Arteries Of Pigs Research Articles

Freezing and bioreactor in the low-concentration detergents: A novel approach in the decellularization of small-diameter arteries.

Using decellularized small-diameter vascular bypass substitutes (<6 mm) is an efficient method for bypass grafting. A solution containing 0.5% SDS (weight/volume) is commonly used for extended periods to generate acellular tissues. However, this solution causes damage to the microfibril structure and alters the mechanical forces. Hence, the objective of this study is to reduce the concentration of SDS to preserve the structure and achieve efficient decellularization. The study employs a diluted solution of 0.3% SDS (weight/volume) to treat fresh and frozen swine small-diameter arteries, utilizing physical methods such as freezing and thawing. The effectiveness of cell removal was evaluated using histological analysis and the remaining DNA content of the sample. Furthermore, the acellular circuit also assesses the cytotoxicity and proliferation of HUVECs to gauge their safety. Through the use of 0.3% SDS, a bioreactor system, and freezing-thawing, the pig arteries are successfully decellularized, resulting in residual DNA levels of less than 50 ng/mg dry weight. This process does not cause any major changes to the biomechanical or structural properties of the arteries. The acellular samples exhibit no toxicity on the L929 cell line and promote the growth of HUVECs at their highest rate on the fourth day. This allows for the placement of acellular vascular grafts to evaluate physiological processes within the animal body. This is an important requirement in clinical blood vessel transplantation.

Real time eye dose reduction in fluoroscopy with auditory and visual feedback dosimeter through swine model experiments

This paper proposes measurement and reduction of eye dose in real time for the physician and the assistant performing fluoroscopy guided arterial puncture. Eye dose rates were measured for 30 fluoroscopy-guided punctures of bilateral femoral arteries in pigs. Fifteen fluoroscopy-guided punctures were performed using real time radiation dosimeter without auditory and visual feedback and other fifteen punctures were done using real time radiation dosimeter with visual and auditory feedback worn on forehead by an interventional cardiologist having experience of more than 10 years. The mean radiation dose rate for eyes of physician during arterial puncturing with real time radiation dosimeter with auditory feedback was 0.07 mSv/h (n = 15) whereas it was 0.18 mSv/h (n = 15) without visual and auditory feedback. The percentage of reduction with the device was 61% for eyes. In case of assistant the reduction was 33% for eyes (n = 15). The real time visual and auditory feedback dosimeter has reduced the eye dose rate of the physician and assistant and also helped him staying away from the X-ray source. Real time radiation dosimeters can be an effective tool to measure and reduce the dose to the eyes. The radiation eye dose rate for physician and assistant was significantly reduced by using real time radiation dosimeter with visual and auditory feedback. The real time radiation dosimeter not only helps in measuring but also help in minimizing the radiation dose rate for the physician and assistant in real time.

Stable and Thin-Polymer-Based Modification of Neurovascular Stents with 2-Methacryloyloxyethyl Phosphorylcholine Polymer for Antithrombogenicity.

The advent of intracranial stents has revolutionized the endovascular treatment of cerebral aneurysms. The utilization of stents has rendered numerous cerebral aneurysm amenable to endovascular treatment, thereby obviating the need for otherwise invasive open surgical options. Stent placement has become a mainstream approach because of its safety and efficacy. However, further improvements are required for clinically approved devices to avoid the frequent occurrence of thrombotic complications. Therefore, controlling the thrombotic complications associated with the use of devices is of significant importance. Our group has developed a unique stent coated with a 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer. In this study, the surface characteristics of the polymer coating were verified using X-ray photoelectron spectroscopy and atomic force microscopy. Subsequently, the antithrombotic properties of the coating were evaluated by measuring platelet count and thrombin-antithrombin complex levels of whole human blood after 3 h of incubation in a Chandler loop model. Scanning electron microscopy was utilized to examine thrombus formation on the stent surface. We observed that MPC polymer-coated stents significantly reduced thrombus formation as compared to bare stents and several clinically approved devices. Finally, the coated stents were further analyzed by implanting them in the internal thoracic arteries of pigs. Angiographic imaging and histopathological examinations that were performed one week after implantation revealed that the vascular lumen was well maintained and coated stents were integrated within the vascular endothelium without inducing adverse effects. Thus, we demonstrated the efficacy of MPC polymer coating as a viable strategy for avoiding the thrombotic risks associated with neurovascular stents.

