 scans from UK Biobank, this study sought to develop and validate a fully automated method to 1) detect and locate the ROIs of AA and PDA, and 2) provide a quality control mechanism.

Methods

The automated AA and PDA detection-localization algorithm followed these steps: 1) foreground segmentation; 2) detection of candidate ROIs by Circular Hough Transform (CHT); 3) spatial, histogram and shape feature extraction for candidate ROIs; 4) AA and PDA detection using Random Forest (RF); 5) quality control based on RF detection probability. To provide the ground truth, overall image quality (IQ = 0–3 from poor to good) and aortic locations were visually assessed by 13 observers. The automated algorithm was trained on 1200 scans and Dice Similarity Coefficient (DSC) was used to calculate the agreement between ground truth and automatically detected ROIs.

Results

The automated algorithm was tested on 3900 scans. Detection accuracy was 99.4% for AA and 99.8% for PDA. Aorta localization showed excellent agreement with the ground truth, with DSC ≥ 0.9 in 94.8% of AA (DSC = 0.97 ± 0.04) and 99.5% of PDA cases (DSC = 0.98 ± 0.03). AA×PDA detection probabilities could discriminate scans with IQ ≥ 1 from those severely corrupted by artefacts (AUC = 90.6%). If scans with detection probability < 0.75 were excluded (350 scans), the algorithm was able to correctly detect and localize AA and PDA in all the remaining 3550 scans (100% accuracy).

Conclusion

The proposed method for automated AA and PDA localization was extremely accurate and the automatically derived detection probabilities provided a robust mechanism to detect low quality scans for further human review. Applying the proposed localization and quality control techniques promises at least a ten-fold reduction in human involvement without sacrificing any accuracy.

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<![CDATA[Numerical and in-vitro experimental assessment of the performance of a novel designed expanded-polytetrafluoroethylene stentless bi-leaflet valve for aortic valve replacement]]> https://www.researchpad.co/article/5c5b528cd5eed0c4842bcb44

The expanded polytetrafluoroethylene (ePTFE) heart valve can serve as a viable option for prosthetic aortic valve. In this study, an ePTFE bi-leaflet valve design for aortic valve replacement (AVR) is presented, and the performance of the proposed valve was assessed numerically and experimentally. The valve was designed using CAE software. The dynamic behavior of the newly designed bi-leaflet valve under time-varying physiological pressure loading was first investigated by using commercial finite element code. Then, in-vitro tests were performed to validate the simulation and to assess the hemodynamic performance of the proposed design. A tri-leaflet ePTFE valve was tested in-vitro under the same conditions as a reference. The maximum leaflet coaptation area of the bi-leaflet valve during diastole was 216.3 mm2. When fully closed, no leakage gap was observed and the free edges of the molded valve formed S-shaped lines. The maximum Von Mises stress during a full cardiac cycle was 4.20 MPa. The dynamic performance of the bi-leaflet valve was validated by the in-vitro test under physiological aortic pressure pulse. The effective orifice area (EOA), mean pressure gradient, regurgitant volume, leakage volume and energy loss of the proposed valve were 3.14 cm2, 8.74 mmHg, 5.93 ml/beat, 1.55 ml/beat and 98.99 mJ, respectively. This study reports a novel bi-leaflet valve design for AVR. The performance of the proposed valve was numerically and experimentally assessed. Compared with the reference valve, the proposed design exhibited better structural and hemodynamic performances, which improved valve competency. Moreover, the performance of the bi-leaflet design is comparable to commercialized valves available on the market. The results of the present study provide a viable option for the future clinical applications.

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<![CDATA[Relationship between the extent of aortic replacement and stent graft for acute DeBakey type I aortic dissection and outcomes: Results from a medical center in Taiwan]]> https://www.researchpad.co/article/5c390bbcd5eed0c48491e113

Background

Total arch replacement (TAR) and/or stent graft implantation has been proposed as the primary surgical treatment for acute DeBakey type I aortic dissection. However, the suggestion was based on excellent outcomes of high-volume or aortic centers. How about the real results in most places around the world? The purpose of this study was intended to compared in-hospital mortality, major complications, and aortic remodeling between TAR and/or stent graft implantation in a medical center of northern Taiwan.

