High-resolution computed tomographic (HRCT) image series from 413 canid and 18 felid skulls.

Computed tomography (CT) is a non-invasive, three-dimensional imaging tool used in medical imaging, forensic science, industry and engineering, anthropology, and archaeology. The current study used high-resolution medical CT scanning of 431 animal skulls, including 399 dog skulls from 152 breeds, 14 cat skulls from 9 breeds, 14 skulls from 8 wild canid species (gray wolf, golden jackal, coyote, maned wolf, bush dog, red fox, Fennec fox, bat-eared fox), and 4 skulls from 4 wild felid species (wildcat, leopard, serval, caracal). This comprehensive and unique collection of CT image series of skulls can provide a solid foundation not only for comparative anatomical and evolutionary studies but also for the advancement of veterinary education, virtual surgery planning, and the facilitation of training in sophisticated machine learning methodologies.

CT reconstruction based 3D model of the digital cushion's blood supply in the hind foot of an African savanna elephant (Loxodonta africana).

Introduction: Foot health is crucial for elephants, as pathological lesions of the feet are a leading cause of euthanasia in captive elephants, which are endangered species. Proper treatment of the feet, particularly in conditions affecting the digits and the digital cushion, requires a thorough understanding of the underlying anatomy. However, only limited literature exists due to the small population and the epidemiological foot diseases which often precludes many deceased elephants from scientific study. The aim of this study was to provide a detailed anatomical description of the blood supply to the African elephant's hindfoot. Methods: The healthy right hindlimb of a 19-year-old deceased female African savanna elephant was examined using computed tomography. Following a native sequence, 48 mL of barium-based contrast agent was injected into the caudal and cranial tibial arteries, and a subsequent scan was performed. The images were processed with 3D Slicer software. Results: The medial and lateral plantar arteries run in a symmetrical pattern. They each have a dorsal and a plantar branch, which reach the plantar skin before turning toward the axial plane of the sole to reach the digital cushion from the proximal direction. An accurate 3D model of the arteries and the bones of the foot, a set of labeled images and an animation of the blood supply have been created for ease of understanding. Discussion: In contrast to domestic ungulates, the digital cushion of the hindlimb is supplied differently from that of the forelimb. The lack of large vessels in its deeper layers indicates a slow regeneration time. This novel anatomical information may be useful in the planning of surgical interventions and in emergency medical procedures.

Rainbow trout (Oncorhynchus mykiss, Walbaum 1792) adenocarcinoma investigation with various diagnostic imaging techniques.

Diagnostic imaging techniques provide a new aspect of the ante-mortem and post-mortem diagnostics in fish medicine. Ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) can provide more information about the internal organs and pathognomic lesions. The authors used diagnostic imaging techniques to evaluate and describe the neoplastic malformation in a 3-year-old female rainbow trout (Oncorhynchus mykiss). The fish was examined with Siemens Somatom Definition AS + CT scanner and Siemens Biograph mMR scanner. The animal was lethargic and showed anorectic signs and muscular dystrophy. During the post-mortem investigation, histopathology and immunohistochemistry were also performed allowing us to identify the neoplasms. The results showed a large soft tissue mass in the first mid-intestine segment, which proved to be an adenocarcinoma. This subsequently led to digestion problems and absorption disorders. Immunohistochemically, neoplastic cells of carcinoma revealed E-cadherin and pancytokeratin positivity. This is the first study to report the use of MRI and CT for studying gastrointestinal adenocarcinoma in rainbow trout.

CT based 3D reconstruction of the forefoot's blood supply in a white rhinoceros.

BACKGROUND: The white rhinoceros (Ceratotherium simum) is close to extinction, listed as "Near Threatened", with a decreasing population on the Red List of Threatened Species of the International Union for Conservation of Nature. In at least 50% of the specimens in captivity, podiatric diseases, such as osteitis, osteomyelitis, chip fractures, enthesophytes, fractures and osteoarthritis were found during necropsy. These osteal deformations cause further pathogenic alterations in the soft tissues, particularly in the digital cushion. The literature provides good description of the skeleton of the rhino's limbs, but similar for the vascular system is non-existent. In order to recognize the symptoms in an early state and for a successful surgical treatment, precise knowledge of the vascular anatomy is essential. The purpose of our study was to provide detailed anatomical description of the blood supply of the digits and that of the digital cushion. RESULTS: The blood supply of the distal foot, digits and digital cushions were perfectly visible on the reconstructed and coloured 3D models. The deep palmar arch provided not only the blood supply to the digits but had a palmaro-distal running branch which developed a trifurcation proximal to the proximal sesamoid bones of the third digit. Two of its branches participated in the blood supply of the digits' proximal palmar surface, while the major branch supplied the digital cushion from proximal direction. CONCLUSIONS: Our findings show a unique blood supply: the main vessels of the digital cushion stem both directly from the deep palmar arch and from the digits' own arteries. The detailed description of vessels may be useful in planning surgery of the region and also in cases where the veins of the ear are not accessible.

