Fault Diagnosis for High-Speed Train Axle-Box Bearing Using Simplified Shallow Information Fusion Convolutional Neural Network.

Axle-box bearings are one of the most critical mechanical components of the high-speed train. Vibration signals collected from axle-box bearings are usually nonlinear and nonstationary, caused by the complicated operating conditions. Due to the high reliability and real-time requirement of axle-box bearing fault diagnosis for high-speed trains, the accuracy and efficiency of the bearing fault diagnosis method based on deep learning needs to be enhanced. To identify the axle-box bearing fault accurately and quickly, a novel approach is proposed in this paper using a simplified shallow information fusion-convolutional neural network (SSIF-CNN). Firstly, the time domain and frequency domain features were extracted from the training samples and testing samples before been inputted into the SSIF-CNN model. Secondly, the feature maps obtained from each hidden layer were transformed into a corresponding feature sequence by the global convolution operation. Finally, those feature sequences obtained from different layers were concatenated into one-dimensional as the fully connected layer to achieve the fault identification task. The experimental results showed that the SSIF-CNN effectively compressed the training time and improved the fault diagnosis accuracy compared with a general CNN.

Spatial variation and health risk assessment of fluoride in drinking water in the Chongqing urban areas, China.

Fluoride is an essential trace element for humans, and its deficiency or excess in the environment could lead to disease. To investigate the spatial distribution and health risk assessment of fluoride (F-) in drinking water, 302 tap water samples from Chongqing urban areas, China, were collected to analyze F- using an ion chromatograph. The results showed that (1) F- concentration in drinking water ranged from 0.100 to 0.503 mg/L, with an average of 0.238 ± 0.045 mg/L. (2) The spatial autocorrelation analysis showed that high-low clusters were mostly located in Dadukou District and Beibei District, while low-low clusters were mainly in southern Banan District. (3) The fluoride average daily doses of children, teens and adults were 0.030, 0.029 and 0.031 mg/(kg day). (4) Hazard quotients of excessive fluoride (HQe) of children, teens and adults were 0.51 ± 09, 0.49 ± 0.09 and 0.52 ± 0.10, respectively (inferior to 1.00), whereas hazard quotients of inadequate fluoride (HQi) of those groups were 1.21 ± 0.26, 1.23 ± 0.26 and 1.15 ± 0.25, respectively (superior to 1.00). Therefore, average daily fluoride intake of residents with drinking water was inadequate. This could pose dental caries and osteoporosis threats for residents from Chongqing urban areas.

Intracoronary and retrograde coronary venous myocardial delivery of adipose-derived stem cells in swine infarction lead to transient myocardial trapping with predominant pulmonary redistribution.

OBJECTIVES: To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous (RCV) or arterial delivery. BACKGROUND: Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium. METHODS: In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary (IC) delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either IC or RCV infusion of 10(7) (111)Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hr after cell delivery. RESULTS: IC delivery of porcine ASCs to normal myocardium was well tolerated up to a cumulative dose of 14 × 10(6) cells (approximately 0.5 × 10(6) cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50 × 10(6) ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, whereas at 10 × 10(6) ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hr with IC delivery compared with RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, P = 0.037) but this initial difference was not apparent at 24 hr (22.6 ± 5.5% vs. 18.7 ± 8.6%; P = 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hr postdelivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route. CONCLUSIONS: Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. IC arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise.

Endothelium-Mimicking Nanomatrix Coating to Enhance Endothelialization after Left Atrial Appendage Closure Device Implantation.