Methods

Between January 2008 and August 2017, 156 patients with acute type I aortic dissection underwent surgery at our institution, including proximal aortic replacement only (Group I, n = 72), concomitant TAR (Group II, n = 23), concomitant TAR extended with stent grafting (Group III, n = 45), and proximal aortic replacement with descending aortic stent grafting (Group IV, n = 16).

Results

No significant differences were found in underlying disease and preoperative presentations, including operative risk among four groups. Overall in-hospital mortality was 22.4% (13 patients in Group I, 9 in Group II, 12 in Group III, and 1 in Group IV). New-onset stroke occurred in 15 patients postoperatively (3 patients [5.2%] in Group I, 3 [21.4%] in Group II, and 9 [26.5%] in Group III after excluding 36 patients with documented preoperative cerebrovascular accident or cerebral malperfusion). Root reconstruction and TAR were significantly associated with in-hospital mortality. TAR was significantly associated with surgery-related stroke. Compared to those in Group I, true lumen expansion and false lumen shrinkage during 1-year aortic remodeling were significantly higher in Groups III and IV. Both TAR and descending aorta stent grafting were significantly associated with decreased risk of patent false lumen.

Conclusions

Proximal aortic replacement remains the preferred surgical strategy for acute type I aortic dissection, with lower mortality and neurological complications. Proximal descending aorta stent grafting may benefit aortic remodeling, even without TAR.

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<![CDATA[Accuracy of Calcium Scoring calculated from contrast-enhanced Coronary Computed Tomography Angiography using a dual-layer spectral CT: A comparison of Calcium Scoring from real and virtual non-contrast data]]> https://www.researchpad.co/article/5c12cf78d5eed0c4849146bb

Purpose

Modern non-invasive evaluation of Coronary Artery Disease (CAD) requires non-contrast low dose Computed Tomography (CT) imaging for determination of Calcium Scoring (CACS) and contrast-enhanced imaging for evaluation of vascular stenosis. Several methods for calculation of CACS from contrast-enhanced images have been proposed before. The main principle for that is generation of virtual non-contrast images by iodine subtraction from a contrast-enhanced spectral CT dataset. However, those techniques have some limitations: Dual-Source CT imaging can lead to increased radiation exposure, and switching of the tube voltage (rapid kVp switching) can be associated with slower rotation speed of the gantry and is thus prone to motion artefacts that are especially critical in cardiac imaging. Both techniques cannot simultaneously acquire spectral data. A novel technique to overcome these difficulties is spectral imaging with a dual-layer detector. After absorption of the lower energetic photons in the first layer, the second layer detects a hardened spectrum of the emitted radiation resulting in registration of two different energy spectra at the same time. The objective of the present investigation was to evaluate the accuracy of virtual non-contrast CACS computed from spectral data in comparison to standard non-contrast imaging.

Methods

We consecutively investigated 20 patients referred to Coronary Computed Tomography Angiography (CCTA) with suspicion of CAD using a Dual-Layer spectral CT system (IQon; Philips Healthcare, The Netherlands). CACS was calculated from both, real- and virtual non-contrast images by certified software for medical use. Correlation analyses for real- and virtual non-contrast images and agreement evaluation with Bland-Altman-Plots were performed.

Results

Mean patient age was 57.7 ± 14 years (n = 20). 13 patients (65%) were male. Inter-quartile-range of clinical CACS was 0–448, the mean was 334. Correlation of CACS from real- and virtual non-contrast images was very high (0.94); p < 0.0001. The slope was 2.3 indicating that values from virtual non-contrast images are approximately half of the results obtained from real non-contrast data. Visual analysis of Bland-Altman-Plot shows good accordance of both methods when results from virtual non-contrast data are multiplied by the slope of the logistic regression model (2.3). The acquired power of this results is 0.99.

