Swine Artery Research Articles

Abstract No. 163 Feasibility of pancreatic particle embolization: a proof of safety study in a porcine model

Although particle embolization is a common treatment of hypervascular neuroendocrine metastases of the liver, this treatment is not considered an option for the originating pancreatic neuroendocrine tumor(s) due to theoretical concern for pancreatitis. The purpose of this study was to explore the safety of pancreatic embolization in a porcine model. Approval for this study was obtained from the Institutional Animal Care and Use Committee. A total of 6 domestic swine weighing between 90 and 110 pounds were obtained. A single nonsurvival animal underwent infusion of methylene blue dye into the dorsal pancreatic artery using a microcatheter followed by particle embolization to stasis using 100-300 μm Embosphere particles to confirm technical feasibility. Immediate laparotomy confirmed blue staining of pancreatic parenchyma without evidence of non-target embolization. Five survival animals underwent baseline serum lipase level assay, and particle embolization of the dorsal pancreatic artery was performed under general anesthesia. Animals were observed postoperatively for one week with monitoring of behavior, activity, food intake, and observation for signs of pancreatitis. After one week, repeat serum lipase was obtained, the animals were euthanized, and their pancreata excised for gross pathologic analysis. Technical success with embolization was achieved in all study animals. In the five survival animals that were monitored after embolization, behavior, activity levels and food intake returned to baseline by postoperative day #1. All animals survived to 7 days without signs or symptoms of significant pain, systemic infection or decline. There was no significant change in serum lipase levels comparing pre-procedure to day 7, with average serum lipase levels of 56.8 U/L and 40.2 U/L, respectively. At necropsy, regions of lobular expansion and discoloration were identified in all pancreata that are compatible with inflammation. These findings suggest that particle embolization of the dorsal pancreatic artery in swine is technically feasible and results in adequate ischemia to cause inflammation of target pancreatic tissues, but without biochemical signs of pancreatitis, systemic sequelae, or mortality after one week of observation. Based on this early data, further evaluation of particle embolization of the pancreas in animal models may be justified to further clarify safety and physiologic sequelae.

Downstream Paclitaxel Released Following Drug-Coated Balloon Inflation and Distal Limb Wound Healing in Swine

The authors evaluated the presence of paclitaxel and healing of distal hind limb wounds created in 27 swine using biopsy punches followed by paclitaxel-coated balloon (PCB) use in the iliofemoral arteries of healthy swine. After 14 and 28days, no differences were seen in time course, appearance, and histopathology of wound healing between the single or triple PCB and uncoated balloon treatment despite clinically relevant paclitaxel concentrations in the skin adjacent to the healing wounds. Presence of paclitaxel downstream from the PCB treatment site does not impair the wound healing response of preexisting distal cutaneous lesions in healthy swine.

Abstract P495: Aqua Embolic System: Evaluating the Performance of a New Liquid Embolic System Using a Swine AVM Model

Introduction: Liquid embolic material (LEM) plays an essential role in the treatment of hemorrhagic stroke caused by vascular malformation such as arteriovenous malformations (AVMs). However, currently available non-adhesive LEMs has the problem of catheter entrapment, and also known to have cytotoxicity due to the organic solvents such as Dimethyl Sulfoxide (DMSO). Aqua Embolic System (AES) is a new liquid embolic material, which is mainly composed of multiple polysaccharides. AES, when injected via a microcatheter, immediately forms a solid and elastic hydrogel cast upon exposure to Ca2+ in the bloodstream. The use of organic solvents, e.g., DMSO, is not required. The performance of AES was evaluated using an established AVM model utilizing swine rete-mirabile. Methods: Under general anesthesia, the left ascending pharyngeal artery (APA) of Yorkshire swine (40 kg) was catheterized using a microcatheter (ID:0.013 inches), and AES was slowly injected into the rete-mirabile under fluoroscopy. The following parameters were assessed to evaluate the embolization performance of the AES; 1) the amount of AES required for the complete occlusion of the feeding artery, 2) injection speed, 3) radiopacity during the deployment, and 4) incidence of catheter entrapment after the injection. The same evaluation was performed on the contralateral rete-mirabile and the left renal artery as well. Results: 12 arteries in 4 swine were treated, and all arteries were completely occluded without technical complications. The injected materials immediately formed AES cast in all vessels, followed by the reflux over the tip of the microcatheter. All catheters were withdrawn without any sign of catheter entrapment. The AES mixed with tantalum based contrasts medium showed sufficient radiopacity under fluoroscopy. With the injection speed of 0.02ml/sec, the average volume required was 0.85mL for the APA and 2.9mL for the renal artery. No increased thrombogenicity or vasospasm near the treated lesion was observed during the procedure. Conclusions: AES, which is a DMSO free, non-adhesive polysaccharides-based LEM, may be used as an embolic material for the treatment of hemorrhagic stroke caused by cerebrovascular diseases, such as brain AVM.