Blood clots (90%) originate from the left atrial appendage (LAA) in non-valvular atrial fibrillation patients and are a major cause of embolic stroke. Long-term anticoagulation therapy has been used to prevent thrombus formation, but its use is limited in patients at a high risk for bleeding complications. Thus, left atrial appendage closure (LAAC) devices for LAA occlusion are well-established as an alternative to the anticoagulation therapy. However, the anticoagulation therapy is still required for at least 45 days post-implantation to bridge the time until complete LAA occlusion by neoendocardium coverage of the device. In this study, we applied an endothelium-mimicking nanomatrix to the LAAC device membrane for delivery of nitric oxide (NO) to enhance endothelialization, with the goal of possibly being able to reduce the duration of the anticoagulation therapy. The nanomatrix was uniformly coated on the LAAC device membranes and provided sustained release of NO for up to 1 month in vitro. In addition, the nanomatrix coating promoted endothelial cell proliferation and reduced platelet adhesion compared to the uncoated device membranes in vitro. The nanomatrix-coated and uncoated LAAC devices were then deployed in a canine LAA model for 22 days as a pilot study. All LAAC devices were not completely covered by neoendocardium 22 days post-implantation. However, histology image analysis showed that the nanomatrix-coated LAAC device had thicker neoendocardium coverage compared to the uncoated device. Therefore, our in vitro and in vivo results indicate that the nanomatrix coating has the potential to enhance endothelialization on the LAAC device membrane, which could improve patient outcomes by shortening the need for extended anticoagulation treatment.

The pharmacokinetic profiles of dexamethasone and methylprednisolone concentration in perilymph and plasma following systemic and local administration.

CONCLUSION: Both methylprednisolone (MTH) and dexamethasone (DEX) could successfully and effectively penetrate the round window membrane (RWM) into perilymph. RWM topical application and otocyst infusion with MTH and DEX result in high perilymph drug concentrations and low plasma levels. An intratympanic administration schedule for DEX or MTH could be carried out twice daily. OBJECTIVE: To explore the pharmacokinetics of DEX and MTH in the inner ear fluids and plasma following systemic and local administration. MATERIALS AND METHODS: Three routes of administration of steroids were used in guinea pigs: intracardial injection, otocyst infusion and RWM topical application by granule gelfoam soaked with steroids. Samples of blood or perilymph of the scala tympani were collected at 1-6 h after administration. High-performance liquid chromatography was used to assay concentrations of steroids. RESULTS: Both the topical application and infusion administration resulted in a significantly higher concentration of steroids in perilymph than intracardial injection. The level of steroids in the perilymph reached a peak at 1-2 h after dosing, and this was maintained at a relatively high level for several hours. The intracardial injection with steroids yielded very low perilymph levels at all sampling times after administration.

Acute myocardial infarction in swine rapidly and selectively releases highly proliferative endothelial colony forming cells (ECFCs) into circulation.

We have recently identified endothelial colony forming cells (ECFCs) in human blood and blood vessels, and ECFC are elevated in patients with coronary artery disease. Because pigs are a favored model for studying myocardial ischemia, we questioned whether ECFCs also exist in swine and whether myocardial ischemia would alter the number of ECFC in circulation. ECFCs were present in circulating blood and aortic endothelium of healthy pigs. In pigs with an acute myocardial infarction (AMI) (n = 9), the number of circulating ECFC was markedly increased compared to sham control pigs (15 +/- 6 vs. 1 +/- 1 colonies/100 cc blood, p < 0.05). Moreover, the percentage of circulating high proliferative potential ECFCs (HPP-ECFCs) was significantly increased following AMI induction compared to sham control (38.4 +/- 5.8% vs. 0.4 +/- 0.4%, p < 0.05) and to baseline (38.4 +/- 5.8% vs. 2.4 +/- 2.4%, p < 0.05) blood samples. This is the first study to report that ECFCs are present in blood and aorta in healthy pigs and that the number and distribution of circulating ECFCs is altered following AMI. Because circulating ECFC are also altered in human subjects with severe coronary artery disease, the pig model of AMI may be an excellent preclinical model to test the role of ECFC in the pathophysiology of AMI.

Intrahepatic HBV DNA as a predictor of antivirus treatment efficacy in HBeAg-positive chronic hepatitis B patients.