Conclusion

Determination of Calcium Score from contrast enhanced CCTA using spectral imaging with a dual-layer detector is feasible and shows good agreement with the conventional technique when a proportionality factor is applied. The observed difference between both methods is due to an underestimation of plaque volume, and—to an even greater extend -an underestimation of plaque density with the virtual non-contrast approach. Our data suggest that radiation exposure can be reduced through omitting additional native scans for patients referred to CCTA when using a dual-layer spectral system without the usual limitations of dual energy analysis.

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<![CDATA[Abdominal aortic calcification can predict all-cause mortality and CV events in dialysis patients: A systematic review and meta-analysis]]> https://www.researchpad.co/article/5bae98e840307c0c23a1c14d

Background

Abdominal aortic calcification (AAC) has a pretty high incidence in dialysis patients and may be associated with their prognosis. AAC can be assessed by abdominal CT or X-ray. We determined to investigate whether the occurrence of AAC is associated with all-cause mortality and cardiovascular (CV) events in dialysis patients through this meta-analysis and systematic review.

Methods

A comprehensive literature search was conducted using the PubMed, Cochrane library, Embase, Medline databases to collect cohort studies investigating whether AAC is associated with all-cause mortality and CV events of patients, and we also searched gray articles and conferences abstracts. Meta-analysis was performed by STATA software. Pooled results were expressed as hazard ratio (HR) with corresponding 95% confidence intervals (CI). Fixed-effect models were used to pool the HR of each trial.

Results

10 studies (2,724 dialysis patients) were identified. The presence of AAC was associated with increased risk for all-cause mortality among dialysis patients (HR, 2.84; 95% CI, 2.03–3.98; I2 = 9.8%; P = 0.354). Meanwhile, there was an association between AAC and increased risk for all CV events (fatal and non-fatal) in patients (HR, 2.04; 95% CI, 1.51–2.76, I2 = 44.6%; P = 0.125). 3 studies presented their endpoint as CV mortality, and the pooled HR was 2.46 (95%CI 1.38–4.40; I2 = 0.0%; P = 0.952).

There were also 2 studies that reported their primary endpoint as all-cause mortality and CV events, and the pooled HR was 5.72 (95% CI 3.24–10.10; I2 = 0.0%; P = 0.453).

Conclusions

Among patients treated with dialysis, AAC is associated with adverse outcomes, including all-cause mortality and CV events (fatal and non-fatal). The abdominal X-ray or CT scan can be used as a useful added method to evaluate the patient’s calcification. This may provide reasonable data for estimating the risk of adverse events in dialysis patients, which is helpful in guiding clinical treatment and improving the prognosis of dialysis patients.

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<![CDATA[Vasculoprotective Effects of 3-Hydroxybenzaldehyde against VSMCs Proliferation and ECs Inflammation]]> https://www.researchpad.co/article/5989daf3ab0ee8fa60bc1f34

3-hydroxybenzaldehyde (3-HBA) is a precursor compound for phenolic compounds like Protocatechuic aldehyde (PCA). From recent reports, PCA has shown vasculoprotective potency, but the effects of 3-HBA remain unclear. The aim of this study is to investigate the vasculoprotective effects of 3-HBA in endothelial cells, vascular smooth muscle cells and various animal models. We tested effects of 3-HBA in both vitro and vivo. 3-HBA showed that it prevents PDGF-induced vascular smooth muscle cells (VSMCs) migration and proliferation from MTS, BrdU assays and inhibition of AKT phosphorylation. It arrested S and G0/G1 phase of VSMC cell cycle in PI staining and it also showed inhibited expression levels of Rb1 and CD1. In human umbilical vein endothelial cells (HUVECs), 3-HBA inhibited inflammatory markers and signaling molecules (VCAM-1, ICAM-1, p-NF-κB and p-p38). For ex vivo, 3-HBA has shown dramatic effects in suppressing the sprouting from aortic ring of Spargue Dawley (SD) rats. In vivo data supported the vasculoprotective effects of 3-HBA as it inhibited angiogenesis from Matrigel Plug assay in C57BL6 mouse, prevented ADP-induced thrombus generation, increased blood circulation after formation of thrombus, and attenuated neointima formation induced by common carotid artery balloon injury of SD rats. 3-HBA, a novel therapeutic agent, has shown vasculoprotective potency in both in vitro and in vivo.