A novel rabbit thromboembolic occlusion model

BackgroundTo develop a preclinical thromboembolic occlusion model for studying revascularization strategies.MethodsClot analog with barium sulfate was injected into the distal aorta in 9 New Zealand white rabbits. The situation of...

Mechanically tuned vascular graft demonstrates rapid endothelialization and integration into the porcine iliac artery wall

Mechanical properties of vascular grafts likely play important roles in healing and tissue regeneration. Healthy arteries are compliant at low pressures but stiffen rapidly with increasing load, ensuring sufficient volumetric expansion without overstretching the vessel. Commercial synthetic vascular grafts are stiff and unable to expand under physiologic loads, which may result in altered hemodynamics, deleterious cellular responses, and compromised clinical performance. The goal of this study was to develop an Elastomeric Nanofibrillar Graft (ENG) with artery-tuned nonlinear compliance and compare its healing responses to conventional expanded polytetrafluoroethylene (ePTFE) grafts in a porcine iliac artery model. Human and porcine iliac arteries were mechanically characterized, and an ENG with similar properties was created by utilizing residual strains within electrospun nanofibers. The ENG was tested for implantation suitability and implanted onto n = 5 domestic swine iliac arteries, with control ePTFE grafts implanted onto the contralateral iliac arteries. After two weeks in vivo, all iliac arteries and grafts remained patent with no signs of thrombosis or dilation. The mechanically tuned ENG implants exhibited a more confluent CD31-positive cell monolayer (1.53 ± 0.73 µm2/mm vs 0.52 ± 0.55 µm2/mm, p = 0.042) on the graft lumenal surface and a higher fraction of αSMA-positive cells (16.2 ± 8.6% vs 1.4 ± 0.7%, p = 0.018) within the graft wall than the ePTFE controls. Despite heavy cellular infiltration, the ENG retained its artery-like mechanical characteristics after two weeks in vivo. These short-term results demonstrate potential advantages of mechanically tuned biomimetic vascular grafts over standard ePTFE grafts. Statement of SignificanceOff-the-shelf synthetic vascular grafts are often the only option available for treating advanced stages of vascular disease. Despite significant efforts devoted to improving their biochemical characteristics, synthetic peripheral arterial grafts continue to demonstrate poor clinical outcomes leading to costly reinterventions. Here, we hypothesized that a synthetic vascular graft with elastomeric mechanical properties tuned to a healthy peripheral artery promotes better healing responses than a synthetic stiff graft. To test this hypothesis, we developed an Elastomeric Nanofibrillar Graft (ENG) with artery-tuned mechanical properties and compared its performance to a commercial ePTFE graft in a preclinical porcine iliac artery model. Our results suggest that mechanically tuned ENGs can offer better healing responses, potentially leading to better clinical outcomes for peripheral arterial repairs.

Cellulose fibers-reinforced self-expanding porous composite with multiple hemostatic efficacy and shape adaptability for uncontrollable massive hemorrhage treatment

