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  1. Article ; Online: A dumbbell rescue stent graft facilitates clamp-free repair of aortic injury in a porcine model.

    Kenawy, Dahlia M / Elsisy, Moataz / Abdel-Rasoul, Mahmoud / Koppert, Tanner L / Garcia-Neuer, Marlene I / Chun, Youngjae / Tillman, Bryan W

    JVS-vascular science

    2023  Volume 4, Page(s) 100100

    Abstract: Objective: Noncompressible torso hemorrhage is a high-mortality injury. We previously reported improved outcomes with a retrievable rescue stent graft to temporize aortic hemorrhage in a porcine model while maintaining distal perfusion. A limitation was ...

    Abstract Objective: Noncompressible torso hemorrhage is a high-mortality injury. We previously reported improved outcomes with a retrievable rescue stent graft to temporize aortic hemorrhage in a porcine model while maintaining distal perfusion. A limitation was that the original cylindrical stent graft design prohibited simultaneous vascular repair, given the concern for suture ensnarement of the temporary stent. We hypothesized that a modified, dumbbell-shaped design would preserve distal perfusion and also offer a bloodless plane in the midsection, facilitating repair with the stent graft in place and improve the postrepair hemodynamics.
    Methods: In an Institutional Animal Care and Use Committee-approved terminal porcine model, a custom retrievable dumbbell-shaped rescue stent graft (dRS) was fashioned from laser-cut nitinol and polytetrafluoroethylene covering and compared with aortic cross-clamping. Under anesthesia, the descending thoracic aorta was injured and then repaired with cross-clamping (n = 6) or dRS (n = 6). Angiography was performed in both groups. Operations were divided into phases: (1) baseline, (2) thoracic injury with either cross-clamp or dRS deployed, and (3) recovery, after which the clamp or dRS were removed. Target blood loss was 22% to simulate class II or III hemorrhagic shock. Shed blood was recovered with a Cell Saver and reinfused for resuscitation. Renal artery flow rates were recorded at baseline and during the repair phase and reported as a percentage of cardiac output. Phenylephrine pressor requirements were recorded.
    Results: In contrast with cross-clamped animals, dRS animals demonstrated both operative hemostasis and preserved flow beyond the dRS angiographically. Recovery phase mean arterial pressure, cardiac output, and right ventricular end-diastolic volume were significantly higher in dRS animals (
    Conclusions: Compared with aortic cross-clamping, the dRS model demonstrated superior distal perfusion, while also facilitating simultaneous hemorrhage control and aortic repair. This study demonstrates a promising alternative to aortic cross-clamping to decrease distal ischemia and avoid the unfavorable hemodynamics that accompany clamp reperfusion. Future studies will assess differences in ischemic injury and physiological outcomes.
    Clinical relevance: Noncompressible aortic hemorrhage remains a high-mortality injury, and current damage control options are limited by ischemic complications. We have previously reported a retrievable stent graft to allow rapid hemorrhage control, preserved distal perfusion, and removal at the primary repair. The prior cylindrical stent graft was limited by the inability to suture the aorta over the stent graft owing to risk of ensnarement. This large animal study explored a dumbbell retrievable stent with a bloodless plane to allow suture placement with the stent in place. This approach improved distal perfusion and hemodynamics over clamp repair and heralds the potential for aortic repair while avoiding complications.
    Language English
    Publishing date 2023-02-18
    Publishing country United States
    Document type Journal Article
    ISSN 2666-3503
    ISSN (online) 2666-3503
    DOI 10.1016/j.jvssci.2023.100100
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity (AIDN): A Translational Neuroscience Approach.

    Whitaker, Emmett E / Zheng, Christopher Z / Bissonnette, Bruno / Miller, Andrew D / Koppert, Tanner L / Tobias, Joseph D / Pierson, Christopher R / Christofi, Fedias L

    Journal of visualized experiments : JoVE

    2017  , Issue 124

    Abstract: Anesthesia cannot be avoided in many cases when surgery is required, particularly in children. Recent investigations in animals have raised concerns that anesthesia exposure may lead to neuronal apoptosis, known as anesthesia-induced developmental ... ...

    Abstract Anesthesia cannot be avoided in many cases when surgery is required, particularly in children. Recent investigations in animals have raised concerns that anesthesia exposure may lead to neuronal apoptosis, known as anesthesia-induced developmental neurotoxicity (AIDN). Furthermore, some clinical studies in children have suggested that anesthesia exposure may lead to neurodevelopmental deficits later in life. Nonetheless, an ideal animal model for preclinical study has yet to be developed. The neonatal piglet represents a valuable model for preclinical study, as they share a striking number of developmental similarities with humans. The anatomy and physiology of piglets allow for implementation of rigorous human perioperative conditions in both survival and non-survival procedures. Femoral artery catheterization allows for close monitoring, thus enabling prompt correction of any deviation of the piglet's vital signs and chemistries. In addition, there are multiple developmental similarities between piglets and human neonates. The techniques required to use piglets for experimentation will require experience to master. A pediatric anesthesiologist is a critical member of the investigative team. We describe, in a general sense, the appropriate use of a piglet model for neurodevelopmental study.
    Language English
    Publishing date 2017-06-11
    Publishing country United States
    Document type Journal Article
    ISSN 1940-087X
    ISSN (online) 1940-087X
    DOI 10.3791/55193
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Use of a piglet model for the study of anesthetic-induced developmental neurotoxicity (aidn): a translational neuroscience approach

    Whitaker, Emmett E / Zheng, Christopher Z / Bissonnette, Bruno / Miller, Andrew D / Koppert, Tanner L / Tobias, Joseph D / Pierson, Christopher R / Christofi, Fedias L

    Journal of visualized experiments. 2017 June 11, , no. 124

    2017  

    Abstract: Anesthesia cannot be avoided in many cases when surgery is required, particularly in children. Recent investigations in animals have raised concerns that anesthesia exposure may lead to neuronal apoptosis, known as anesthesia-induced developmental ... ...