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<![CDATA[A New Animal Model for Investigation of Mechanical Unloading in Hypertrophic and Failing Hearts: Combination of Transverse Aortic Constriction and Heterotopic Heart Transplantation]]> https://www.researchpad.co/article/5989da30ab0ee8fa60b84181

Objectives

Previous small animal models for simulation of mechanical unloading are solely performed in healthy or infarcted hearts, not representing the pathophysiology of hypertrophic and dilated hearts emerging in heart failure patients. In this article, we present a new and economic small animal model to investigate mechanical unloading in hypertrophic and failing hearts: the combination of transverse aortic constriction (TAC) and heterotopic heart transplantation (hHTx) in rats.

Methods

To induce cardiac hypertrophy and failure in rat hearts, three-week old rats underwent TAC procedure. Three and six weeks after TAC, hHTx with hypertrophic and failing hearts in Lewis rats was performed to induce mechanical unloading. After 14 days of mechanical unloading animals were euthanatized and grafts were explanted for further investigations.

Results

50 TAC procedures were performed with a survival of 92% (46/50). When compared to healthy rats left ventricular surface decreased to 5.8±1.0 mm² (vs. 9.6± 2.4 mm²) (p = 0.001) after three weeks with a fractional shortening (FS) of 23.7± 4.3% vs. 28.2± 1.5% (p = 0.01). Six weeks later, systolic function decreased to 17.1± 3.2% vs. 28.2± 1.5% (p = 0.0001) and left ventricular inner surface increased to 19.9±1.1 mm² (p = 0.0001). Intraoperative graft survival during hHTx was 80% with 46 performed procedures (37/46). All transplanted organs survived two weeks of mechanical unloading.

Discussion

Combination of TAC and hHTx in rats offers an economic and reproducible small animal model enabling serial examination of mechanical unloading in a truly hypertrophic and failing heart, representing the typical pressure overloaded and dilated LV, occurring in patients with moderate to severe heart failure.

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<![CDATA[Inflammation and Vascular Effects after Repeated Intratracheal Instillations of Carbon Black and Lipopolysaccharide]]> https://www.researchpad.co/article/5989d9f7ab0ee8fa60b70774

Inflammation and oxidative stress are considered the main drivers of vasomotor dysfunction and progression of atherosclerosis after inhalation of particulate matter. In addition, new studies have shown that particle exposure can induce the level of bioactive mediators in serum, driving vascular- and systemic toxicity. We aimed to investigate if pulmonary inflammation would accelerate nanoparticle-induced atherosclerotic plaque progression in Apolipoprotein E knockout (ApoE-/-) mice. ApoE -/- mice were exposed to vehicle, 8.53 or 25.6 μg nanosized carbon black (CB) alone or spiked with LPS (0.2 μg/mouse/exposure; once a week for 10 weeks). Inflammation was determined by counting cells in bronchoalveolar lavage fluid. Serum Amyloid A3 (Saa3) expression and glutathione status were determined in lung tissue. Plaque progression was assessed in the aorta and the brachiocephalic artery. The effect of vasoactive mediators in plasma of exposed ApoE-/- mice was assessed in aorta rings isolated from naïve C57BL/6 mice. Pulmonary exposure to CB and/or LPS resulted in pulmonary inflammation with a robust influx of neutrophils. The CB exposure did not promote plaque progression in aorta or BCA. Incubation with 0.5% plasma extracted from CB-exposed ApoE-/- mice caused vasoconstriction in aorta rings isolated from naïve mice; this effect was abolished by the treatment with the serotonin receptor antagonist Ketanserin. In conclusion, repeated pulmonary exposure to nanosized CB and LPS caused lung inflammation without progression of atherosclerosis in ApoE-/- mice. Nevertheless, plasma extracted from mice exposed to nanosized CB induced vasoconstriction in aortas of naïve wild-type mice, an effect possibly related to increased plasma serotonin.

