dP/dt: An underestimated prognostic factor in large animal infarction model.

The present study aims to establish a reproducible large animal experimental unit using a minipig model to monitor cardiac function changes. A 90-min closed-chest balloon occlusion of the left anterior descending branch of the coronary artery was used to induce myocardial infarction in Pannon minipigs. To monitor the cardiac function, measurements were made by cardiac magnetic resonance imaging (cMRI), invasive pressure monitoring, and a Pulse index Continuous Cardiac Output (PiCCO) hemodynamic system at 0, 72, and 720 h during the follow-up period.

Adaptation of closed-chest infarction porcine model to adult Pannon minipigs.

The aim of the recent study was to collect data on the genotype characteristics of the Hungarian self-bred Pannon minipigs by adapting a standardized infarct model procedure. Closed chest AMI was induced by balloon occlusion for 90 min in the left anterior descendent coronary artery (LAD) in 24 adult intact female minipigs followed by reperfusion. To assess the left ventricular (LV) function, serial cardiac magnetic resonance imaging (cMRI) was performed prior to the experimental procedure, on day 3 post-AMI (72 ± 12 h), and at 1 month follow-up (Day 30 ± 2 days).

Peri-Interventional Triple Therapy with Dabigatran Modifies Vasomotion after Bare-Metal Stent Implantation in a Pig Coronary Artery Model.

(1) Background: Coronary artery stenting leads to local inflammation, disturbs vasomotion, and slows endothelialization, increasing vascular thrombus risk. We used a pig stenting coronary artery model to assess how peri-interventional triple therapy with dabigatran ameliorates these effects. (2) Methods: In a total of 28 pigs bare-metal stents were implanted.

Peri-interventional Triple Therapy With Dabigatran Improves Vasomotion and Promotes Endothelialization in Porcine Coronary Stenting Model.

We evaluated the short and long-term effect of peri-interventional dabigatran therapy on vasomotion, endothelialization, and neointimal formation in a porcine coronary artery stenting model. Stenting of coronary arteries induces local inflammation, impairs vasomotion and delays endothelialization. Twenty-eight animals underwent percutaneous coronary intervention (PCI) with drug eluting stents.

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.

Hippocampal size did not differ between epileptic and non-epileptic dogs using volumetric and subjective methods.

Hippocampal changes in epilepsy may manifest as hippocampal atrophy/sclerosis. A recent human study suggests that the demonstration of hippocampal volume loss is more reliable using quantitative evaluation methods. The aim of the present study was to obtain volumetric data in both epileptic and healthy dogs, to compare hippocampal volumes in both groups, and to compare subjective and volumetric assessment.

CDR132L improves systolic and diastolic function in a large animal model of chronic heart failure.

Aims: Cardiac miR-132 activation leads to adverse remodelling and pathological hypertrophy. CDR132L is a synthetic lead-optimized oligonucleotide inhibitor with proven preclinical efficacy and safety in heart failure (HF) early after myocardial infarction (MI), and recently completed clinical evaluation in a Phase 1b study (NCT04045405). The aim of the current study was to assess safety and efficacy of CDR132L in a clinically relevant large animal (pig) model of chronic heart failure following MI.

Preclinical development of a miR-132 inhibitor for heart failure treatment.

Despite proven efficacy of pharmacotherapies targeting primarily global neurohormonal dysregulation, heart failure (HF) is a growing pandemic with increasing burden. Treatments mechanistically focusing at the cardiomyocyte level are lacking. MicroRNAs (miRNA) are transcriptional regulators and essential drivers of disease progression.

Discovery and development of extreme selective inhibitors of the ITD and D835Y mutant FLT3 kinases.

Aberrant activation of FMS-like tyrosine receptor kinase 3 (FLT3) is implicated in the pathogenesis of acute myeloid leukemia (AML) in 20-30% of patients. In this study we identified a highly selective (phenylethenyl)quinazoline compound family as novel potent inhibitors of the FLT3-ITD and FLT3-D835Y kinases. Their prominent effects were confirmed by biochemical and cellular proliferation assays followed by mice xenograft studies.

A Recurrent Suprapituitary Ependymal Cyst Managed by Endoscopy-Assisted Transsphenoidal Surgery in a Canine: A Case Report.

A 9-years-old spayed female mixed-breed dog was referred for the evaluation of intermittent head tremors, obtundation, long-standing blindness, and a tendency to seek confined spaces. The dog lost its vision 6 months before the current presentation. A menace response was absent on ophthalmological examination.

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.

Discovery of N-[4-(Quinolin-4-yloxy)phenyl]benzenesulfonamides as Novel AXL Kinase Inhibitors.

The overexpression of AXL kinase has been described in many types of cancer. Due to its role in proliferation, survival, migration, and resistance, AXL represents a promising target in the treatment of the disease. In this study we present a novel compound family that successfully targets the AXL kinase.

Porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertension.

Background: Meaningful translational large animal models for cardiac diseases are indispensable for studying disease mechanisms, development of novel therapeutic strategies, and evaluation of potential drugs.

Methods: For induction of heart failure, cardiac hypertrophy and fibrosis, a bare metal stent was implanted in the descending aorta of growing pigs (n = 7), inducing pressure stress on the left ventricle (group HYPI). The constant stent size in growing pigs resulted in antegrade partial obstruction of the aortic flow with a gradual increase in afterload.

Intrinsic remote conditioning of the myocardium as a comprehensive cardiac response to ischemia and reperfusion.