AIM: To evaluate the effect of antiviral agents on intrahepatic HBV DNA in HBeAg-positive chronic hepatitis B patients. METHODS: Seventy-one patients received treatment with lamivudine, interferon alpha (IFN-alpha 2b) or sequential therapy with lamivudine-IFN-alpha 2b for 48 wk. All subjects were followed up for 24 wk. Serum and intrahepatic HBV DNA were measured quantitatively by PCR. HBV genotypes were analyzed by PCR-RFLP. RESULTS: At the end of treatment, the intrahepatic HBV DNA level in 71 patients decreased from a mean of (6.1 +/- 1.0) log10 to (4.9 +/- 1.4) log10. Further, a larger decrease was seen in the intrahepatic HBV DNA level in patients with HBeAg seroconversion. Intrahepatic HBV DNA level (before and after treatment) was not significantly affected by the patients' HBV genotype, or by the probability of virological flare after treatment. CONCLUSION: Intrahepatic HBV DNA can be effectively lowered by antiviral agents and is a significant marker for monitoring antivirus treatment. Low intrahepatic HBV DNA level may achieve better efficacy of antivirus treatment.

Current State of Bioabsorbable Polymer-Coated Drug-Eluting Stents.

Drug-eluting stents (DES) have been shown to significantly reduce clinical and angiographic restenosis compared to bare metal stents (BMS). The polymer coatings on DES elute antiproliferative drugs to inhibit intimal proliferation and prevent restenosis after stent implantation. Permanent polymers which do not degrade in vivo may increase the likelihood of stent-related delayed arterial healing or polymer hypersensitivity. In turn, these limitations may contribute to an increased risk of late clinical events. Intuitively, a polymer which degrades after completion of drug release, leaving an inert metal scaffold in place, may improve arterial healing by removing a chronic source of inflammation, neoatherosclerosis, and/or late thrombosis. In this way, a biodegradable polymer may reduce late ischemic events. Additionally, improved healing after stent implantation could reduce the requirement for long-term dual antiplatelet therapy and the associated risk of bleeding and cost. This review will focus on bioabsorbable polymer-coated DES currently being evaluated in clinical trials.

Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials.

BACKGROUND: Several clinical studies are evaluating the therapeutic potential of delivery of various progenitor cells for treatment of injured hearts. However, the actual fate of delivered cells has not been thoroughly assessed for any cell type. We evaluated the short-term fate of peripheral blood mononuclear cells (PBMNCs) after intramyocardial (IM), intracoronary (IC), and interstitial retrograde coronary venous (IRV) delivery in an ischemic swine model. METHODS AND RESULTS: Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 10(7) 111indium-oxine-labeled human PBMNCs were delivered by IC (n=5), IM (n=6), or IRV (n=5) injection. The distribution of injected cells was assessed by gamma-emission counting of harvested organs. For each delivery method, a significant fraction of delivered cells exited the heart into the pulmonary circulation, with 26+/-3% (IM), 47+/-1% (IC), and 43+/-3% (IRV) of cells found localized in the lungs. Within the myocardium, significantly more cells were retained after IM injection (11+/-3%) compared with IC (2.6+/-0.3%) (P<0.05) delivery. IRV delivery efficiency (3.2+/-1%) trended lower than IM infusion for PBMNCs, but this difference did not reach significance. The IM technique displayed the greatest variability in delivery efficiency by comparison with the other techniques. CONCLUSIONS: The majority of delivered cells is not retained in the heart for each delivery modality. The clinical implications of these findings are potentially significant, because cells with proangiogenic or other therapeutic effects could conceivably have effects in other organs to which they are not primarily targeted but to which they are distributed. Also, we found that although IM injection was more efficient, it was less consistent in the delivery of PBMNCs compared with IC and IRV techniques.

Fluorocopolymer-coated nitinol self-expanding paclitaxel-eluting stent: pharmacokinetics and vascular biology responses in a porcine iliofemoral model.