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<![CDATA[Selepressin and Arginine Vasopressin Do Not Display Cardiovascular Risk in Atherosclerotic Rabbit]]> https://www.researchpad.co/article/5989da59ab0ee8fa60b8f727

Background

Septic shock remains associated with significant mortality rates. Arginine vasopressin (AVP) and analogs with V1A receptor agonist activity are increasingly used to treat fluid-resistant vasodilatory hypotension, including catecholamine-refractory septic shock. Clinical studies have been restricted to healthy volunteers and catecholamine-refractory septic shock patients excluding subjects with cardiac co-morbidities because of presumed safety issues. The novel selective V1A receptor agonist selepressin, with short half-life, has been designed to avoid V2 receptor-related complications and long-term V1A receptor activation. Cardiovascular safety of selepressin, AVP, and the septic shock standard of care norepinephrine was investigated in a rabbit model of early-stage atherosclerosis.

Methods

Atherosclerosis was established in New Zealand White rabbits using a 1% cholesterol-containing diet. Selepressin, AVP, or norepinephrine was administered as cumulative intravenous infusion rates to atherosclerotic and non-atherosclerotic animals.

Results

Selepressin and AVP induced a slight dose-dependent increase in arterial pressure (AP) associated with a moderate decrease in heart rate, no change in stroke volume, and a moderate decrease in aortic blood flow (ABF). In contrast, norepinephrine induced a marked dose-dependent increase in AP associated with a lesser decrease in the heart rate, an increase in stroke volume, and a moderate increase in ABF. For all three vasopressors, there was no difference in responses between atherosclerotic and non-atherosclerotic animals.

Conclusion

Further studies should be considered using more advanced atherosclerosis models, including with septic shock, before considering septic shock clinical trials of patients with comorbidities. Here, selepressin and AVP treatments did not display relevant cardiovascular risk in early-stage rabbit atherosclerosis.

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<![CDATA[A mathematical model of aortic aneurysm formation]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdca9d

Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta, such that the diameter exceeds 3 cm. The natural history of AAA is progressive growth leading to rupture, an event that carries up to 90% risk of mortality. Hence there is a need to predict the growth of the diameter of the aorta based on the diameter of a patient’s aneurysm at initial screening and aided by non-invasive biomarkers. IL-6 is overexpressed in AAA and was suggested as a prognostic marker for the risk in AAA. The present paper develops a mathematical model which relates the growth of the abdominal aorta to the serum concentration of IL-6. Given the initial diameter of the aorta and the serum concentration of IL-6, the model predicts the growth of the diameter at subsequent times. Such a prediction can provide guidance to how closely the patient’s abdominal aorta should be monitored. The mathematical model is represented by a system of partial differential equations taking place in the aortic wall, where the media is assumed to have the constituency of an hyperelastic material.

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<![CDATA[Ablation of Potassium-Chloride Cotransporter Type 3 (Kcc3) in Mouse Causes Multiple Cardiovascular Defects and Isosmotic Polyuria]]> https://www.researchpad.co/article/5989da0cab0ee8fa60b78005

Inactivation of Kcc3 in a mixed 129/Sv×C57BL/6 mouse background has been previously found to increase systemic blood pressure (BP) through presumed neurogenic mechanisms. Yet, while this background is generally not considered ideal to investigate the cardiovascular system, KCC3 is also expressed in the arterial wall and proximal nephron. In the current study, the effects of Kcc3 ablation was investigated in a pure rather than mixed C57BL/6J background under regular- and high-salt diets to determine whether they could be mediated through vasculogenic and nephrogenic mechanisms. Aortas were also assessed for reactivity to pharmacological agents while isolated from the influence of sympathetic ganglia. This approach led to the identification of unforeseen abnormalities such as lower pulse pressure, heart rate, aortic reactivity and aortic wall thickness, but higher diastolic BP, left ventricular mass and urinary output in the absence of increased catecholamine levels. Salt loading also led systolic BP to be higher, but to no further changes in hemodynamic parameters. Importantly, aortic vascular smooth muscle cells and cardiomyocytes were both found to express KCC3 abundantly in heterozygous mice. Hence, Kcc3 inactivation in our model caused systemic vascular resistance and ventricular mass to increase while preventing extracellular fluid volume to accumulate. Given that it also affected the physiological properties of aortas in vitro, vasculogenic mechanisms could therefore account for a number of the hemodynamic abnormalities observed.