Uncontrollable hemorrhage leads to high mortality and thus effective bleeding control becomes increasingly important in the military field and civilian trauma arena. However, current hemostats not only present limitation when treating major bleeding, but also have various side effects. Here we report a self-expanding porous composites (CMCP) based on novel carboxymethyl cellulose (CMC) fibers and acetalized polyvinyl alcohol (PVA) for lethal hemorrhage control. The CMC fibers with uniform fibrous structure, high liquid absorption and procoagulant ability, are evenly interspersed inside the composite matrix. The obtained composites possess unique fiber-porous network, excellent absorption capacity, fast liquid-triggered self-expanding ability and robust fatigue resistance, and their physicochemical performance can be fine-tuned through varying the CMC content. In vitro tests show that the porous composite exhibits strong blood clotting ability, high adhesion to blood cells and protein, and the ability to activate platelet and the coagulation system. In vivo hemostatic evaluation further confirms that the CMCP presents high hemostatic efficacy and multiple hemostatic effects in swine femoral artery major hemorrhage model. Additionally, the CMCP will not fall off from the injury site, and is also easy to surgically remove from the wound cavity after the hemostasis. Importantly, results of CT tomography and 3D reconstruction indicate that CMCP can achieve shape adaptation to the surrounding tissues and the wound cavities with different depths and shapes, to accelerate hemostasis while protecting wound tissue and preventing infection.

Inhibition of edge stenosis of endografts in swine iliac arteries by a novel endograft with biodegradable coating at both ends

ObjectiveThis study evaluated the effectiveness and safety of a novel endograft with a biodegradable coating at both ends in preventing edge stenosis in swine iliac arteries. The biodegradable coating was composed of polylactide and paclitaxel. MethodsFour types of endograft were implanted in the iliac arteries of healthy swine: an endograft without coating (control group) and endografts with polylactide and paclitaxel coating containing 0.1, 0.3, or 3.6 μg/mm2 of paclitaxel. The edge stenosis of these endografts in swine iliac arteries was assessed using angiographic image data at 30, 90, and 180 days after the operation. After terminal angiography, histologic evaluation of the treated arteries was performed. The treated sections of iliac arteries and blood samples were obtained at 1, 7, 30, 90, and 180 days for pharmacokinetic analysis. ResultsThe results of angiographic and histologic evaluation demonstrated that intimal hyperplasia contributed to edge stenosis and polylactide-paclitaxel coating effectively inhibited edge stenosis. At 30 days, edge stenosis was observed at both the proximal and distal edges of the endograft without coating. At 90 days, edge stenosis was detected for the endograft coated with 0.1 μg/mm2 paclitaxel, and ectasia dilation occurred at the proximal and distal edges of the endograft coated with 3.6 μg/mm2 paclitaxel. No edge stenosis or other adverse effects were observed at 90 and 180 days for the endograft coated with 0.3 μg/mm2 paclitaxel. In addition, for the endograft coated with 0.3 μg/mm2 paclitaxel, a pharmacokinetic analysis showed that the paclitaxel concentration of treated segments decreased from 14 264 ± 1020 ng/g at day 1 to 80 ± 70 ng/g at day 90, and 20 ± 40 ng/g at day 180. The plasma paclitaxel concentration was low at day 1 and no longer detected after 7 days. ConclusionsPolylactide and paclitaxel coating containing 0.3 μg/mm2 paclitaxel at both ends of endografts effectively and safely inhibits edge stenosis in swine iliac arteries.

Blood-Derived Biomaterial for Catheter-Directed Arterial Embolization.

Vascular embolization is a life-saving minimally invasive catheter-based procedure performed to treat bleeding vessels. Through these catheters, numerous metallic coils are often pushed into the bleeding artery to stop the blood flow. While there are numerous drawbacks to coil embolization, physician expertise, availability of these coils, and their costs further limit their use. Here, a novel blood-derived embolic material (BEM) with regenerative properties, that can achieve instant and durable intra-arterial hemostasis regardless of coagulopathy, is developed. In a large animal model of vascular embolization, it is shown that the BEM can be prepared at the point-of-care within 26 min using fresh blood, it can be easily delivered using clinical catheters to embolize renal and iliac arteries, and it can achieve rapid hemostasis in acutely injured vessels. In swine arteries, the BEM increases cellular proliferation, angiogenesis, and connective tissue deposition, suggesting vessel healing and durable vessel occlusion. The BEM has significant advantages over embolic materials used today, making it a promising new tool for embolization.