AIMS: Our aim was to evaluate arterial responses to paclitaxel and a novel fluorocopolymer-coated nitinol low-dose paclitaxel-eluting stent (FP-PES). METHODS AND RESULTS: Human smooth muscle cell (SMC) migration was assessed after exposure to paclitaxel in vitro. For pharmacokinetics and vascular response, FP-PES or bare metal stents (BMS) were implanted in porcine iliofemoral arteries. Paclitaxel significantly inhibited human coronary and femoral artery SMC migration at doses as low as 1 pM. Inhibition was significantly greater for femoral compared with coronary artery SMCs from 1 pM to 1 µM. Pharmacokinetics showed consistent paclitaxel release from FP-PES over the study duration. The peak arterial wall paclitaxel level was 3.7 ng/mg at 10 days, with levels decreasing to 50% of peak at 60 days and 10% at 180 days. Paclitaxel was not detected in blood or remote organs. Arteriogram and histomorphometry analyses showed FP-PES significantly inhibits neointimal proliferation versus BMS at 30 and 90 days. Re-endothelialisation scores were not different between groups. CONCLUSIONS: Paclitaxel affected femoral artery SMC migration at lower concentrations and to a greater degree than it did coronary artery SMCs. The novel FP-PES used in this preclinical study demonstrated a vascular healing response similar to BMS, while significantly inhibiting neointimal formation up to 90 days.

Augmentation of intrapericardial nitric oxide level by a prolonged-release nitric oxide donor reduces luminal narrowing after porcine coronary angioplasty.

BACKGROUND: Nitric oxide (NO) is a potent vasodilator and antiplatelet agent that suppresses vascular smooth muscle cell proliferation. Hypothesizing that generating NO in the pericardial space would reduce luminal narrowing after coronary angioplasty without affecting systemic hemodynamics, we have determined the effect of a novel NO donor on vascular healing after balloon overstretch. METHODS AND RESULTS: Diazeniumdiolated bovine serum albumin (D-BSA; molecular weight 74 kDa, half-life for NO release 20 days) was radioiodinated and found by intravital gamma-imaging to have a longer residence time in pig pericardium than a low-molecular-weight (0.5 kDa) analogue (22 versus 4.6 hours, respectively). Intrapericardial injection of D-BSA immediately before 30% overstretch of normal left anterior descending and left circumflex coronary arteries dose dependently reduced the intimal/medial area ratio by up to 50% relative to controls treated with underivatized albumin when measured 2 weeks after intervention. Positive remodeling was also noted, which increased luminal area relative to control. CONCLUSIONS: Perivascular exposure of coronary arteries to NO via intrapericardial D-BSA administration reduced flow-restricting lesion development after angioplasty in pigs without causing significant systemic effects. The data suggest that intrapericardial delivery of NO donors for which NO release rates and pericardial residence times are matched and optimized might be a beneficial adjunct to coronary angioplasty.

Inhibitory effects of metformin at low concentration on epithelial-mesenchymal transition of CD44(+)CD117(+) ovarian cancer stem cells.