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<![CDATA[Endogenous Reference Genes for Gene Expression Studies on Bicuspid Aortic Valve Associated Aortopathy in Humans]]> https://www.researchpad.co/article/5989dac0ab0ee8fa60bb095b

Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality and predisposes patients to life-threatening aortic complications including aortic aneurysm. Quantitative real-time reverse transcription PCR (qRT-PCR) is one of the most commonly used methods to investigate underlying molecular mechanisms involved in aortopathy. The accuracy of the gene expression data is dependent on normalization by appropriate housekeeping (HK) genes, whose expression should remain constant regardless of aortic valve morphology, aortic diameter and other factors associated with aortopathy. Here, we identified an appropriate set of HK genes to be used as endogenous reference for quantifying gene expression in ascending aortic tissue using a spin column-based RNA extraction method. Ascending aortic biopsies were collected intra-operatively from patients undergoing aortic valve and/or ascending aortic surgery. These patients had BAV or tricuspid aortic valve (TAV), and the aortas were either dilated (≥4.5cm) or undilated. The cohort had an even distribution of gender, valve disease and hypertension. The expression stability of 12 reference genes were investigated (ATP5B, ACTB, B2M, CYC1, EIF4A2, GAPDH, SDHA, RPL13A, TOP1, UBC, YWHAZ, and 18S) using geNorm software. The most stable HK genes were found to be GAPDH, UBC and ACTB. Both GAPDH and UBC demonstrated relative stability regardless of valve morphology, aortic diameter, gender and age. The expression of B2M and SDHA were found to be the least stable HK genes. We propose the use of GAPDH, UBC and ACTB as reference genes for gene expression studies of BAV aortopathy using ascending aortic tissue.

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<![CDATA[Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression]]> https://www.researchpad.co/article/5989da43ab0ee8fa60b8ae9a

Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli. Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm (AAA) development. In addition, heme is known to strongly induce HO-1 expression. Utilizing the porcine pancreatic elastase (PPE) model of AAA induction in HO-1 heterozygous (HO-1+/-, HO-1 Het) mice, we found that a deficiency in HO-1 leads to augmented AAA development. Peritoneal macrophages from HO-1+/- mice showed increased gene expression of pro-inflammatory cytokines, including MCP-1, TNF-alpha, IL-1-beta, and IL-6, but decreased expression of anti-inflammatory cytokines IL-10 and TGF-beta. Furthermore, treatment with heme returned AAA progression in HO-1 Het mice to a wild-type profile. Using a second murine AAA model (Ang II-ApoE-/-), we showed that low doses of the HMG-CoA reductase inhibitor rosuvastatin can induce HO-1 expression in aortic tissue and suppress AAA progression in the absence of lipid lowering. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO-1. Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease.

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<![CDATA[Effects of p53-knockout in vascular smooth muscle cells on atherosclerosis in mice]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdc1d6