3D Reconstruction of the Blood Supply in an Elephant's Forefoot Using Fused CT and MRI Sequences.

Being the largest still-living terrestrial mammal on earth, an elephant's feet play an important role in its health status. The musculoskeletal structures in the forefoot are well described in the literature, but information about vascularization is limited. The novel aim of this work is to provide anatomical guidance to structures found in the forefoot, focusing on the arterial system. Initially, native CT and MRI sequences were taken of the left forefoot of a deceased 6-year-old female Asian elephant; the foot was then filled with an iodine-containing contrast medium through the a. mediana and the CT scans were repeated in the same position. The images obtained were processed with 3D Slicer software for the 3D reconstruction of the bones and arteries. The results clearly showed the palmar blood supply of the forefoot. A so far undescribed vessel was revealed, stemming from the a. metacarpea, supplying the first digit and the digital cushion. The course of the deep palmar arch's terminal section was also established. This paper provides the first description of the exact disposition of the arteries in the palmar aspect of an elephant's forefoot and may be used in planning surgeries in clinically affected animals.

Vascular supply of the metacarpophalangeal joint.

Objective: To describe in detail the arterial vasculature of metacarpophalangeal joints 2-5 on cadaver specimens and to compare it to ultrasound imaging of healthy subjects. Methods: Eighteen hands of donated human cadavers were arterially injected and investigated with either corrosion casting or cryosectioning. Each layer of cryosectioned specimens was photographed in high-resolution. Images were then segmented for arterial vessels of the metacarpophalangeal (MCP) joints 2-5. The arterial pattern of the joints was reconstructed from the segmented images and from the corrosion cast specimens. Both hands of ten adult healthy volunteers were scanned focusing on the vasculature of the same joints with high-end ultrasound imaging, including color Doppler. Measurements were made on both cryosectioned arteries and Doppler images. Results: The arterial supply of MCP joints 2-5 divides into a metacarpal and a phalangeal territory, respectively. The metacarpal half receives arteries from the palmar metacarpal arteries or proper palmar digital arteries, while the phalangeal half is supplied by both proper and common palmar digital arteries. Comparing anatomical and ultrasonographic results, we determined the exact anatomic location of normal vessels using Doppler images acquired of healthy joints. All, except three branches, were found with less than 50% frequency using ultrasound. Doppler signals were identified significantly more frequently in MCP joints 2-3 than on 4-5 (p < 0.0001). Similarly, Doppler signals differed in the number of detectable small, intraarticular vessels (p < 0.009), but not that of the large extraarticular ones (p < 0.1373). When comparing measurements acquired by ultrasound and on cadaver vessels, measurements using the former technique were found to be larger in all joints (p < 0.0001). Conclusion: Using morphological and ultrasonographic techniques, our study provides a high-resolution anatomical maps and an essential reference data set on the entire arterial vasculature of healthy human MCP 2-5 joints. We found that Doppler signal could be detected in less than 50% of the vessels of healthy volunteers except three locations. Intraarticular branches were detected with ultrasound imaging significantly more frequently on healthy MCP 2-3 joints, which should be taken into account when inflammatory and normal Doppler signals are evaluated. Our study also provides reference data for future, higher-resolution imaging techniques.

Three-dimensional structure of the basal lamella of the middle turbinate.

