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  1. Article ; Online: Pathology and Advanced Imaging—Characterization of a Congenital Cardiac Defect and Complex Hemodynamics in a Pig

    Alexandra J. Malbon / Miriam Weisskopf / Lukas Glaus / Sebastian Neuber / Maximilian Y. Emmert / Christian T. Stoeck / Nikola Cesarovic

    Frontiers in Veterinary Science, Vol

    A Case Report

    2021  Volume 8

    Abstract: Domestic pigs are widely used in cardiovascular research as the porcine circulatory system bears a remarkable resemblance to that of humans. In order to reduce variability, only clinically healthy animals enter the study as their health status is ... ...

    Abstract Domestic pigs are widely used in cardiovascular research as the porcine circulatory system bears a remarkable resemblance to that of humans. In order to reduce variability, only clinically healthy animals enter the study as their health status is assessed in entry examination. Like humans, pigs can also suffer from congenital heart disease, such as an atrial septal defect (ASD), which often remains undetected. Due to the malformation of the endocardial cushion during organ development, mitral valve defects (e.g., mitral clefts) are sometimes associated with ASDs, further contributing to hemodynamic instability. In this work, we report an incidental finding of a hemodynamically highly relevant ASD in the presence of incompetent mitral and tricuspid valves, in an asymptomatic, otherwise healthy juvenile pig. In-depth characterization of the cardiac blood flow by four-dimensional (4D) flow magnetic resonance imaging (MRI) revealed a prominent diastolic left-to-right and discrete systolic right-to-left shunt, resulting in a pulmonary-to-systemic flow ratio of 1.8. Severe mitral (15 mL/stroke) and tricuspid (22 mL/stroke) regurgitation further reduced cardiac output. Pathological examination confirmed the presence of an ostium primum ASD and found a serous cyst of lymphatic origin that was filled with clear fluid partially occluding the ASD. A large mitral cleft was identified as the most likely cause of severe regurgitation, and histology showed mild to moderate endocardiosis in the coaptation area of both atrio-ventricular valves. In summary, although not common, congenital heart defects could play a role as a cause of experimental variability or even intra-experimental mortality when working with apparently heathy, juvenile pigs.
    Keywords large animal models ; cardiovascular imaging ; congenital heart defects ; cardiovascular pathology ; atrial septal defect ; blood flow ; Veterinary medicine ; SF600-1100
    Subject code 610
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Dos and don'ts in large animal models of aortic insufficiency

    Miriam Weisskopf / Lukas Glaus / Nina E. Trimmel / Melanie M. Hierweger / Andrea S. Leuthardt / Marian Kukucka / Thorald Stolte / Christian T. Stoeck / Volkmar Falk / Maximilian Y. Emmert / Markus Kofler / Nikola Cesarovic

    Frontiers in Veterinary Science, Vol

    2022  Volume 9

    Abstract: Aortic insufficiency caused by paravalvular leakage (PVL) is one of the most feared complications following transcatheter aortic valve replacement (TAVI) in patients. Domestic pigs (Sus scrofa domestica) are a popular large animal model to study such ... ...