Abstract Mo032: Biofabrication of Small Vascular Graft using Human Amniotic Membrane

Vascular diseases encompass a spectrum of pathological conditions affecting blood vessels, including cerebrovascular disease, coronary heart disease, aneurysms, deep vein thrombosis, and peripheral arterial disease. In severe cases, surgical interventions such as bypass grafting or vascular replacement surgeries are necessary to restore blood flow by bypassing obstructed vessels with functional vascular substitutes. Autologous blood vessels harvested from patients are considered the gold standard for vascular surgeries. However, their availability is limited in patients with pre-existing chronic diseases or previous vessel harvest, and the associated morbidities of vessel harvesting and subsequent surgeries further restrict their therapeutic applicability. Synthetic grafts, including polytetrafluoroethylene (e-PTFE), polyethylene terephthalate (PET), and polyurethane (PU), have obtained FDA approval for clinical application and have shown satisfactory outcomes in large vessel surgeries (internal diameter &gt; 6mm). However, clinical trials targeting medium (6-10 mm) to small (&lt; 6mm) vessels often yield unsatisfactory results. This study aims to develop a small vascular graft using human amniotic membrane (HAM) that meets the structural, mechanical, and biological requirements for human vascular reconstructive surgeries. Fresh HAMs were decellularized with 1% Triton X-100 and 0.1% sodium dodecyl sulfate to prepare decellularized HAM (DAM). The DAM was trimmed into a rectangular shape and rolled around a catheter to prepare a tubular-shaped DAM vascular graft. After rolling, the DAM grafts were crosslinked with 1% genipin for 24 hours followed by thorough water washing. The final DAM vascular graft exhibited a multi-layered wall structure and comparable dimensions and mechanical properties to native arteries. The DAM vascular graft was further evaluated in vivo by replacing part of the rat abdominal aorta and part of the carotid artery in pigs. Both small and large animal studies demonstrated vascular patency with no neointimal hyperplasia (NIH), suggesting that the DAM graft holds significant promise as a small tissue-engineered vascular graft for future vascular reconstruction surgeries.

Pharmacological Gq inhibition induces strong pulmonary vasorelaxation and reverses pulmonary hypertension

Pulmonary arterial hypertension (PAH) is a life-threatening disease with limited survival. Herein, we propose the pharmacological inhibition of Gq proteins as a novel concept to counteract pulmonary vasoconstriction and proliferation/migration of pulmonary artery smooth muscle cells (PASMCs) in PAH. We demonstrate that the specific pan-Gq inhibitor FR900359 (FR) induced a strong vasorelaxation in large and small pulmonary arteries in mouse, pig, and human subjects ex vivo. Vasorelaxation by FR proved at least as potent as the currently used triple therapy. We also provide in vivo evidence that local pulmonary application of FR prevented right ventricular systolic pressure increase in healthy mice as well as in mice suffering from hypoxia (Hx)-induced pulmonary hypertension (PH). In addition, we demonstrate that chronic application of FR prevented and also reversed Sugen (Su)Hx-induced PH in mice. We also demonstrate that Gq inhibition reduces proliferation and migration of PASMCs in vitro. Thus, our work illustrates a dominant role of Gq proteins for pulmonary vasoconstriction as well as remodeling and proposes direct Gq inhibition as a powerful pharmacological strategy in PH.