Electrical stimulation mapping of the pulmonary artery in swine: impact on pulmonary artery denervation procedure for pulmonary hypertension

Abstract Introduction Pulmonary artery denervation (PAD) has been recently shown to decrease pulmonary artery (PA) pressure. However, there is a lack of data related to target sites for ablation. Purpose To determine the optimal PA ablation sites based on response to high-frequency stimulation mapping and anatomical areas where radiofrequency ablation (RFA) should be avoided due to the risk of severe collateral damage. Methods A total of 17 Landrace swines were included into the study. PA angiography, hemodynamic measurements by right heart-sided catheterization and electrophysiological mapping (EM) using low (cycle length 330 ms) and high-frequency (33Hz) stimulation (HFS). Stimulation was performed at PA bifurcation and proximal parts of the main PA branches with a 5-mm distance between points; catheter manipulation was performed under fluoroscopic guidance in multiple projections. Points with evoked reactions were tagged on a 3-dimentional PA model in each case. In order to confirm reproducibility of reactions, HFS was performed at least twice at each point with a response. PA models obtained from all animals were combined in one for the final analysis. RFA using an open-irrigated catheter (40 Watts; 40 s; irrigation 30 ml/min) were performed at sites with evoked reactions. Repeated HFS was performed at ablation sites. After the procedure all animals were euthanized and underwent an autopsy study. Results Low-frequency stimulation (LFS) allowed to define areas of ventricular capture (VC) where HFS was avoided due to ventricular fibrillation induction risk. During HFS the following evoked responses were documented: sinus bradycardia, sinus rhythm (SR) acceleration, phrenic nerve capture (PNC), and laryngeal recurrent nerve capture. HFS captured left and right phrenic nerves in all animals at PA trunk, and its course was tagged (Figure 1). Laryngeal recurrent nerve capture was found in 4 (23%) of animals. Atrial capture was found in all cases while LFS at the anterior aspects of both PAs even at low output, and this precluded evaluation of neural autonomic reactions in these areas. Evoked bradycardia and SR acceleration were both found during HFS in 10 (59%) of cases each. Following RFA application evoked reactions were non-reproducible in all cases. RFA was applied in areas where no PNC or VC points were observed. An autopsy study confirmed the presence of RF-induced lesions of the PA wall. Conclusions There are two important findings of our study. First, stimulation-guided PA mapping is feasible and reveals several specific responses to HFS. Ablation at points with responses leads to non-reproducibility of the evoked reactions, confirming that transcatheter RFA may be an adequate approach for PA denervation. Second, previously proposed circular PA ablation might be associated with phrenic and laryngeal recurrent nerve damage. Stimulation-guided PA denervation can be proposed as a safer procedure, and should be evaluated in clinical settings. Figure 1. PA schematic representation Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Russian Foundation for Basic Research

TCT CONNECT-362 Natural Vascular Scaffolding Therapy Shows Favorable Biocompatibility and Protection of Elastin Content in Comparison to Balloon Angioplasty and Stent in Peripheral Arteries of LDLR-Knockout Hypercholesterolemic Swine

TCT CONNECT-362 Natural Vascular Scaffolding Therapy Shows Favorable Biocompatibility and Protection of Elastin Content in Comparison to Balloon Angioplasty and Stent in Peripheral Arteries of LDLR-Knockout Hypercholesterolemic Swine

Handling and performance characteristics of a new small caliber radiopaque embolic microsphere.

The in vitro and in vivo handling and performance characteristics of a small caliber radiopaque embolic microsphere, 40–90 μm DC Bead LUMI™ (LUMI40‐90), were studied. Microsphere drug loading and elution and effects on size, suspension, and microcatheter delivery were evaluated using established in vitro methodologies. In vivo evaluations of vascular penetration (rabbit renal artery embolization), long‐term biocompatibility and X‐ray imaging properties, pharmacokinetics and local tissue effects of both doxorubicin (Dox) and irinotecan (Iri) loaded microspheres (swine hepatic artery embolization) were conducted. Compared to 70–150 μm DC Bead LUMI (LUMI70‐150), LUMI40‐90 averaged 70 μm versus 100 μm, which was unchanged upon drug loading. Handling, suspension, and microsphere delivery studies were successfully performed. Dox loading was faster (20 min) and Iri equivalent (<10 min) while drug elution rates were similar. Contrast suspension times were longer with no delivery complications. Vascular penetration was statistically greater (rabbit) with no unexpected adverse safety findings (swine). Microspheres ± drug were visible under X‐ray imaging (CT) at 90 days. Peak plasma drug levels and area under the curve were greater for LUMI40‐90 compared to LUMI70‐150 but comparable to 70–150 μm DC BeadM1™ (DC70‐150). Local tissue effects showed extensive hepatic necrosis for Dox, whereas Iri displayed lower toxicity with more pronounced lobar fibrosis. LUMI40‐90 remains suspended for longer and have greater vessel penetration compared to the other DC Bead LUMI sizes and are similarly highly biocompatible with long‐term visibility under X‐ray imaging. Drug loading is equivalent or faster with pharmacokinetics similar to DC70‐150 for both Dox and Iri.