We have previously shown that distal anterior wall ischemia/reperfusion induces gene expression changes in the proximal anterior myocardial area, involving genes responsible for cardiac remodeling. Here we investigated the molecular signals of the ischemia non-affected remote lateral and posterior regions and present gene expression profiles of the entire left ventricle by using our novel and straightforward method of 2D and 3D image reconstruction. Five or 24h after repetitive 10min ischemia/reperfusion without subsequent infarction, pig hearts were explanted and myocardial samples from 52 equally distributed locations of the left ventricle were collected.

Novel approach to magnetic resonance imaging of epileptic dogs - T2 relaxometry of the brain with emphasised hippocampus.

Hippocampal sclerosis is the most common imaging finding of intractable human epilepsy, and it may play an important role in canine and feline epileptogenesis and seizure semiology, too. The magnetic resonance imaging (MRI) criteria of hippocampal sclerosis are T2 hyperintensity, shrinkage and loss of internal structure. The detection of these changes is often challenging by subjective visual assessment of qualitative magnetic resonance (MR) images.

In vivo MRI and ex vivo histological assessment of the cardioprotection induced by ischemic preconditioning, postconditioning and remote conditioning in a closed-chest porcine model of reperfused acute myocardial infarction: importance of microvasculature.

Background: Cardioprotective value of ischemic post- (IPostC), remote (RIC) conditioning in acute myocardial infarction (AMI) is unclear in clinical trials. To evaluate cardioprotection, most translational animal studies and clinical trials utilize necrotic tissue referred to the area at risk (AAR) by magnetic resonance imaging (MRI). However, determination of AAR by MRI' may not be accurate, since MRI-indices of microvascular damage, i.

Sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling.

We have analyzed the pathway networks of ischemia-affected and remote myocardial areas after repetitive ischemia/reperfusion (r-I/R) injury without ensuing myocardial infarction (MI) to elaborate a spatial- and chronologic model of cardioprotective gene networks to prevent left ventricular (LV) adverse remodeling. Domestic pigs underwent three cycles of 10/10 min r-I/R by percutaneous intracoronary balloon inflation/deflation in the mid left anterior descending artery, without consecutive MI. Sham interventions (n = 8) served as controls.

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.

Design and synthesis of new imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrazine derivatives with antiproliferative activity against melanoma cells.

Melanoma is an aggressive form of skin cancer and it is generally associated with poor prognosis in patients with late-stage disease. Due to the increasing occurrence of melanoma, there is a need for the development of novel therapies. A new series of diarylamide and diarylurea derivatives containing imidazo[1,2-a]pyridine or imidazo[1,2-a]pyrazine scaffold was designed and synthesized to investigate their in vitro efficacy against the A375P human melanoma cell line.

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.

Experimental results of using autologous rectus fascia sheath for venous patch grafts in dogs.

Autologous vascular patch grafts developed from the internal rectus sheath were implanted onto the bilateral common iliac vein and jugular vein of 4 experimental beagle dogs. During the development and implanting of the grafts no technical difficulties or perioperative complications were encountered. The follow-up lasted 6 months and 3 months in the case of the common iliac vein grafts and the jugular grafts, respectively.

Technical feasibility of transperineal MR-guided prostate interventions in a low-field open MRI unit: canine study.

Magnetic resonance imaging (MRI) provides superior visualization of the prostate, its substructure, surrounding tissues, and, most important, focal lesions or cancer. The purpose of our canine study was to demonstrate the feasibility of a low-field (0.35 T) transperineal system that enables precise MR image guidance of prostate interventions.

Platelet activation and high tissue factor level predict acute stent thrombosis in pig coronary arteries: prothrombogenic response of drug-eluting or bare stent implantation within the first 24 hours.

Increased thrombogenicity of drug-eluting stents (DESs) has recently been reported. The aim of the present study was to investigate the prothrombogenic effect of DESs and Bare stents, and determine factors predictive of acute stent thrombosis (AST) in preclinical experiments using new stent design or coating. Circulating pre- and post-stenting parameters of platelet activation (mean platelet volume, MPV; platelet distribution width, platelet large cell ratio), thrombin activation (thrombin-antithrombin complex, TAT and prothrombin fragments, F1+2), tissue factor antigen (TF-ag) and -activity (TF-act) and plasminogen activator inhibitor-1 (PAI-1) were measured in 141 consecutive pigs.

Magnetic resonance imaging technique for the examination of canine mammary tumours.

The aim of this study was to adapt the human magnetic resonance imaging (MRI) sequences for use in the routine examination of canine mammary glands. MRI was performed on 10, middle- to old-aged dogs of different breeds. It was found that T1- and T2-weighted spin echo, short T1 inversion recovery sequences and a gradient echo (GE) dynamic T1-weighted measurement made in the coronal and transversal planes were the most informative MR diagnostic methods for imaging canine mammary tumours.

Paradoxical effects of aurintricarboxylic acid and RG-13577: acute thrombosis and in-stent stenosis in a passive-coated stent.

Purpose: To investigate if a platelet inhibitor (aurintricarboxylic acid [ATA]) and a heparin-mimicking antagonist (RG-13577) of basic fibroblast growth factor 2 (bFGF2) could be combined as a stable compound and attached to conventional bare metal stents to hinder thrombus formation and inflammatory reactions of stenting.

Methods: Fifteen domestic pigs were stented with RG-13577/ATA-coated (n=6), ATA-coated (n=12), and bare metal stents (n=12) in the left anterior descending (LAD) and left circumflex (LCX) coronary arteries. All surviving pigs were evaluated with contrast angiography and intravascular ultrasonography (IVUS) after 4 weeks.