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Hypoxic Pulmonary Vasoconstriction Is a More Accurate Parameter Than P/F Ratio to Measure Lung Function on Ex-Vivo Lung Perfusion

  • Author / Creator
    Alzamil, Almothana F
  • Hypoxic Pulmonary Vasoconstriction is a more accurate parameter than P/F ratio to measure lung function on Ex-Vivo Lung Perfusion Abstract Background: Rates of thoracic donor organ utilization remains very low at 15-25% internationally. Development of normothermic Ex-Vivo Lung Perfusion (EVLP) has shown to increase rates of donor lung utilization. Adoption of EVLP to routine clinical practice will require more sensitive physiological parameters of lung function on EVLP. Currently, P/F ratio has been used as the most reliable parameter of lung function on EVLP. Our data suggests a change in the lungs response to hypoxic pulmonary vasoconstriction (HPV) is a more sensitive parameter to detect early lung dysfunction on EVLP. Methods: Our novel EVLP platform as an apparatus for large animal model and human pre-clinical/clinical investigation, has two centrifugal flow pumps (instead of one) and it is equipped with a computer-controlled feedback system that provides real-time control of PA and LA pressures/flows as well as monitoring/recording the ventilator parameters (such as peak/plateau pressures, PEEP) and lung perfusion data (i.e. PVR) with 10sec intervals. We challenged the lungs with hypoxia serially during the EVLP run by ventilating the lungs with 100% N2 to observe the response of hypoxic pulmonary vasoconstriction (HPV). Results: We performed EVLP on 10 domestic pigs (40-45kg) for 12 hours each. We found our device provided excellent lung function while on EVLP up to 12 hours, with the P/F ratio remaining >400 mmHg throughout. EVLP was maintained at 75% cardiac output (2.2-2.4 L/min), where PA pressure and LA pressure are controlled constant by the device software at 8 mmHg and 2 mmHg, respectively. Lung compliance remained stable up to 12 hours without significant changes to peak/mean airway pressures, and PVR. When lungs were challenged with hypoxia, there was a serial blunting in HPV response over the course of 12 hours with a decreased rise in PVR when challenged with hypoxia (p<0.05). Conclusions: As experience is gained with EVLP, appreciation of the most sensitive parameters for donor lung function is critical to allow for extended EVLP runs, and to assess therapeutic interventions. The conventional use of P/F ratios may not reflect sub-clinical lung dysfunction, while response to HPV may be a more sensitive physiologic measurement of lung function. Acronyms: EVLP: Ex-vivo lung perfusion. P/F ratio: Pulmonary venous PO2/Fraction of inhaled oxygen. HPV: Hypoxic Pulmonary Vasoconstriction

  • Subjects / Keywords
  • Graduation date
    2017-11
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3V40KC8T
  • 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.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Master's
  • Department
    • Department of Surgery
  • Specialization
    • Experimental Surgery
  • Supervisor / co-supervisor and their department(s)
    • Dr. Nagendran, Jayan (Department of Surgery)
  • Examining committee members and their departments
    • Churchill, Tom (Department of Surgery)
    • Freed, Darren (Depatment of Surgery)
    • Sutendra, Gopinath (Department of Medicine)
    • Nagendran, Jayan