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Regulation of Coronary Artery Flow during Normothermic Ex Situ Heart Perfusion

  • Author / Creator
    Qi, Xiao
  • The overall goal of this study is to improve the protocols for Ex Situ heart perfusion (ESHP) to better preserve the function and viability of donated hearts. ESHP has emerged as a new method of donor heart preservation. Unlike the standard cold storage technique, in ESHP, the heart is perfused with oxygenated, nutrient-rich solutions with warm blood during preservation, hence preventing ischemia. As a preservation method, there are solid theoretical advantages to storing donor heart in a physiological, functioning state: the organ can be resuscitated from ischemia or other acute injury. Unlike the cold storage method to decrease the metabolism, ESHP preserves the heart at normal temperature to maintain the metabolism in the myocardium. In addition, donor heart function can be used to predict viability and preservation time could be potentially prolonged. Ideal methods for maximally preserving cardiac function and graft quality using ESHP are sought after. However, the optimal approach for graft evaluation is yet to be established. Before successfully clinical application of this strategy, the establishment of effective techniques for resuscitation of the cardiac allograft and reliable methods for evaluating its transplantability is necessary.
    During heart preservation, the coronary artery function is an important part. Myocardial perfusion is regulated by a variety of factors that influence arteriolar vasomotor tone. Many researchers indicate that there was endothelial damage during ESHP. Our preliminary results showed that there was a loss of coronary artery autoregulation. The mechanisms responsible for the loss of coronary regulation during ESHP are not understood but may be related to the metabolism alteration in the myocardium or oxidative stress state of endothelium appearing during ESHP. Such change will exert its effect on the endothelium and affect the vasoactive function of the coronary artery. We aim to mitigate such functional loss and protect the coronary artery during ESHP. Also, we plan to use some additives such as oxygen-derived free radical scavengers to protect coronary artery function.
    Our preliminary data suggest that regulation of coronary artery function is disturbed during ESHP, leading to apparent excessive coronary blood flow over time. This observation contrasts with a gradual reduction in myocardial function over time, suggesting a loss of coronary regulation during ESHP. The mechanisms responsible for the loss of coronary regulation during ESHP may be related to the metabolism alteration in the myocardium or oxidative stress state of endothelium appearing during ESHP. Several other factors may also be involved in the loss of coronary regulation during ESHP, such as endothelial factors, oxygen carriers, and vasoactive mediators. We hypothesize that the change of multiple factors during ESHP would affect the endothelium and affect the vasoactive function of the coronary artery. The change of multiple elements in the regulation of coronary blood flow will be studied during the isolated working heart perfusion model.
    Understanding the physiological and pathophysiological factors that modulate coronary blood flow provides the basis for the judicious use of ESHP in providing ideal cardiac graft quality. We aim to investigate the mechanism underlying the loss of coronary autoregulation and find ways to protect coronary artery function.

  • Subjects / Keywords
  • Graduation date
    Spring 2022
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/r3-1se4-d648
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.