Exercise Training Restores K+ Channel Contributions to Hydrogen Peroxide‐Mediated Dilation Independent of PKG Dimerization in Collateral‐Dependent Coronary Arterioles

In coronary artery disease (CAD), the ability of the coronary circulation to deliver blood to meet oxygen demands of the heart is often impaired. Exercise training has been established to mitigate the negative effects of CAD by preserving reactivity of the coronary microcirculation. We have previously reported that exercise increases the contribution of hydrogen peroxide (H2O2) to enhanced endothelium‐dependent vasodilation in collateral‐dependent coronary arterioles. Others have shown that cGMP‐dependent protein kinase (PKG) can be activated via oxidation by H2O2, inducing dimer formation. The PKG dimer has been shown to act on substrates, such as K+ channels, to contribute to vascular smooth muscle relaxation and vasodilation. In the current study, we tested the hypothesis that exercise training‐enhanced H2O2‐induced vasodilation is mediated through enhanced PKG dimerization and subsequent activation of Kv and BKca channels in coronary arterioles isolated from ischemic myocardium. An ameroid occluder was surgically placed on the proximal left circumflex coronary artery of female Yucatan miniature swine to induce gradual occlusion while the left anterior descending artery was left unoccluded to serve as a control. Eight weeks postoperatively, pigs were assigned to sedentary (n=14) or exercise training (n=13; progressive treadmill training for 13 weeks) regimens. Coronary arterioles (75–150 μm) and small arteries (250–400 um) were isolated from myocardium of the left circumflex and left anterior descending regions. Immunoblot analysis indicated that H2O2 induced PKG dimer formation in both porcine coronary arterioles and small arteries. Chronic coronary artery occlusion appeared to diminish H2O2‐mediated PKG dimer formation in collateral‐dependent arterioles and the reduced dimerization persisted with exercise training. H2O2‐mediated vasodilation tended to be impaired in arterioles isolated from the collateral‐dependent regions of sedentary pigs and was partially restored with exercise training. It also appears that both Kv and BKCa channels contributed to H2O2‐mediated dilation after exercise training. Our data demonstrate that H2O2 stimulates PKG dimer formation in both porcine coronary arterioles and small arteries. Contrary to our hypothesis, H2O2‐induced PKG dimerization is not enhanced by exercise training in either nonoccluded or collateral‐dependent arterioles. However, both Kv and BKCa channels appear to contribute to exercise training‐enhanced H2O2‐mediated dilation in collateral‐dependent coronary arterioles.Support or Funding InformationNational Institutes of Health R01‐HL139903

Single cell RNA sequencing (scRNAseq) of severely atherosclerotic coronary artery from Ossabaw miniature swine with metabolic syndrome