BACKGROUND: Although metformin, a first-line drug for treating diabetes, may play an important role in inhibition of epithelial ovarian cancer cell growth and cancer stem cells (CSCs), metformin at low dose showed less effect on the proliferation of ovarian cancer cells. In this study, we evaluated the effect of metformin at low dose on ovarian CSCs in order to understand the molecular mechanisms underlying. METHODS: The inhibitory effects of metformin at los dose on proliferation and population of ovarian cancer cells including SKOV3 and A2780 were assessed by cell proliferation assay and flow cytometry. Quantitative real-time PCR assay on expression of Bcl-2, Survivin and Bax was performed to determine the effect of metformin at low dose on epithelial-mesenchymal transition (EMT) of cancer cells and CSCs. Tumor sphere formation assay was also performed to evaluate the effect of metformin on spheres forming ability of CSCs. The therapeutic efficacy and the anti-CSC effects of metformin at low dose were investigated by using both SKOV3 cells and primary tumor xenografts. In addition, the CSC frequency and EMT in tumor xenograft models were also assessed by flow cytometry and quantitative real-time PCR. RESULTS: Metformin at low dose did not affect the proliferation of ovarian cancer cells. However, it inhibited population of CD44(+)CD117(+) selectively, neither CD133(+) nor ALDH(+) cells. It suppressed expression of snail2, twist and vimentin significantly in cancer cells and CD44(+)CD117(+) CSCs in vitro. Low dose of metformin reduced survivin expression in CSCs. Low concentrations of metformin inhibited the secondary and the tertiary tumor sphere formation, decreased SKOV3 and primary ovarian tumor xenograft growth, enhanced the anticancer effect of cisplatin, and lowered the proportion of CD44(+)CD117(+) CSCs in the xenograft tissue. Metformin was also associated with a reduction of snail2, twist, and vimentin in CD44(+)CD117(+) ovarian CSCs in vivo. CONCLUSIONS: Our results implicate that metformin at low dose inhibits selectively CD44(+)CD117(+) ovarian CSCs through inhibition of EMT and potentiates the effect of cisplatin.

A comparison of drug eluting stent biocompatibility between third generation NOBORI biolimus A9-eluting stent and second generation XIENCE V everolimus-eluting stent in a porcine coronary artery model.

BACKGROUND AND PURPOSE: NOBORI biolimus A9-eluting stent (BES) is the third generation drug eluting stent (DES) with only abluminal biodegradable polymer. Recent clinical trials have indicated that the BES is non-inferior to the XIENCE V everolimus-eluting stent (EES). Meanwhile, potential superiority of biodegradable polymer BES over current generation DES has not been addressed. The aim of this preclinical study was to assess and compare the biocompatibility of both BES and EES in porcine coronary arteries. METHODS AND MATERIALS: BES with length of 24-mm (n=9) and EES with length of 23-mm (n=9) were both implanted in porcine coronary arteries. At 28 days endothelium-dependent vasomotion was assessed by acetylcholine (Ach) and subsequently measurements of endothelial superoxide production, histological evaluations and microarray gene analyses were performed. RESULTS: Angiographic and histological in-stent stenoses were significantly suppressed in BES compared with EES. Histopathological assessment showed lower inflammatory score as well as fibrin and injury scores in BES as compared with EES. On the contrary, paradoxical vasoconstriction to Ach was frequently observed in EES-treated vessels compared with BES-treated vessels. Additionally, gene expressions of inflammatory cytokines and chemokines were upregulated in vessels treated with EES compared with BES in microarray pathway specific analyses. CONCLUSIONS: Implantation of BES revealed less inflammation and foreign-body immunoreaction than EES, suggesting more enhanced biocompatibility of BES compared with EES at 28 days in porcine coronary arteries.

Left Atrial Appendage Closure -The WATCHMAN Device.

Atrial fibrillation (AF) is one of the most common arrhythmias seen in clinical cardiology practice. Patients with non-valvular AF have an approximately 5-fold increase in the risk of stroke, with an exponential increase with advancing age. Cardioembolic strokes carry a high mortality risk. Although the potential of warfarin to reduce systemic embolization in AF patients is well established, its use is difficult due to narrow therapeutic windows and additional complications (e.g. increased risk of bleeding), especially for aging patients. Therefore, alternative means of treatment to reduce stroke risk in these patients are needed. The left atrial appendage is the major source of thrombus formation in patients with non-valvular AF. The WATCHMAN device (Boston Scientific, MA) is a percutaneous left atrial appendage closure device which has been tested prospectively in multiple randomized trials. It offers a new stroke risk reduction option for high-risk patients with non-valvular atrial fibrillation who are seeking an alternative to long-term warfarin therapy. Based on the robust WATCHMAN clinical program which consists of numerous studies, with more than 2,400 patients and nearly 6,000 patient-years of follow-up, the WATCHMAN LAAC Device is approved by FDA. In this article we reviewed the preclinical studies and clinical trials, as well as the next generation of the device.