Pulmonary 4D-flow MRI imaging in landrace pigs under rest and stress

4D-flow MRI is a promising technique for assessing vessel hemodynamics. However, its utilization is currently limited by the lack of reference values, particularly for pulmonary vessels. In this work, we have analysed flow and velocity in the pulmonary trunk (PT), left and right pulmonary arteries (LPA and RPA, respectively) in Landrace pigs at both rest and stress through the software MEVISFlow. Nine healthy Landrace pigs were acutely instrumented closed-chest and transported to the CMR facility for evaluation. After rest measurements, dobutamine was administered to achieve a 25% increase in heart rate compared to rest. 4D-flow MRI images have been analysed through MEVISFlow by two independent observers. Inter- and intra-observer reproducibility was quantified using intraclass correlation coefficient. A significant difference between rest and stress regarding flow and velocity in all the pulmonary vessels was observed. Mean flow increased 55% in PT, 75% in LPA and 40% in RPA. Mean peak velocity increased 55% in PT, 75% in LPA and 66% in RPA. A good-to-excellent reproducibility was observed in rest and stress for flow measurements in all three arteries. An excellent reproducibility for velocity was found in PT at rest and stress, a good one for LPA and RPA at rest, while poor reproducibility was found at stress. The current study showed that pulmonary flow and velocity assessed through 4D-flow MRI follow the physiological alterations during cardiac cycle and after stress induced by dobutamine. A clinical translation to assess pulmonary diseases with 4D-flow MRI under stress conditions needs investigation.

PVDF/ZnO piezoelectric nanofibers designed for monitoring of internal micro-pressure.

Organic piezoelectric materials are emerging as integral components in the development of advanced implantable self-powered sensors for the next generation. Despite their promising applications, a key limitation lies in their reduced mechanical force-to-electricity conversion efficiency. In this study, we present a breakthrough in the fabrication of soft poly(vinylidene fluoride) (PVDF) organic electrospun piezoelectric nanofibers (OEPNs) with exceptional piezoelectric performance achieved through the incorporation of zinc oxide nanorods (ZnO NR). The inclusion of ZnO NR proved instrumental in augmenting the nanocrystallization of PVDF organic electrospun piezoelectric nanofibers (OEPNs), leading to a highly efficient crystal phase transformation from the α phase to the β/γ phase, serving as superior piezoelectric working dipoles. The resulting PVDF/ZnO NR OEPNs exhibited unparalleled piezoelectric output voltage and current density, particularly noteworthy under a micro-pressure of 1 kPa and a low frequency of 1.5 Hz. Utilizing the obtained PVDF/ZnO NR OEPNs as the piezoelectric working element, we engineered a soft self-powered micro-pressure sensor. This sensor was implanted simultaneously on the cardiovascular walls of the heart and femoral artery in pigs. The sensor demonstrated precise monitoring and recording capabilities for micro-pressure changes during various physiological states, spanning from wakefulness to coma, euthanasia, and notably, the formation of cardiac thrombus. These findings underscore the immense potential of the implantable self-powered sensor for the assessment and diagnosis of pressure-related cardiovascular diseases, such as thrombus and atherosclerosis, during the postoperative recovery phase. This innovative technology offers valuable insights into the dynamic physiological states, paving the way for enhanced postoperative care and management of cardiovascular conditions.

Monolithic Integration of Ultraslim Flow Sensor and Medical Guidewire by Laser Filament Scanning Sintering for In Vivo Diagnostics of Cardiovascular Diseases.

In this study, an ultraslim thermal flow sensor system integrated onto a 340 μm diameter medical guidewire was developed using a laser filament scanning sintering method for the early diagnosis of cardiovascular diseases. The proposed system is a calorimetric-based micro thermal flow sensor comprising a microheater and two thermistors. Prior to fabrication, the sensor design was optimized through flow simulation, and the patterned sensor was successfully implemented on a thin and curved surface of the medical guidewire using a laser patterning method with Ag nanoparticles. The performance of the ultraslim thermal flow sensor-on-guidewire system (SoW) was evaluated under pulsatile flow by using an artificial heartbeat simulator with differentially induced fluid flow velocities of up to 60 cm/s. The resulting electrical signals generated by the temperature difference between the two thermistors caused by the fluid flow were measured across different velocity ranges. Based on the obtained data, a calibration curve was derived to establish the relationship between the fluid velocity and the sensor output voltage. Furthermore, the SoW was tested on living animals, whereby the measured blood flow velocities were 60-90 cm/s in the left coronary artery of pigs. This research demonstrates the potential of ultraslim microsensors, such as the developed thermal flow sensor system, for various industries, particularly in the medical field.