IntroductionCoronary atherogenesis involves multiple signaling pathways and underlying gene expression. The atherogenic plasma milieu (excess lipoproteins, glucose, etc.) injures the endothelium, which is the initiating event of coronary plaque development. Subsequently, smooth muscle cells proliferate and migrate from the wall into the neointima, and blood cells and macrophages infiltrate the vessel wall and contribute to the growing plaque. Our goal was to characterize the gene expression in the heterogeneous cell population in this dynamic coronary artery pathology.MethodsWe performed single cell RNA sequencing (scRNAseq) on cells dispersed from the proximal 45 mm of the left anterior descending coronary artery of healthy pigs compared to separate plaque and wall cell dispersions from arteries of Ossabaw swine that had metabolic syndrome and were atherosclerotic for 23 months. Primary analysis scRNAseq data used t‐distributed stochastic neighbor embedding (T‐SNE) plots for an integrated analysis of the 3 cell preparations.ResultsMetabolic syndrome was confirmed by obesity, dyslipidemia, and hypertension. In vivo intravascular ultrasound (IVUS) of the entire artery revealed every stage of atherosclerosis from fatty streak to complex lesions having up to 70% occlusion with fibrofatty and calcified lesions. Cells (3,510) from healthy coronary artery expressed predominantly markers for endothelial (PECAM1), endocardial (CDH5, POSTN), and smooth muscle cells (ACTA2, TAGLN, CNN1, MYL9, CALD1, RGS5, MHY11). Overall, the healthy coronary artery cells were much more homogeneous than atherosclerotic plaque and wall cells. Wall cells (8,224) in atherosclerotic arteries expressed ~no (0.1%) endothelial, many smooth muscle, and fibroblast genes. Plaque cells (8,049) expressed ~no (0.1%) endothelial genes, robust smooth muscle marker genes, and a high abundance of early marker genes for chondrocytes, osteoblasts, monocytes, neutrophils, and macrophages.ConclusionProfound gene expression patterns were shown with scRNAseq in a clinically relevant model of coronary atherosclerosis. The striking heterogeneity of gene expression and marker genes for chondrocytes and osteoblasts in plaque cells indicate significant transdifferentiation and suggest further progression to severe coronary artery calcification.

Impact of hydrostatic pressure on fractional flow reserve: in vivo experimental study of anatomical height difference of coronary arteries

BackgroundAlthough pressure equalization of the sensor-tipped guidewire and systemic pressure is mandatory in measuring fractional flow reserve (FFR), pressure in the distal artery (Pd) with wire advancement can be influenced by hydrostatic pressure related to the height difference between the catheter tip and the distal pressure sensor. We therefore analyzed the impact of hydrostatic pressure on FFR in vivo by modification of the height difference. MethodsTo reveal the anatomical height difference in human coronary arteries, measurement was performed during computed tomography angiography (CTA) of five consecutive patients. Utilizing the healthy coronary arteries of female swine, height difference diversity was reproduced by body rotation and vertical inclination. FFR measurements were performed during maximum hyperemia with adenosine. The height difference was calculated fluoroscopically with a contrast medium–filled balloon for reference. ResultsIn human coronary CTA, height averages from the ostium in the left anterior descending artery (34.6 mm) were significantly higher than in the left circumflex (−15.5 mm, p = 0.008) and right coronary arteries (−2.3 mm, p = 0.008). In our swine model, reproduced height variation ranged from −7.2 cm to +6.5 cm. Mean FFR was significantly lower in positive sensor height and higher in negative sensor height compared to the reference height. Linear regression analyses revealed significant correlations between height difference and FFR, observed among all coronary arteries, as well as between the height difference and Pd–aortic pressure mismatch. Subtracting 0.622 mmHg/cm height difference from Pd could correct the expected hydrostatic pressure influence. ConclusionHydrostatic pressure variation resulting from sensor height influenced FFR values might affect interpretation during FFR assessment.

Stabilizing Peri-Stent Restenosis Using a Novel Therapeutic Carrier

Late in-stent restenosis remains a significant problem. Bare-metal stents were implanted into peripheral arteries in miniature swine, followed by direct intra-arterial infusion of nitric oxide-loaded echogenic liposomes (ELIPs) and anti-intercellular adhesion molecule-1 conjugated ELIPs loaded with pioglitazone exposed to an endovascular catheter with an ultrasonic core. Ultrasound-facilitated delivery of ELIP formulations into stented peripheral arteries attenuated neointimal growth. Local atheroma-targeted, ultrasound-triggered delivery of nitric oxide and pioglitazone, an anti-inflammatory peroxisome proliferator-activated receptor-γ agonist, into stented arteries has the potential to stabilize stent-induced neointimal growth and obviate the need for long-term antiplatelet therapy.

Distribution of pressure gradients along the left anterior descending artery in patients with angiographically normal arteries.