The middle turbinate's basal lamella (3BL) is a variable landmark which needs to be understood in endoscopic transnasal skull base surgery. It comprises an anterior frontal and a posterior horizontal part and appears in its simplest depiction to be "L"-shaped, when viewed laterally. In this study we analyzed its 3D morphology and variations focusing on a precise and systematic description of the anatomy. CBCTs of 25 adults, 19 cadavers and 6 skulls (total: 100 sides) were investigated with the 3DSlicer software, creating 3D models of the 3BL. We introduced a novel geometrical classification of the 3BL's shape, based on segments. We analyzed their parameters and relationship to neighboring structures. When viewed laterally, there was no consistent "L"-shaped appearance of the 3BL, as it is frequently quoted. A classification of 9 segment types was used to describe the 3BL. The 3BLs had in average of 2.95 ± 0.70 segments (median: 3), the most frequent was the horizontal plate (23.05% of all segments), next a concave/convex plate (22.71%), then a sigma plate (22.37%). Further types were rare. We identified a horizontal plate in 68% of all lateral views whilst 32% of the 3BLs were vertical. A sigma-concave/convex-horizontal trisegmental 3BL was the most common phenotype (27%). Globally, the sigma-concave/convex pattern was present in 42%. The 3BL adhered the ethmoidal bulla in 87%. The segmenting method is eligible to describe the 3BL's sophisticated morphology.

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs.

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an unmet clinical need for prevention and therapy of post-myocardial infarction heart failure (post-MI HF). Clinically relevant pig models of post-MI HF are prerequisites for final proof-of-concept studies before entering into clinical trials in drug and medical device development. Here we aimed to characterize a closed-chest porcine model of post-MI HF in adult Göttingen minipigs with long-term follow-up including serial cardiac magnetic resonance imaging (CMRI) and to compare it with the commonly used Landrace pig model. MI was induced by intraluminal balloon occlusion of the left anterior descending coronary artery for 120 min in Göttingen minipigs and for 90 min in Landrace pigs, followed by reperfusion. CMRI was performed to assess cardiac morphology and function at baseline in both breeds and at 3 and 6 months in Göttingen minipigs and at 2 months in Landrace pigs, respectively. Scar sizes were comparable in the two breeds, but MI resulted in a significant decrease of left ventricular ejection fraction (LVEF) only in Göttingen minipigs, while Landrace pigs did not show a reduction of LVEF. Right ventricular (RV) ejection fraction increased in both breeds despite the negligible RV scar sizes. In contrast to the significant increase of left ventricular end-diastolic (LVED) mass in Landrace pigs at 2 months, Göttingen minipigs showed a slight increase in LVED mass only at 6 months. In summary, this is the first characterization of post-MI HF in Göttingen minipigs in comparison to Landrace pigs, showing that the Göttingen minipig model reflects post-MI HF parameters comparable to the human pathology. We conclude that the Göttingen minipig model is superior to the Landrace pig model to study the development of post-MI HF.

Creating a cross-sectional, CT and MR atlas of the Pannon minipig.

PURPOSE: The purpose of this study was to create a detailed cross-sectional anatomical reference atlas of the Pannon minipig by correlating good resolution CT and MR images with high quality cross-sectional anatomical images. According to the authors knowledge, no detailed anatomical atlas is available for the minipig. MATERIAL AND METHOD: An adult female minipig was utilized for this purpose. The animal was placed in a PVC half tube, and CT generated images of 0.6 mm slice thickness and MR images of 1.41 mm slice thickness were obtained. The images covered the whole body from the most rostral portion of the snout to the tip of the tail. The CT and MR scans were aligned with frozen anatomical sections prepared with an anatomical band saw from the same animal and significant structures were identified and labelled. The terminology employed has been referenced from the Nomina Anatomica Veterinaria 6th edition-2017. FINDINGS AND CONCLUSIONS: The resulting atlas consists of 109 anatomical slices and the corresponding 109 CT and 109 MR scans (altogether 327 images) and the nomenclature list for each image. Although this publication contains limited images of the resulted atlas, it is a reference source for anatomy education and clinical sciences. We are of the opinion that more comprehensive and especially online available interactive atlases should be prepared using similar methodology.

Digital Endocasting in Comparative Canine Brain Morphology.

Computed tomography (CT) is one of the most useful techniques for digitizing bone structures and making endocranial models from the neurocranium. The resulting digital endocasts reflect the morphology of the brain and the associated structures. Our first aim was to document the methodology behind creating detailed digital endocasts of canine skulls. We created digital endocasts of the skulls of 24 different dog breeds and 4 wild canids for visualization and teaching purposes. We used CT scanning with 0.323 mm × 0.322 mm × 0.6 mm resolution. The imaging data were segmented with 3D Slicer software and refined with Autodesk Meshmixer. Images were visualized in 3D Slicer and surface models were converted to 3D PDFs to provide easier interactive access, and 3D prints were also generated for visualization purposes. Our second aim was to analyze how skull length and width relate to the surface areas of the prepiriform rhinencephalic, prefrontal, and non-prefrontal cerebral convexity areas of the endocasts. The rhinencephalic area ratio decreased with a larger skull index. Our results open the possibility to analyze the relationship between the skull and brain morphology, and to link certain features to behavior, and cognition in dogs.