Abstract 16998: A Novel Preclinical Model of Calcified Coronary Chronic Total Occlusion

Introduction: These is significant research into the development of new medications and devices to treat chronic total occlusions (CTO). However, there is a lack of large animal models which reproduce the anatomy of clinical CTOs. Aim: Create an experimental model that mimics the anatomic features of human CTOs. Methods: CTOs were created in coronary arteries of live Yorkshire pigs (weight 80-120 lbs). The bioactive dental plug material (OsteoGen® Plug, Impladent Ltd) was implanted into the middle segment of one of coronary arteries (LAD, LCX or RCA). Angiography (C- Arm, Siemens) was performed before, immediately after plug implantation and before autopsy to confirm the presence of a CTO lesion. Animals were sacrificed at 9 hours to 3 months (n=12) and all coronary arteries underwent histopathological examination. Results: Histopathologic assessment confirmed that the bioactive plug composed of calcium apatite crystals and bovine collagen matrix mimics the pathological appearances of human CTOs. Serial histological sections showed complete resorption of the collagen matrix with replacement by fibrotic tissue 2 months after plug implantation, while the calcium content remains in the CTO. Conclusions: We have developed a reproducible model of calcified CTOs in pigs. Our model can provide a platform for evaluation of new drugs and devices for the treatment of calcified CTOs as well as to serve as a live model for training interventional cardiologists learning to cross CTOs.

FRI015 Single Nuclei Transcriptomics Of Epicardial Adipose Tissue From Female Pigs Reveals Differential Effects Of Endurance Exercise On Resident Innate And Adaptive Immune Cells

Abstract Disclosure: I. Ahmad: None. P. Faulkner: None. S. Gupta: None. D. Mullens: None. M. Thomas: None. S.P. Sytha: None. I. Ivan: None. J.J. Cai: None. C.L. Heaps: None. A.E. Newell-Fugate: None. Coronary artery disease (CAD) is the leading cause of global mortality. Although exercise training mitigates CAD progression, the mechanisms by which exercise training impacts epicardial adipose tissue (EAT) are unknown. We hypothesized that exercise training modulates EAT to promote an anti-inflammatory microenvironment in the coronary arteries of female pigs. Female Yucatan pigs (n=7) had an occluder placed around the proximal left circumflex artery. Eight-weeks postoperatively, pigs were assigned to sedentary or exercise groups with exercised pigs undergoing a 14-week treadmill running program. Upon termination, EAT was snap frozen. Bulk transcriptome sequencing was performed, and log fold change expression data was analyzed with Ingenuity Pathway Analysis. Microdroplet-based single nuclei transcriptome was analyzed using Seurat pipeline. Cell-cell interactome (CCI) analysis was performed using CellChat. Bulk RNA-sequencing revealed G-protein coupled receptor signaling, S100 family signaling, FAK signaling, and glutathione-mediated detoxification pathways were upregulated with exercise. Cellular movement, cell to cell communication, inflammatory response, and immune cell trafficking were predicted to be upregulated in exercised EAT. In adipocyte, B cell, and endothelial cell clusters, exercise induced upregulation of genes related to fatty acid synthesis and cellular metabolism. Exercise also caused upregulation of cell adhesion associated oncogene regulated and downregulation of S100 calcium binding protein A9 in B cells. By contrast, exercise caused downregulation of genes related to cell-cell adhesion and cellular metabolism in T cells. Although exercise increased macrophage numbers in EAT, macrophages displayed downregulation of genes related to protein folding and trafficking. Smooth muscle cells from exercised EAT showed upregulation of genes related to lipoprotein and glycogen turnover. CCI revealed increased interactions among all cell types in the insulin-like growth factor pathway of exercised EAT. By contrast, EAT from sedentary pigs had increased CCI for platelet derived growth factor (all cell types), galectin and WNT signaling (immune and mesenchymal cells), TGF (adipocytes, immune and mesenchymal cells), and VEGF (adipocytes, immune and endothelial cells). These findings suggest that exercise training downregulates genes related to cellular function in immune cells from both the innate (macrophages) and adaptive immune systems (T cells), but stimulates genes related to cellular metabolism and migration in B cells from EAT. CCI results suggest that sedentary EAT may secrete increased factors to stimulate inflammation, cell movement, and cell growth. These results provide a foundation for future functional studies of the effects of exercise on EAT and coronary artery regulation. Presentation: Friday, June 16, 2023

