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  • Manouchehri, Neda  (2)
  • Biology  (2)
  • 1
    In: The Journal of Physiology, Wiley, Vol. 598, No. 5 ( 2020-03), p. 929-942
    Abstract: We have developed a novel porcine model of high‐thoracic midline contusion spinal cord injury (SCI) at the T2 spinal level. We describe this model and the ensuing cardiovascular and neurohormonal responses, and demonstrate the model is efficacious for studying clinically relevant cardiovascular dysfunction post‐SCI. We demonstrate that the high‐thoracic SCI model, but not a low‐thoracic SCI model, induces persistent hypotension along with a gradual reduction in plasma noradrenaline and increases in plasma aldosterone and angiotensin II. We additionally conducted a proof‐of‐concept long‐term (12 weeks) survival study in animals with T2 contusion SCI demonstrating the potential utility of this model for not only acute experimentation but also long‐term drug studies prior to translation to the clinic.
    Type of Medium: Online Resource
    ISSN: 0022-3751 , 1469-7793
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 1475290-6
    SSG: 12
    Location Call Number Limitation Availability
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  • 2
    In: The Journal of Physiology, Wiley, Vol. 600, No. 22 ( 2022-11), p. 4779-4806
    Abstract: The assessment of left ventricular (LV) contractility in animal models is useful in various experimental paradigms, yet obtaining such measures is inherently challenging and surgically invasive. In a cross‐species study using small and large animals, we comprehensively tested the agreement and validity of multiple single‐beat surrogate metrics of LV contractility against the field‐standard metrics derived from inferior vena cava occlusion (IVCO). Fifty‐six rats, 27 minipigs and 11 conscious dogs underwent LV and arterial catheterization and were assessed for a range of single‐beat metrics of LV contractility. All single‐beat metrics were tested for the various underlying assumptions required to be considered a valid metric of cardiac contractility, including load‐independency, sensitivity to inotropic stimulation, and ability to diagnose contractile dysfunction in cardiac disease. Of all examined single‐beat metrics, only LV maximal pressure normalized to end‐diastolic volume (EDV), end‐systolic pressure normalized to EDV, and the maximal rate of rise of the LV pressure normalized to EDV showed a moderate‐to‐excellent agreement with their IVCO‐derived reference measure and met all the underlying assumptions required to be considered as a valid cardiac contractile metric in both rodents and large‐animal models. Our findings demonstrate that single‐beat metrics can be used as a valid, reliable method to quantify cardiac contractile function in basic/preclinical experiments utilizing small‐ and large‐animal models image Key points Validating and comparing indices of cardiac contractility that avoid caval occlusion would offer considerable advantages for the field of cardiovascular physiology. We comprehensively test the underlying assumptions of multiple single‐beat indices of cardiac contractility in rodents and translate these findings to pigs and conscious dogs. We show that when performing caval occlusion is unfeasible, single‐beat metrics can be utilized to accurately quantify cardiac inotropic function in basic and preclinical research employing various small and large animal species. We report that maximal left‐ventricular (LV)‐pressure normalized to end‐diastolic volume (EDV), LV end‐systolic pressure normalized to EDV and the maximal rate of rise of the LV pressure waveform normalized to EDV are the best three single‐beat metrics to measure cardiac inotropic function in both small‐ and large‐animal models.
    Type of Medium: Online Resource
    ISSN: 0022-3751 , 1469-7793
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1475290-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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