The Use of Doxycycline in Asphyxiated Newborns

  • Author / Creator
    LaBossiere, Joseph R
  • Asphyxia is a significant cause of newborn morbidity and mortality. Multiorgan injury and dysfunction is a common finding, mediated in part through an increase in matrix metalloproteinase (MMP) activity. We hypothesized administration of doxycycline, a known MMP inhibitor, would improve systemic and regional hemodynamics as well as attenuate myocardial, renal and intestinal injury and dysfunction in a clinically translatable newborn swine model of hypoxia-reoxygenation. Newborn piglets were subjected to hypoxia-reoxygenation and received normal saline (control) or one of three doses of doxycycline five minutes into resuscitation. Doxycycline improved recovery of cardiac index, stroke volume index, systemic arterial pressure (SAP), systemic oxygen delivery and consumption with no effect on heart rate. Pulmonary artery pressure (PAP) and PAP/SAP were reduced, while renal artery flow index and oxygen delivery were improved. Markers of myocardial, renal and intestinal injury were attenuated with doxycycline and associated with a reduction in tissue oxidative stress and total MMP-2 activity. We conclude that in a clinically translatable newborn swine model of hypoxia-reoxygenation, early administration of doxycycline during resuscitation improves systemic and regional hemodynamics, and attenuates myocardial, renal and intestinal injury.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • 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
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Surgery
  • Specialization
    • Experimental Surgery
  • Supervisor / co-supervisor and their department(s)
    • Cheung, Po-Yin (Pharmacology/Surgery/Pediatrics)
    • Bigam, David (Surgery)
  • Examining committee members and their departments
    • Churchill, Tom (Surgery)
    • Bigam, David (Surgery)
    • Schulz, Richard (Pharmacology)
    • Cheung, Po-Yin (Pharmacology/Surgery/Pediatrics)