A different technique for sutureless coronary bypass grafting.

Introduction: Many coronary anastomotic devices have been designed to replace manual stitching in coronary surgery; however, interestingly, none of them became widespread. Our aim was to work out an easy and fast endoluminal vessel-to-vessel stent bridge distal anastomotic technique. Materials and methods: Ten coronary arteries of eight fresh human hearts were used in this study. The anastomosis was performed with the implantation of a graft vessel into the lumen of the coronary artery by performing stent fixation. The technique is described and photo documented in detail. The durability and the conductibility of the anastomosis were examined with intraluminal endoscopy, functional streaming test, and a coloring of the vessels. Results: The anastomosis had great results in all cases. Obstruction, dissection, or dislocation of the vessels was not observable. Conclusions: This study confirmed the ex-vivo feasibility of the described technique. This method can be an easy, fast, and reliable method applied in the endoscopic distal coronary artery anastomosis surgery. The development of stents adapted to this method and the in-vivo testing of this technique are necessary for the future.

MRI, CT and high resolution macro-anatomical images with cryosectioning of a Beagle brain: Creating the base of a multimodal imaging atlas.

Most common methods that directly show macro- or microscopic anatomy of the brain usually require the removal of the organ from the neurocranium. However, the brain can be revealed in situ by using proper sectioning techniques. Our aim was to both improve the cryosectioning method, test its limits and create a high-resolution macro-anatomical image series of a Beagle brain, which at the time of the study did not exist. A two-year-old female Beagle has been scanned with CT and MRI ante and post mortem, then the arteries of the head were filled with red resin. After freezing to -80°C, a neurocranium block was created and was embedded into a water-gelatin mix. Using a special milling device and a DSLR camera, 1112 consecutive RGB-color cryosections were made with a 100 µm layer thickness and captured in high resolution (300 dpi, 24-bit color, and pixel size was 19.5 x 19.5 µm). Image post-processing was done with Adobe Photoshop CS3 and Thermo Scientific Amira 6.0 softwares, and as a result of the proper alignment and coregistration, visualization and comparing was possible with all the applied imaging modalities (CT, MRI, cryosectioning) in any arbitrary plane. Surface models from the arteries, veins, brain and skull were also generated after segmentation in the same coordinate system, giving a unique opportunity for comparing the two-dimensional and three-dimensional anatomy. This is the first study which focuses directly to this high-definition multimodal visualization of the canine brain, and it provides the most accurate results compared to previous cryosectioning studies, as using an improved method, higher image quality, more detailed image, proper color fidelity and lower artefact formation were achieved. Based on the methodology we described, it can serve as a base for future multimodal (CT, MR, augmented- or virtual reality) imaging atlases for medical, educational and scientific purposes.

Transcriptional Alterations by Ischaemic Postconditioning in a Pig Infarction Model: Impact on Microvascular Protection.

Although the application of cardioprotective ischaemia/reperfusion (I/R) stimuli after myocardial infarction (MI) is a promising concept for salvaging the myocardium, translation to a clinical scenario has not fulfilled expectations. We have previously shown that in pigs, ischaemic postconditioning (IPostC) reduces myocardial oedema and microvascular obstruction (MVO), without influencing myocardial infarct size. In the present study, we analyzed the mechanisms underlying the IPostC-induced microvascular protection by transcriptomic analysis, followed by pathway analysis. Closed-chest reperfused MI was induced by 90 min percutaneous balloon occlusion of the left anterior descending coronary artery, followed by balloon deflation in anaesthetised pigs. Animals were randomised to IPostC (n = 8), MI (non-conditioned, n = 8), or Control (sham-operated, n = 4) groups. After three hours or three days follow-up, myocardial tissue samples were harvested and subjected to RNA-seq analysis. Although the transcriptome analysis revealed similar expression between IPostC and MI in transcripts involved in cardioprotective pathways, we identified gene expression changes responding to IPostC at the three days follow-up. Focal adhesion signaling, downregulated genes participating in cardiomyopathy and activation of blood cells may have critical consequences for microvascular protection. Specific analyses of the gene subsets enriched in the endothelium of the infarcted area, revealed strong deregulation of transcriptional functional clusters, DNA processing, replication and repair, cell proliferation, and focal adhesion, suggesting sustentative function in the endothelial cell layer protection and integrity. The spatial and time-dependent transcriptome analysis of porcine myocardium supports a protective effect of IPostC on coronary microvasculature post-MI.