    Abstract Aortic insufficiency caused by paravalvular leakage (PVL) is one of the most feared complications following transcatheter aortic valve replacement (TAVI) in patients. Domestic pigs (Sus scrofa domestica) are a popular large animal model to study such conditions and develop novel diagnostic and therapeutic techniques. However, the models based on prosthetic valve implantation are time intensive, costly, and often hamper further hemodynamic measurements such as PV loop and 4D MRI flow by causing implantation-related wall motion abnormalities and degradation of MR image quality. This study describes in detail, the establishment of a minimally invasive porcine model suitable to study the effects of mild-to-moderate “paravalvular“ aortic regurgitation on left ventricular (LV) performance and blood flow patterns, particularly under the influence of altered afterload, preload, inotropic state, and heart rate. Six domestic pigs (Swiss large white, female, 60–70 kg of body weight) were used to establish this model. The defects on the hinge point of aortic leaflets and annulus were created percutaneously by the pierce-and-dilate technique either in the right coronary cusp (RCC) or in the non-coronary cusp (NCC). The hemodynamic changes as well as LV performance were recorded by PV loop measurements, while blood flow patterns were assessed by 4D MRI. LV performance was additionally challenged by pharmaceutically altering cardiac inotropy, chronotropy, and afterload. The presented work aims to elaborate the dos and don'ts in porcine models of aortic insufficiency and intends to steepen the learning curve for researchers planning to use this or similar models by giving valuable insights ranging from animal selection to vascular access choices, placement of PV Loop catheter, improvement of PV loop data acquisition and post-processing and finally the induction of paravalvular regurgitation of the aortic valve by a standardized and reproducible balloon induced defect in a precisely targeted region of the aortic valve.
    Keywords large animal model ; aortic valve ; paravalvular leakage ; aortic insufficiency (AI) ; Minimally invasive ; PV loop ; Veterinary medicine ; SF600-1100
    Subject code 621
    Language English
    Publishing date 2022-09-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Functional, Metabolic and Morphologic Results of Ex Vivo Donor Lung Perfusion with a Perfluorocarbon-Based Oxygen Carrier Nanoemulsion in a Large Animal Transplantation Model

    Ilhan Inci / Stephan Arni / Ilker Iskender / Necati Citak / Josep Monné Rodriguez / Miriam Weisskopf / Isabelle Opitz / Walter Weder / Thomas Frauenfelder / Marie Pierre Krafft / Donat R. Spahn

    Cells, Vol 9, Iss 2501, p

    2020  Volume 2501

    Abstract: Background: Ex vivo lung perfusion (EVLP) is a technology that allows the re-evaluation of questionable donor lung before implantation and it has the potential to repair injured donor lungs that are otherwise unsuitable for transplantation. We ... ...

    Abstract Background: Ex vivo lung perfusion (EVLP) is a technology that allows the re-evaluation of questionable donor lung before implantation and it has the potential to repair injured donor lungs that are otherwise unsuitable for transplantation. We hypothesized that perfluorocarbon-based oxygen carrier, a novel reconditioning strategy instilled during EVLP would improve graft function. Methods: We utilized perfluorocarbon-based oxygen carrier (PFCOC) during EVLP to recondition and improve lung graft function in a pig model of EVLP and lung transplantation. Lungs were retrieved and stored for 24 h at 4 °C. EVLP was done for 6 h with or without PFCOC. In the transplantation groups, left lung transplantation was done after EVLP with or without PFCOC. Allograft function was assessed by means of pulmonary gas exchange, lung mechanics and vascular pressures, histology and transmission electron microscopy (TEM). Results: In the EVLP only groups, physiological and biochemical markers during the 6-h perfusion period were comparable. However, perfusate lactate potassium levels were lower and ATP levels were higher in the PFCOC group. Radiologic assessment revealed significantly more lung infiltrates in the controls than in the PFCOC group ( p = 0.04). In transplantation groups, perfusate glucose consumption was higher in the control group. Lactate levels were significantly lower in the PFCOC group ( p = 0.02). Perfusate flavin mononucleotide (FMN) was significantly higher in the controls ( p = 0.008). Post-transplant gas exchange was significantly better during the 4-h reperfusion period in the PFCOC group ( p = 0.01). Plasma IL-8 and IL-12 levels were significantly lower in the PFCOC group ( p = 0.01, p = 0.03, respectively). ATP lung tissue levels at the end of the transplantation were higher and myeloperoxidase (MPO) levels in lung tissue were lower in the PFCOC group compared to the control group. In the PFCOC group, TEM showed better tissue preservation and cellular viability. Conclusion: PFCOC application is safe during ...
    Keywords ex vivo lung perfusion ; oxygen carrier ; perfluorocarbon ; lung transplantation ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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