Synchrotron microtomography reveals insights into the degradation kinetics of bio-degradable coronary magnesium scaffolds

Bioresorbable magnesium scaffolds are a promising future treatment option for coronary artery stenosis, especially for young adults. Due to the degradation of these scaffolds (<1 year), long-term device-related clinical events could be reduced compared to treatments with conventional drug eluting stents. First clinical trials indicate a return of vasomotion after one year, which may be associated with improved long-term clinical outcomes. However, even after decades of development, the degradation process, ideal degradation time and biological response in vivo are still not fully understood.The present study investigates the in vivo degradation of magnesium scaffolds in the coronary arteries of pigs influenced by different strut thicknesses and the presence of antiproliferative drugs. Due to high 3D image contrast of synchrotron-based micro-CT with phase contrast (SR-μCT), a qualitative and quantitative evaluation of the degradation morphology of magnesium scaffolds was obtained. For the segmentation of the μCT images a convolutional network architecture (U-net) was exploited, demonstrating the huge potential of merging high resolution SR-μCT with deep learning (DL) supported data analysis.In total, 30 scaffolds, made of the rare earth alloy Resoloy®, with different strut designs were implanted into the coronary arteries of 10 domestic pigs for 28 days using drug-coated or uncoated angioplasty balloons for post-dilatation. The degradation morphology was analyzed using scanning electron microscopy, energy dispersive x-ray spectroscopy and SR-μCT. The data from these methods were then related to data from angiography, optical coherence tomography and histology.A thinner strut size (95 vs. 130 μm) and the presence of paclitaxel indicated a slower degradation rate at 28 d in vivo, which positively influences the late lumen loss (0.5 and 0.6 mm vs. 1.0 and 1.1 mm) and recoil values (0 and 1.7% vs. 6.1 and 22%).

Characterization of Green Fluorescent Protein in Heart Valves of a Transgenic Swine Model for Partial Heart Transplant Research.

A transgenic strain of pigs was created to express green fluorescent protein (GFP) ubiquitously using a pCAGG promoter. Here, we characterize GFP expression in the semilunar valves and great arteries of GFP-transgenic (GFP-Tg) pigs. Immunofluorescence was performed to visualize and quantify GFP expression and colocalization with nuclear staining. GFP expression was confirmed in both the semilunar valves and great arteries of GFP-Tg pigs compared to wild-type tissues (aorta, p = 0.0002; pulmonary artery, p = 0.0005; aortic valve; and pulmonic valve, p < 0.0001). The quantification of GFP expression in cardiac tissue allows this strain of GFP-Tg pigs to be used for future research in partial heart transplantation.

Identification of the Position of a Tethered Delivery Catheter to Retrieve an Untethered Magnetic Robot in a Vascular Environment.

In this paper, we propose a method of identifying the position of a tethered delivery catheter in a vascular environment, recombining an untethered magnetic robot (UMR) to the tethered delivery catheter, and safely retrieving them from the vascular environment in an endovascular intervention by utilizing a separable and recombinable magnetic robot (SRMR) and a magnetic navigation system (MNS). From images of a blood vessel and a tethered delivery catheter taken from two different angles, we developed a method of extracting the position of the delivery catheter in the blood vessel by introducing dimensionless cross-sectional coordinates. Then, we propose a retrieval method for the UMR by using the magnetic force considering the delivery catheter's position, suction force, and rotating magnetic field. We used thane MNS and feeding robot to simultaneously apply magnetic force and suction force to the UMR. In this process, we determined a current solution for generating magnetic force by using a linear optimization method. Finally, we conducted in vitro and in vivo experiments to verify the proposed method. In the in vitro experiment, which was in a glass tube environment, by using an RGB camera, we confirmed that the location of the delivery catheter in the glass tube could be recognized within an average error of 0.05 mm in each of the X- and Z-coordinates and that the retrieval success rate was greatly improved in comparison with that in the case without the use of magnetic force. In an in vivo experiment, we successfully retrieved the UMR in the femoral arteries of pigs.