    Abstract Anesthesia cannot be avoided in many cases when surgery is required, particularly in children. Recent investigations in animals have raised concerns that anesthesia exposure may lead to neuronal apoptosis, known as anesthesia-induced developmental neurotoxicity (AIDN). Furthermore, some clinical studies in children have suggested that anesthesia exposure may lead to neurodevelopmental deficits later in life. Nonetheless, an ideal animal model for preclinical study has yet to be developed. The neonatal piglet represents a valuable model for preclinical study, as they share a striking number of developmental similarities with humans. The anatomy and physiology of piglets allow for implementation of rigorous human perioperative conditions in both survival and non-survival procedures. Femoral artery catheterization allows for close monitoring, thus enabling prompt correction of any deviation of the piglet's vital signs and chemistries. In addition, there are multiple developmental similarities between piglets and human neonates. The techniques required to use piglets for experimentation will require experience to master. A pediatric anesthesiologist is a critical member of the investigative team. We describe, in a general sense, the appropriate use of a piglet model for neurodevelopmental study.
    Keywords anesthesia ; animal models ; apoptosis ; catheters ; children ; clinical trials ; humans ; monitoring ; neonates ; neurons ; neurophysiology ; neurotoxicity ; piglets ; surgery
    Language English
    Dates of publication 2017-0611
    Size p. e55193.
    Publishing place Journal of Visualized Experiments
    Document type Article
    ZDB-ID 2259946-0
    ISSN 1940-087X
    ISSN 1940-087X
    DOI 10.3791/55193
    Database NAL-Catalogue (AGRICOLA)

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  4. Article: A novel, clinically relevant use of a piglet model to study the effects of anesthetics on the developing brain.

    Whitaker, Emmett E / Bissonnette, Bruno / Miller, Andrew D / Koppert, Tanner L / Tobias, Joseph D / Pierson, Christopher R / Christofi, Fievos L

    Clinical and translational medicine

    2016  Volume 5, Issue 1, Page(s) 2

    Abstract: Background: Anesthesia-induced neurotoxicity research in the developing brain must rely upon an unimpeachable animal model and a standardized treatment approach. In this manner, identification of mechanisms of action may be undertaken. The goal of this ... ...

    Abstract Background: Anesthesia-induced neurotoxicity research in the developing brain must rely upon an unimpeachable animal model and a standardized treatment approach. In this manner, identification of mechanisms of action may be undertaken. The goal of this study was to develop a novel, clinically relevant, translational way to use a piglet model to investigate anesthesia effects on the developing brain.
    Methods: 29 newborn piglets were assigned to either: (1) control (no intervention, n = 10); (2) lipopolysaccharide (LPS; positive inflammatory control, n = 9); or (3) isoflurane anesthesia (n = 10). Positive inflammatory control animals were given 100 mcg/kg LPS from Escherichia coli intraperitoneally (IP) on the same day as those receiving isoflurane. Isoflurane was administered for 3 h while care was taken to ensure human perioperative conditions. To establish a clinical scenario, each animal was intubated and monitored with pulse oximetry, invasive and non-invasive blood pressure, electrocardiogram, temperature, end-tidal CO2, anesthetic concentration, and iSTAT blood analysis. All animals were sacrificed after 48 h using transcardiac perfusion of ice-cold, heparinized phosphate buffered saline (PBS) followed by 4 % paraformaldehyde (PFA). Brains were collected and histopathological analysis focused on the entorhinal cortex looking for degenerative changes due to its critical role in learning and memory. Reliable identification of entorhinal cortex was achieved by using colored ink on the surface of the brains, which was then cross-referenced with microscopic anatomy. Hematoxylin & eosin-stained high-power fields was used to quantify cells. ImageJ™ (National Institutes of Health, Bethesda, MD, USA) was used to count absolute number of progenitor glial cells (PGC) and number of PGCs per cluster. Immunohistochemistry was also utilized to ensure positive identification of cellular structures.
    Results: Histopathological sections of 28 brains were analyzed. One animal in the LPS group died shortly after administration, presumably from inadvertent intravascular injection. There was an acute basal ganglia ischemic infarct in one isoflurane-treated animal. A large number of small, round nucleated cells were seen throughout layer II of the entorhinal cortex in all animals. These cells were identified as PGCs using immunohistochemistry and light microscopy. Although there was no difference in the absolute number of PGCs between the groups, animals given isoflurane or LPS demonstrated a significant increase in cells forming 'clusters' in the entorhinal cortex. An apparent change in the pattern of doublecortin labeling also suggests changes in neuronal precursors and undifferentiated neurons.
    Conclusions: This study represents the first novel use of a clinically relevant neonatal piglet model to study anesthesia effects on the developing brain. LPS induces neuroinflammation, and this is a potential mechanism for LPS and perhaps isoflurane in causing a change in progenitor cell distribution. We postulate that the isoflurane-induced change in glial progenitor cell distribution could have important implications for cell differentiation, maturation and neural circuit behavior in the rapidly developing brain.
    Language English
    Publishing date 2016-01-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2697013-2
    ISSN 2001-1326
    ISSN 2001-1326
    DOI 10.1186/s40169-015-0079-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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