A detailed canine brain label map for neuroimaging analysis.

BACKGROUND AND AIMS: Dogs have recently become an important model species for comparative social and cognitive neuroscience. Brain template-related label maps are essential for functional magnetic resonance imaging (fMRI) data analysis, to localize neural responses. In this study, we present a detailed, individual-based, T1-weighted MRI-based brain label map used in dog neuroimaging analysis. METHODS: A typical, medium-headed dog (a 7.5-year-old male Golden Retriever) was selected from a cohort of 22 dogs, based on brain morphology (shape, size, and gyral pattern), to serve as the template for a label map. RESULTS: Eighty-six 3-dimensional labels were created to highlight the main cortical (cerebral gyri on the lateral and medial side) and subcortical (thalamus, caudate nucleus, amygdala, and hippocampus) structures of the prosencephalon and diencephalon, and further main parts of brainstem (mesencephalon and rhombencephalon). DISCUSSION: Importantly, this label map is (a) considerably more detailed than any available dog brain template; (b) it is easy to use with freeware and commercial neuroimaging software for MRI and fMRI analysis; and (c) it can be registered to other existing templates, including a recent average-based dog brain template. Using the coordinate system and label map proposed here can enhance precision and standard localization during future canine neuroimaging studies.

Matrix Metalloproteinase-2 Impairs Homing of Intracoronary Delivered Mesenchymal Stem Cells in a Porcine Reperfused Myocardial Infarction: Comparison With Intramyocardial Cell Delivery.

BACKGROUND: Intracoronary (IC) injection of mesenchymal stem cells (MSCs) results in a prompt decrease of absolute myocardial blood flow (AMF) with late and incomplete recovery of myocardial tissue perfusion. Here, we investigated the effect of decreased AMF on oxidative stress marker matrix metalloproteinase-2 (MMP-2) and its influence on the fate and homing and paracrine character of MSCs after IC or intramyocardial cell delivery in a closed-chest reperfused myocardial infarction (MI) model in pigs. METHODS: Porcine MSCs were transiently transfected with Ad-Luc and Ad-green fluorescent protein (GFP). One week after MI, the GFP-Luc-MSCs were injected either IC (group IC, 11.00 ± 1.07 × 106) or intramyocardially (group IM, 9.88 ± 1.44 × 106). AMF was measured before, immediately after, and 24 h post GFP-Luc-MSC delivery. In vitro bioluminescence signal was used to identify tissue samples containing GFP-Luc-MSCs. Myocardial tissue MMP-2 and CXCR4 receptor expression (index of homing signal) were measured in bioluminescence positive and negative infarcted and border, and non-ischemic myocardial areas 1-day post cell transfer. At 7-day follow-up, myocardial homing (cadherin, CXCR4, and stromal derived factor-1alpha) and angiogenic [fibroblast growth factor 2 (FGF2) and VEGF] were quantified by ELISA of homogenized myocardial tissues from the bioluminescence positive and negative infarcted and border, and non-ischemic myocardium. Biodistribution of the implanted cells was quantified by using Luciferase assay and confirmed by fluorescence immunochemistry. Global left ventricular ejection fraction (LVEF) was measured at baseline and 1-month post cell therapy using magnet resonance image. RESULTS: AMF decreased immediately after IC cell delivery, while no change in tissue perfusion was found in the IM group (42.6 ± 11.7 vs. 56.9 ± 16.7 ml/min, p = 0.018). IC delivery led to a significant increase in myocardial MMP-2 64 kD expression (448 ± 88 vs. 315 ± 54 intensity × mm2, p = 0.021), and decreased expression of CXCR4 (592 ± 50 vs. 714 ± 54 pg/tissue/ml, p = 0.006), with significant exponential decay between MMP-2 and CXCR4 (r = 0.679, p < 0.001). FGF2 and VEGF of the bioluminescence infarcted and border zone of homogenized tissues were significantly elevated in the IM goups as compared to IC group. LVEF increase was significantly higher in IM group (0.8 ± 8.4 vs 5.3 ± 5.2%, p = 0.046) at the 1-month follow up. CONCLUSION: Intracoronary stem cell delivery decreased AMF, with consequent increase in myocardial expression of MMP-2 and reduced CXCR4 expression with lower level of myocardial homing and angiogenic factor release as compared to IM cell delivery.