Excitation and contraction of cardiac muscle and coronary arteries of brain-dead pigs.

Excitability and contraction of cardiac muscle from brain-dead donors critically influence the success of heart transplantation. Membrane physiology, Ca2+-handling, and force production of cardiac muscle and the contractile properties of coronary arteries were studied in hearts of brain-dead pigs. Cardiac muscle and vascular function after 12 h brain death (decapitation between C2 and C3) were compared with properties of fresh tissue. In both isolated cardiomyocytes (whole-cell patch clamp) and trabecular muscle (conventional microelectrodes), action potential duration was shorter in brain dead, compared to controls. Cellular shortening and Ca2+ transients were attenuated in the brain dead, and linked to lower mRNA expression of L-type calcium channels and a slightly lower ICa,L, current, as well as to a lower expression of phospholamban. The current-voltage relationship and the current above the equilibrium potential of the inward K+ (IK1) channel were altered in the brain-dead group, associated with lower mRNA expression of the Kir2.2 channel. Delayed K+ currents were detected (IKr, IKs) and were not different between groups. The transient outward K+ current (Ito) was not observed in the pig heart. Coronary arteries exhibited increased contractility and sensitivity to the thromboxane analogue (U46619), and unaltered endothelial relaxation. In conclusion, brain death involves changes in cardiac cellular excitation which might lower contractility after transplantation. Changes in the inward rectifier K+ channel can be associated with an increased risk for arrhythmia. Increased reactivity of coronary arteries may lead to increased risk of vascular spasm, although endothelial relaxant function was well preserved.

Percutaneous delivery and degradation of a shape memory elastomer poly(glycerol dodecanedioate) in porcine pulmonary arteries

Shape memory biodegradable elastomers are an emergent class of biomaterials well-suited for percutaneous cardiovascular repair requiring nonlinear elastic materials with facile handling. We have previously developed a chemically crosslinked shape memory elastomer, poly (glycerol dodecanedioate) (PGD), exhibiting tunable transition temperatures around body temperature (34–38 °C), exhibiting nonlinear elastic properties approximating cardiac tissues, and favorable degradation rates in vitro. Degree of tissue coverage, degradation and consequent changes in polymer thermomechanical properties, and inflammatory response in preclinical animal models are unknown material attributes required for translating this material into cardiovascular devices. This study investigates changes in the polymer structure, tissue coverage, endothelialization, and inflammation of percutaneously implanted PGD patches (20 mm × 9 mm x 0.5 mm) into the branch pulmonary arteries of Yorkshire pigs for three months. After three months in vivo, 5/8 samples exhibited (100%) tissue coverage, 2/8 samples exhibited 85–95% tissue coverage, and 1/8 samples exhibited limited (<20%) tissue coverage with mild-moderate inflammation. PGD explants showed a (60–70%) volume loss and (25–30%) mass loss, and a reduction in polymer crosslinks. Lumenal and mural surfaces and the cross-section of the explant demonstrated evidence of degradation. This study validates PGD as an appropriate cardiovascular engineering material due to its propensity for rapid tissue coverage and uneventful inflammatory response in a preclinical animal model, establishing a precedent for consideration in cardiovascular repair applications.