A novel percutaneous technique for accessing the normal pericardium: a single-center successful experience of 53 porcine procedures.

Recently, the pericardial space has been under consideration as an ideal site for prevention and treatment of coronary artery and heart disease. Historically, safe percutaneous entry has not been possible to sample or remove pericardial fluids for diagnostic purposes or to employ therapeutic agents in the absence of a sizable pericardial effusion. A non-surgical percutaneous approach to permit rapid access to the normal or minimally effused pericardial space holds high potential for considerable diagnostic and therapeutic utility. This study examines the utility of the PerDUCER pericardial access device, a simplistic approach to permit percutaneous access to the normal, minimal or diseased pericardial space, in a large series of animals (swine). The PerDUCER , inserted through the introducer sheath in a sub-xiphoid position, allowed capture and delivery of the intrapericardial guidewire into the pericardial space in all animals. The procedure was well tolerated by all animals and exhibited no signs of significant adverse hemodynamic effects. Twelve animals were sacrificed immediately after the experiment, while 41 animals were sacrificed 28 days after the procedure. Histologic examination showed no occurrence of epicardial vessel or myocardial damage. In addition, no late complications were found related to pericardial access with the PerDUCER . This initial experiment demonstrates that the PerDUCER provides an efficient, safe and effective technique to gain pericardial access in the normal or minimal pericardial space to obtain diagnostic sampling of the pericardial fluids and renders local intrapericardial delivery of therapeutic agents a possibility.

Intrapericardial ethanol delivery inhibits neointimal proliferation after porcine coronary overstretch.

BACKGROUND: Previous work has shown that ethanol dampens cell growth signals and inhibits smooth muscle proliferation in a restenosis model. Catheter-based approaches to intrapericardial (IPC) delivery of therapeutic agents have been recently demonstrated to be feasible. This study tested the effect of IPC instillation of ethanol on the injury response of overstretched porcine coronary arteries. METHODS: Ethanol, 30%, (E, 10 mL, n = 6) or saline, 0.9%, (C, 10 mL, n = 6) was administered IPC after overstretch injury of porcine coronary arteries. Animals were sacrificed 28 days after balloon dilation. RESULTS: The neointimal and adventitial area were significantly reduced in the E group (0.36 +/- 0.05 mm2; 1.68 +/- 0.09 mm2) as compared to the C group (0.61 +/- 0.05 mm2; 2.61 +/- 0.14 mm2; p < 0.001). The maximal intimal and adventitial thicknesses of the treated vessels were also significantly smaller than those of untreated vessels (0.44 +/- 0.02, 0.38 +/- 0.08 mm vs 0.57 +/- 0.03, 0.54 +/- 0.03 mm, respectively; p < 0.005). The calculated luminal stenosis decreased in the treated group, 16.1%, versus the control group, 25.3%. CONCLUSION: Perivascular administration of a single-dose of ethanol significantly reduce neointimal proliferation in the porcine balloon-overstretch model. This data suggests that intrapericardial delivery of therapeutic agents may be useful and feasible in the coronary angioplasty setting for prevention of restenosis.

Development of a novel adenosine-eluting guidewire (Adenowire) for coronary vasodilation during percutaneous coronary intervention.