Linear relationship found by magnetic resonance imaging between cerebrospinal fluid volume and body weight in dogs.

Despite numerous studies on cerebrospinal fluid (CSF) and its importance during hydrocephalus or myelography, no reliable values exist about its overall volume in dogs. In this study, our aim was to measure the intracranial (IC) volume of CSF in dogs and assess its possible relationship with body size and the symmetry of the lateral ventricles. We ran a 3D magnetic resonance imaging (MRI) sequence on the central nervous system of 12 healthy, male mongrel dogs between 3-5 years of age and 7.5-35.0 kg body weight. A validated semiautomatic segmentation protocol was implemented to segment the CSF and measure its volume. Values for the volume of the ventricular compartment were between 0.97 and 2.94 ml, with 62.1 ± 11.7% in the lateral ventricles, 17.6 ± 4.9% in the third ventricle, 4.9 ± 1.6% in the aqueductus mesencephali and 15.5 ± 6.6% in the fourth ventricle. In 11 cases a significant asymmetry was found between the lateral ventricles. The results suggest that it may be normal for a dog to have one of the lateral ventricles 1.5 times larger than the other. The correlation between body weight and CSF volume was linear, indicating that the current dosage protocols for myelography, based on a hypothetical proportional relationship with body weight, may have to be revised.

COMPARISON BETWEEN MAGNETIC RESONANCE IMAGING ESTIMATES OF EXTRACRANIAL CEREBROSPINAL FLUID VOLUME AND PHYSICAL MEASUREMENTS IN HEALTHY DOGS.

Dosages for myelography procedures in dogs are based on a hypothetical proportional relationship between bodyweight and cerebrospinal fluid (CSF) volume. Anecdotal radiographic evidence and recent studies have challenged the existence of such a defined relationship in dogs. The objectives of this prospective cross-sectional study were to describe CSF volumes using magnetic resonance imaging (MRI) in a group of clinically healthy dogs, measure the accuracy of MRI CSF volumes, and compare MRI CSF volumes with dog physical measurements. A sampling perfection with application optimized contrast using different flip-angle evolution MRI examination of the central nervous system was carried out on 12 healthy, male mongrel dogs, aged between 3 and 5 years with a bodyweight range of 7.5-35.0 kg. The images were processed with image analysis freeware (3D Slicer) in order to calculate the volume of extracranial CSF. Cylindrical phantoms of known volume were included in scans and used to calculate accuracy of MRI volume estimates. The accuracy of MRI volume estimates was 99.8%. Extracranial compartment CSF volumes ranged from 20.21 to 44.06 ml. Overall volume of the extracranial CSF increased linearly with bodyweight, but the proportional volume (ml/bodyweight kilograms) of the extracranial CSF was inversely proportional to bodyweight. Relative ratios of volumes in the cervical, thoracic, and lumbosacral regions were constant. Findings indicated that the current standard method of using body weight to calculate dosages of myelographic contrast agents in dogs may need to be revised.

Preclinical randomised safety, efficacy and physiologic study of the silicon dioxide inert-coated Axetis and bare metal stent: short-, mid- and long-term outcome.

AIMS: To evaluate the short-, mid- and long-term safety, efficacy and vascular physiology of Axetis silicon dioxide (SiO2, abrading the micropores) inert-coated stent implantation in a randomised preclinical setting. METHODS AND RESULTS: Coronary arteries of domestic pigs were randomised to receive either Axetis or BMS (same design) stents with one-, three- and six-month follow-up (FUP), controlled by coronary angiography, optical coherence tomography (OCT), intravascular ultrasound (IVUS) and histology (n=32). The time-dependent vasomotor reaction of coronary arteries to stenting was measured using modified myography (n=12). Complete endothelialisation of the Axetis stent was confirmed by OCT, IVUS and histology at one-month FUP. Histopathology revealed continuous healing of the vessel wall with a gradual reduction of inflammation and fibrin score during the six-month FUP in both stent types. Significantly smaller neointimal area and %area stenosis were measured in Axetis stents compared with BMS at each FUP time point. Vascular reactivity measurements showed significantly better endothelium-dependent vasodilation of stented arteries with Axetis implantation. CONCLUSIONS: Implantation of the Axetis SiO2-coated stent resulted in a significantly better safety, efficacy and vessel physiology profile compared with BMS of the same design with a continuous decrease in vessel inflammation during the six-month FUP.