Abstract 14778: Combined Shear Stress-Molecular Imaging for the Evaluation of Early Arterial Healing Responses Following Implantation of Bioresorbable Scaffold With Different Strut Thickness

Introduction and Hypothesis: Arterial healing following stent implantation involves a series of biological reactions such as thrombosis, inflammation, neointimal regeneration. Clinical evidences have shown favorable arterial healing after thin-strut stents, however, there has been a lack of in vivo imaging evidence on how strut thickness affect vascular healing process. We evaluated local endothelial shear stress (ESS) and healing response of a thin-strut bioresorbable scaffold (BRS, 100μm) compared to first-generation 157μm-thickness ABSORB. Methods and Results: BRS and ABSORB were simultaneously implanted in left coronary arteries of the same pigs (n=7). Detailed scaffolded-artery 3D model was reconstructed based on OCT and angiography. Scaffold-related inflammation response was serially assessed by dual-modal OCT-near-infrared fluorescence (OCT-NIRF) molecular imaging using macrophage-mannose receptor-Cy7 as an inflammation-targeting agent. On ESS analysis, regions with athero-prone low ESS were significantly greater in thick-ABSORB compared to BRS. Dual-modal OCT-NIRF imaging visualized arterial inflammation activity at peri-strut regions in vivo (Figure). Based on coregistered ESS-NIRF data, we found a significant inverse correlation was found between ESS and NIRF activity (p&lt;0.0001), suggesting immune-modulating effect of ESS during early stent healing phase. Arterial inflammation, quantified as target-to-background ratio, was significantly lower in thin-strut BRS than ABSORB at 2 weeks (p&lt;0.01). At week 3, unlike ABSORB with residual peri-strut NIRF signals, inflammation activity dissipated significantly in BRS. Ex vivo confocal fluorescence microscopy (Figure) and immunohistochemical analysis well corroborated the findings in vivo . Conclusions: Thin-strut BRS was associated with less inflammation and rapid resolution of inflammation compared to thicker-strut ABSORB. This study provides in vivo imaging insights into how strut thickness affects early arterial healing and the importance of ESS as an inflammatory modulator. Our comprehensive imaging strategy enabling evaluation of complex interplay between scaffold, ESS, and artery is expected to enhance understanding of stent healing.

Research on the Distribution of Coronary Arteries in Pig (Sus Scrofa Domesticus)

Pigs are some of the most widely used experimental models, an advantage being the characteristics of homeostasis and many morphological features comparable to those in humans. For this reason, we addressed this topic in this paper, with the major objective of completing the data and even identifying some features not described in the literature. The present study was performed on 20 pig carcasses, with different weights and ages (2-4 months). The aim was to highlight some peculiarities regarding the coronary artery system in this species, using as a method the injection of vessels with contrasting plastic material. The collaterals and terminals of the coronary arteries, their distribution territories as well as the identified individual variants were described. As a general conclusion, regardless of the polymorphism in all dissected cases, the left coronary artery was the dominant artery, there being no exception from the data known in the literature.

Negative-pressure-assisted ventilation lowers driving pressure and mechanical power in an ARDS model.

Increased lung heterogeneity from regional alveolar collapse drives ventilator-induced lung injury in patients with acute respiratory distress syndrome (ARDS). New methods of preventing this injury require study. Our study objective was to determine whether the combination of temporary transvenous diaphragm neurostimulation (TTDN) with standard-of-care volume-control mode ventilation changes lung mechanics, reducing ventilator-induced lung injury risk in a preclinical ARDS model. Moderate ARDS was induced using oleic acid administered into the pulmonary artery in pigs, which were ventilated for 12 h postinjury using volume-control mode at 8 mL/kg, positive end-expiratory pressure (PEEP) 5 cmH2O, with respiratory rate and [Formula: see text] set to achieve normal arterial blood gases. Two groups received TTDN, either every second breath [mechanical ventilation (MV) + TTDN50%, n = 6] or every breath (MV + TTDN100%, n = 6). A third group received volume-control ventilation only (MV, n = 6). At study-end, [Formula: see text]/[Formula: see text] was highest and alveolar-arterial oxygen (A-a) gradient was lowest for MV + TTDN100% (P < 0.05). MV + TTDN100% had the smallest end-expiratory lung volume loss and lowest extravascular lung water at study-end (P < 0.05). Static lung compliance was highest and transpulmonary driving pressure was lowest at baseline, postinjury, and study-end in MV + TTDN100% (P < 0.05). The total exposure to transpulmonary driving pressure, mechanical power, and mechanical work was the lowest in MV + TTDN100% (P < 0.05). Lung injury score and total inflammatory cytokine concentration in lung tissue were the lowest in MV + TTDN100% (P < 0.05). Volume-control ventilation plus transvenous diaphragm neurostimulation on every breath improved [Formula: see text]/[Formula: see text], A-a gradient, and alveolar homogeneity, as well as reduced driving pressure, mechanical power, and mechanical work, and resulted in lower lung injury scores and tissue cytokine concentrations in a preclinical ARDS model.NEW & NOTEWORTHY Combining temporary transvenous diaphragm neurostimulation with volume-control ventilation on every breath, called negative-pressure-assisted ventilation, improved gas exchange and alveolar homogeneity in a preclinical model of moderate ARDS. Transpulmonary driving pressure, mechanical power, and mechanical work reductions were observed and resulted in lower lung injury scores and tissue cytokine concentrations in the every-breath-neurostimulation group compared with volume-control ventilation only. Negative-pressure-assisted ventilation is an exciting new potential tool to reduce ventilator-induced lung injury in patients with ARDS.