AIMS: Microvascular obstruction (MVO) and "no-reflow phenomenon" (NRP) remain barriers to optimal tissue perfusion after percutaneous coronary intervention (PCI). The purpose of this study was to develop, characterise, and test an adenosine-eluting guidewire (Adenowire) for coronary vasodilation. METHODS AND RESULTS: Utilising polyurethane chemistry, we developed a non-toxic pentameric form of adenosine (PA) that can be coated onto guidewires (Adenowire) and that allows continuous elution of adenosine into the distal vascular bed during PCI. We characterised PA with Fourier transform infrared spectroscopy, NMR and MALDI time-of-flight mass spectrometry, established its stability by calorimetry, and confirmed its safety by extensive toxicological testing. Adenowires reliably released adenosine in vitro over 60 minutes. In pigs, insertion of an Adenowire into the left circumflex or left anterior descending coronary artery resulted in immediate and sustained (40 minutes) vasodilation. Electron microscopy demonstrated smooth thin coating of the terminal portion of guidewires and showed lack of fibrin or platelet adhesion to the Adenowire after in vivo use. CONCLUSIONS: Since guidewires are the first devices to cross a culprit lesion, Adenowires would prophylactically medicate vascular beds with adenosine at the target site without the need for additional manipulations by the interventionalist.

Impact of Watchman and Amplatzer devices on left atrial appendage adjacent structures and healing response in a canine model.

OBJECTIVES: This study was designed for conducting a comparative evaluation of the healing response after Watchman (WM) (Boston Scientific, Plymouth, Minnesota) and Amplatzer Cardiac Plug (ACP) (St. Jude Medical, Minneapolis, Minnesota) in a canine left atrial appendage (LAA) model. BACKGROUND: There is no direct comparison of the WM and ACP device in pre-clinical or clinical settings. METHODS: The LAA from canine (n = 6) and human (n = 19) hearts were compared to determine the feasibility of the canine model and its relevance to clinical applications. Subsequently, implantation of WM and ACP in the canine LAA was performed (n = 3 per device) to evaluate the device conformation to the LA anatomy as well as the healing response at 28 days. RESULTS: The LAA is a variable tubular structure in both canine and human hearts. Gross examination showed that the WM was properly seated inside the LAA ostium, in comparison to the ACP where the disk was outside of the LAA orifice and extended to the edge of the left superior pulmonary vein and mitral valve. At 28 days, complete neo-endocardial coverage of the WM was observed; however, the ACP showed an incomplete covering on the disk surface especially at the lower edge and end-screw hub regions. CONCLUSIONS: There are differences in conformation of LAA surrounding structures with variable healing response between WM and ACP after LAA closure in the canine model. WM does not obstruct or impact the LAA adjacent structures, resulting in a favorable surface recovery. In comparison, the disk of ACP could potentially jeopardize LAA neighboring structures and leads to delayed healing.

Optical coherence tomography and histopathological assessment of delayed arterial healing after drug-eluting stent implant in a pig coronary model.

BACKGROUND: Delayed healing, such as persistent inflammation and fibrin deposition, and vascular dysfunction after drug-eluting stent has been reported. Histological validation of coronary optical coherence tomography (OCT) morphology has not yet been done. METHODS: Sirolimus eluting stents (SES, n=8) and bare metal stents (BMS n=8) were implanted in pig coronary arteries. One month after implantation, an acetylcholine challenge test and OCT were performed. The OCT texture pattern of the neointima was classified into one of the three categories; Layered type, Homo type, and Hetero type. Hearts were harvested for histopathological scoring of inflammation and intramural thrombus. RESULTS: Inflammation and intramural thrombus scores were higher in the Hetero type than in the Layered type and Homo type. OCT intensity of the Homo type was higher than that of the Layered type and Hetero type. Most SES were of the Hetero type. Conversely, most BMS were of the Homo type. SES exhibited higher inflammation and intramural thrombus than BMS (1.72 ± 0.89 vs 1.00 ± 0.00, P=0.0003, 2.39 ± 0.70 vs 0.92 ± 0.28, P<0.001 respectively). After acetylcholine injection, the diameter change was 4.31 ± 4.80% for SES versus -3.68 ± 6.81% for BMS (P=0.024). CONCLUSIONS: The Hetero type texture pattern in OCT images was associated with histological inflammation and intramural thrombus predominantly found in SES, and is related to endothelial dysfunction.