This study tested the hypothesis that there is no decline of coronary pressure from the proximal to the distal left anterior descending coronary artery (LAD) of humans and swine. In the daily clinical practice, the fractional flow reserve (FFR) in the LAD is frequently lower than that in the other arteries in the presence of a similar degree of stenosis. Twenty-six patients with angiographically normal LAD were prospectively enrolled. The coronary pressure ratio (mean distal/proximal coronary pressures at hyperemia) was measured at five different positions: 12, 10, 7, and 5 cm distal from the LAD ostium, and at the ostium of the LAD. The coronary pressure measurement was further investigated in a swine model without atherosclerosis. The coronary pressure ratio during maximum hyperemia gradually decreased in proportion to the distance from the ostium (average: 0.85 ± 0.06 at 12 cm distal to the ostium). This finding was confirmed in swine model. The degree of the coronary pressure decrease during maximum hyperemia was similar in patients with and without evidence of minor plaque on intravascular ultrasound, however it was strongly associated with the amount of myocardium mass in the territory of the LAD. Intracoronary pressure gradually decreases in proportion to the distance from the ostium in the LAD of humans and swine, regardless of the presence of minor atherosclerotic plaques. The degradation degree of the coronary pressure ratio during maximum hyperemia is enlarged in the presence of larger amount of myocardium mass in the territory of the LAD.

Reduction of radiation exposure to operating physician and assistant using a real-time auditory feedback dosimeter during femoral artery puncturing: a study on swine model

BackgroundReal-time dosimeters may create a relatively safer environment not only for the patient but also for the physician and the assistant as well. We propose the use of a real-time radiation measurement dosimeter having auditory feedback to reduce radiation exposure.MethodsRadiation dose rates were measured for 30 fluoroscopy-guided puncturing procedures of femoral arteries in swine. Fifteen puncturing procedures were performed with real-time radiation measurement dosimeter having auditory feedback and other 15 were performed without auditory feedback dosimeter by an interventional cardiologist with 10 years of experience.ResultsThe left body side of the operating physician (38%, p < 0.001) and assistant (25%, p < 0.001) was more exposed as compared to the right body side. Radiation dose rate to the left hand, left arm and left leg were reduced from 0.96 ± 0.10 to 0.79 ± 0.12 mSv/h (17% reduction, p < 0.001), from 0.11 ± 0.02 to 0.07 ± 0.01 mSv/h (36% reduction, p < 0.001) and from 0.22 ± 0.06 to 0.15 ± 0.02 mSv/h (31% reduction, p < 0.001) with the use of auditory feedback dosimeter, respectively. The mean fluoroscopic time was reduced from 4.8 ± 0.43 min to 4.2 ± 0.53 min (p < 0.001). The success rate of performing arterial puncturing was 100%.ConclusionsThe use of auditory feedback dosimeter resulted in reduction in effective dose. The sound beep alerted the physician from the danger of exposure, and this approach induced awareness and protective mindset to the operating physician and assistant.

High-density lipoprotein remodelled in hypercholesterolaemic blood induce epigenetically driven down-regulation of endothelial HIF-1α expression in a preclinical animal model.