Abstract P245: Catheter-based Radiofrequency Renal Denervation In Normotensive Pigs Leads To Long-term Pathological Changes In Renal Nerves

Objective: Pre-clinical data of renal nerve regrowth following radiofrequency (RF) renal denervation (RDN) are lacking. In this analysis of RF RDN in normotensive pigs, we assessed the specificity and durability of RF ablation to the perivascular tissues around the renal arteries. Design and Method: RF ablations were delivered to the renal arteries in pigs. To assess specificity, serial tissue samples were harvested from 6 pigs at day 7, and 8 pigs at day 28. Surrounding tissues (ureter, kidney, lymph nodes, skeletal muscle, adrenal glands, and renal nerves) were evaluated with a semi-quantitative scoring system ( Figure ). To assess durability, RF RDN was performed in a separate group of pigs with an additional control group. Serial tissue examination at day 7 (n=6 animals per group) and day 180 (n=8 per group) included quantification of cortical norepinephrine (NE) levels and renal cortical axon density, and evaluation for fibrosis, necrosis, and nerve fiber atrophy. Results: Disruption to non-target perivascular tissues was rare, whereas artery nerve disruption and axonal loss were sustained through 28 days ( Figure ). At 180 days, there was nerve atrophy from axonal destruction around the ablation regions. Necrosis was evident at day 7 but not day 180. Fibrosis was confined to the ablated regions. Renal cortical axon density and cortical NE levels were significantly reduced at 7 and 180 days in the RDN group vs. control. Conclusion: RF RDN specifically disrupted the renal nerves leading to axonal loss. Cortical axon density, NE reduction, and nerve atrophy were sustained through 180 days. These results support the existing clinical evidence of the specificity and durability of RF RDN.

A wireless millimetric magnetoelectric implant for the endovascular stimulation of peripheral nerves

Implantable bioelectronic devices for the simulation of peripheral nerves could be used to treat disorders that are resistant to traditional pharmacological therapies. However, for many nerve targets, this requires invasive surgeries and the implantation of bulky devices (about a few centimetres in at least one dimension). Here we report the design and in vivo proof-of-concept testing of an endovascular wireless and battery-free millimetric implant for the stimulation of specific peripheral nerves that are difficult to reach via traditional surgeries. The device can be delivered through a percutaneous catheter and leverages magnetoelectric materials to receive data and power through tissue via a digitally programmable 1 mm × 0.8 mm system-on-a-chip. Implantation of the device directly on top of the sciatic nerve in rats and near a femoral artery in pigs (with a stimulation lead introduced into a blood vessel through a catheter) allowed for wireless stimulation of the animals’ sciatic and femoral nerves. Minimally invasive magnetoelectric implants may allow for the stimulation of nerves without the need for open surgery or the implantation of battery-powered pulse generators.