In vitro and in vivo evidence has indicated that the tumor suppressor, p53, may play a significant role in the regulation of atherosclerotic plaque formation. In vivo studies using global knockout mice models, however, have generated inconclusive results that do not address the roles of p53 in various cell types involved in atherosclerosis. In this study, we have specifically ablated p53 in vascular smooth muscle cells (VSMC) in the ApoE-/- mouse model to investigate the roles of p53 in VSMC in atherosclerotic plaque formation and stability. We found that p53 deficiency in VSMC alone did not affect the overall size of atherosclerotic lesions. However, there was a significant increase in the number of p53-/- VSMC in the fibrous caps of atherosclerotic plaques in the early stages of plaque development. Loss of p53 results in migration of VSMC at a faster rate using wound healing assays and augments PDGF-induced formation of circular dorsal ruffles (CDR), known to be involved in cell migration and internalization of surface receptors. Furthermore, aortic VSMC from ApoE-/- /p53-/- mice produce significantly more podosomes and are more invasive. We conclude that p53-/- VSMC are enriched in the fibrous caps of lesions at early stages of plaque formation, which is caused in part by an increase in VSMC migration and invasion as shown by p53-/- VSMC in culture having significantly higher rates of migration and producing more CDRs and invasive podosomes.

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<![CDATA[REM sleep deprivation induces endothelial dysfunction and hypertension in middle-aged rats: Roles of the eNOS/NO/cGMP pathway and supplementation with L-arginine]]> https://www.researchpad.co/article/5aafc743463d7e7d7e2e876d

Sleep loss can induce or aggravate the development of cardiovascular and cerebrovascular diseases. However, the molecular mechanism underlying this phenomenon is poorly understood. The present study was designed to investigate the effects of REM sleep deprivation on blood pressure in rats and the underlying mechanisms of these effects. After Sprague-Dawley rats were subjected to REM sleep deprivation for 5 days, their blood pressures and endothelial function were measured. In addition, one group of rats was given continuous access to L-arginine supplementation (2% in distilled water) for the 5 days before and the 5 days of REM sleep deprivation to reverse sleep deprivation-induced pathological changes. The results showed that REM sleep deprivation decreased body weight, increased blood pressure, and impaired endothelial function of the aortas in middle-aged rats but not young rats. Moreover, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) concentrations as well as endothelial NO synthase (eNOS) phosphorylation in the aorta were decreased by REM sleep deprivation. Supplementation with L-arginine could protect against REM sleep deprivation-induced hypertension, endothelial dysfunction, and damage to the eNOS/NO/cGMP signaling pathway. The results of the present study suggested that REM sleep deprivation caused endothelial dysfunction and hypertension in middle-aged rats via the eNOS/NO/cGMP pathway and that these pathological changes could be inhibited via L-arginine supplementation. The present study provides a new strategy to inhibit the signaling pathways involved in insomnia-induced or insomnia-enhanced cardiovascular diseases.

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<![CDATA[Ursodeoxycholic Acid (UDCA) Exerts Anti-Atherogenic Effects by Inhibiting RAGE Signaling in Diabetic Atherosclerosis]]> https://www.researchpad.co/article/5989dacfab0ee8fa60bb57fc

A naturally occurring bile acid, ursodeoxycholic acid (UDCA), is known to alleviate endoplasmic reticulum (ER) stress at the cellular level. However, the detailed action mechanisms of UDCA in atherosclerosis are not fully understood. In this study, we demonstrated whether UDCA exerts anti-atherogenic activity in diabetic atherosclerosis by targeting ER stress and “receptor for advanced glycation endproduct” (RAGE) signaling. UDCA markedly reduced ER stress, RAGE expression, and pro-inflammatory responses [including NF-κB activation and reactive oxygen species (ROS) production] induced in endothelial cells (ECs) by high glucose (HG). In particular, UDCA inhibited HG-induced ROS production by increasing the Nrf2 level. In macrophages, UDCA also blocked HG-induced RAGE and pro-inflammatory cytokine expression and inhibited foam cell formation via upregulation of the ATP-binding cassette (ABC) transporters, ABCA1 and ABCG1. In the diabetic mouse model, UDCA inhibited atheromatous plaque formation by decreasing ER stress, and the levels of RAGE and adhesion molecules. In conclusion, UDCA exerts an anti-atherogenic activity in diabetic atherosclerosis by targeting both ER stress and RAGE signaling. Our work implicates UDCA as a potential therapeutic agent for prevention or treatment of diabetic atherosclerosis.

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