Long-acting beneficial effect of percutaneously intramyocardially delivered secretome of apoptotic peripheral blood cells on porcine chronic ischemic left ventricular dysfunction.

The quantity of cells with paracrine effects for use in myocardial regeneration therapy is limited. This study investigated the effects of catheter-based endomyocardial delivery of secretome of 2.5 × 10(9) apoptotic peripheral blood mononuclear cells (APOSEC) on porcine chronic post-myocardial infarction (MI) left ventricular (LV) dysfunction and on gene expression. Closed-chest reperfused MI was induced in pigs by 90-min occlusion followed by reperfusion of the mid-LAD (day 0). At day 30, animals were randomized to receive porcine APOSEC (n = 8) or medium solution (control; n = 8) injected intramyocardially into the MI border zone using 3D NOGA guidance. At day 60, cardiac MRI with late enhancement and diagnostic NOGA (myocardial viability) were performed. Gene expression profiling of the infarct core, border zone, and normal myocardium was performed using microarray analysis and confirmed by quantitative real-time PCR. Injection of APOSEC significantly decreased infarct size (p < 0.05) and improved cardiac index and myocardial viability compared to controls. A trend towards higher LV ejection fraction was observed in APOSEC vs. controls (45.4 ± 5.9% vs. 37.4 ± 8.9%, p = 0.052). Transcriptome analysis revealed significant downregulation of caspase-1, tumor necrosis factor and other inflammatory genes in APOSEC-affected areas. rtPCR showed higher expression of myogenic factor Mefc2 (p < 0.05) and downregulated caspase genes (p < 0.05) in APOSEC-treated pigs. In conclusion, overexpression of MEF2c and repression of caspase was related to decreased infarct size and improved cardiac function in secretome-treated animals. Altered gene expression 1-month post-APOSEC treatment proved the long-acting effects of cell-free therapy with paracrine factors.

Valvuloplasty with a paclitaxel-eluting balloon prevents restenosis in an experimental animal model of aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Restenosis occurs invariably within 12 months following balloon valvuloplasty (BAV) in calcific aortic valve disease (CAVD), and is a limiting factor of this treatment. Cellular proliferation secondary to balloon injury is thought to play a pivotal role in the mechanism of restenosis. The study aim was to investigate the potential role of a paclitaxel-eluting valvuloplasty balloon to mitigate the progression of restenosis in an animal model of CAVD. METHODS: Fifty-three rabbits were fed with an aortic stenosis (AS)-inducing diet (cholesterol 0.5% plus vitamin D3 50,000 IU/day) for three months. The surviving animals (n = 40) underwent echocardiographic and invasive assessments, followed by valvuloplasty, randomly using either a paclitaxel-coated (3 µg/mm2) or a plain balloon. At one month after BAV, the surviving animals (n = 28) underwent repeat assessments, followed by histology and micro-computed tomography (MicroCT) analysis of the aortic valve. RESULTS: The baseline and post-BAV transvalvular gradients, aortic valve area (AVA), left ventricular stroke work loss (SWL) and aortic valve resistance (AVR) were similar between the groups (14 rabbits were assigned to paclitaxel-eluting, and 14 to plain balloon). Significant differences between the groups were observed at one-month post-BAV, which was suggestive of diminished restenosis in the paclitaxel-balloon group (mean maximum transvalvular pressure gradient 7.7 ± 7.7 versus 3.6 ± 3.7 mmHg, p = 0.08; AVA 0.91 ± 0.59 versus 0.55 ± 0.22 cm2, p = 0.04; SWL 3.5 ± 4.0 versus 8.6 ± 8.0%, p = 0.047; AVR 86 ± 71 versus 177 ± 137 dynes/s/cm(-5), p = 0.039). Histology demonstrated decreased leaflet thickness (0.60 ± 0.15 versus 0.71 ± 0.17 mm, p = 0.03), proliferating cell nuclear antigen (PCNA) staining (grade 1.53 ± 0.04 versus 2.24 ± 0.55, p = 0.049), and calcification in the paclitaxel-balloon group. CONCLUSION: Use of a paclitaxel-eluting valvuloplasty balloon in an animal model of AS resulted in attenuated restenosis, secondary to decrease in valve proliferation and calcification.