AimsHigh-density lipoproteins (HDLs) are circulating micelles that transport proteins, lipids, and miRNAs. HDL-transported miRNAs (HDL-miRNAs) have lately received attention but their effects on vascular cells are not fully understood. Additionally, whether cardiovascular risk factors affect HDL-miRNAs levels and miRNA transfer to recipient cells remains equally poorly known. Here, we have investigated the changes induced by hypercholesterolaemia on HDL-miRNA levels and its effect on recipient endothelial cells (ECs).Methods and resultsPigs were kept on a high-fat diet (HC; n = 10) or a normocholesterolaemic chow (NC; n = 10) for 10 days reaching cholesterol levels of 321.0 (229.7–378.5) mg/dL and 74.0 (62.5–80.2) mg/dL, respectively. HDL particles were isolated, purified, and quantified. HDL-miRNA profiling (n = 149 miRNAs) of HC- and NC-HDLs was performed by multipanel qPCR. Cell cultures of porcine aortic ECs were used to determine whether HDL-miRNAs were delivered to ECs. Potential target genes modulated by miRNAs were identified by bioinformatics and candidate miRNAs were validated by molecular analysis. In vivo effects in the coronary arteries of normocholesterolaemic swine administered HC- or NC-HDLs were analysed. Among the HDL-miRNAs, four were found in different amounts in HC- and NC-HDL (P < 0.05). miR-126-5p and -3p and miR-30b-5p (2.7×, 1.7×, and 1.3×, respectively) were found in higher levels and miR-103a-3p and miR-let-7g-5p (−1.6×, −1.4×, respectively) in lower levels in HC-HDL. miR-126-5p and -3p were transferred from HC-HDL to EC (2.5×; P < 0.05), but not from NC-HDL, by a SRB1-mediated mechanism. Bioinformatics revealed that HIF1α was the miR-126 target gene with the highest predictive value, which was accordingly found to be markedly reduced in HC-HDL-treated ECs and in miR126 mimic transfected ECs. In vivo validation confirmed that HIF1α was diminished in the coronary endothelial layer of NC pigs administered HC-HDL vs. those administered NC-HDL (P < 0.05).ConclusionHypercholesterolaemia induces changes in the miRNA content of HDL enhancing miR126 and its delivery to ECs with the consequent down-regulation of its target gene HIF1α.

Modulation of Cathepsin L Expression in the Coronary Arteries of Atherosclerotic Swine

IntroductionNeointimal hyperplasia (NIH) and restenosis after percutaneous transluminal coronary angioplasty (PTCA) and intravascular stenting remain a problem on a long-term basis by causing endothelial denudation and damage to the intima and media. Vascular sterile inflammation has been attributed to the formation of NIH. Cathepsin L (CTSL), a lysosome protease, is associated with diet-induced atherogenesis. Vitamin D regulates the actions and regulatory effects of proteases and protease inhibitors in different cell types. Objectives of this study are to evaluate the modulatory effect of vitamin D on CTSL activity in post-PTCA coronary arteries of atherosclerotic swine. MethodsYucatan microswine were fed with high-cholesterol atherosclerotic diets. The swine were stratified to receive three diets: (1) vitamin D–deficient diet, (2) vitamin D–sufficient diet, and (3) vitamin D–supplement diet. After 6 mo, PTCA was performed in the left circumflex coronary artery (LCx). After 1 y, angiography and optical coherence tomography imaging were performed, and swine was euthanized. Coronary arteries were embedded in paraffin. Tissue sections were stained with hematoxylin and eosin. Expression of Ki67 and CTSL were evaluated by immunofluorescence. ResultsIncreased number of Ki67 + cells were observed in the postangioplasty LCx in vitamin D–deficient compared with vitamin D–sufficient or vitamin D–supplemented swine. Notably, the expression of CTSL was significantly increased in postangioplasty LCx of vitamin D–deficient swine compared with the vitamin D–sufficient or vitamin D–supplemented animal groups. ConclusionsIncreased expression of CTSL correlates with the formation of NIH in the PTCA-injured coronary arteries. However, in the presence of sufficient or supplemented levels of vitamin D in the blood, CTSL expression was significantly reduced.

Fabrication of an expandable keratin sponge for improved hemostasis in a penetrating trauma

Effective hemostasis improvements for penetrating traumas remain a research priority for civilian and noncivilian applications. Herein, we fabricated an expandable keratin sponge (EKS) for the hemostatic treatment of a penetrating trauma based on the excellent hemostatic ability of keratin and the expandable property of polyacrylamide (PAM). EKSs with semi-interpenetrating networks were fabricated by radical polymerization of keratin and PAM, and the EKS showed rapid expansion upon blood absorption. This sponge exhibited effective hemostasis on a rat penetrating liver hemorrhage, and the expansion of the EKS was dependent on the bleeding volume. In addition, the results of a shear wave elastography analysis showed that the elasticity of the liver tissue increased from 12.5 kPa to 21.2 kPa after the penetrating liver trauma treated by the EKS, and the mechanical strength of the liver tissue was maintained after 1 h of the EKS application. Further in vivo tests indicated the effectiveness of the EKS for hemostasis in a swine femoral artery transection hemorrhage model. This EKS is promising for hemostatic applications.