Anesthesia and the Aging Vasculature: Effects of Propofol on Hemodynamics and Vascular Function

  • Author / Creator
    Gragasin, Ferrante S.
  • An increasing life expectancy in Canada has resulted in increasing proportions of elderly patients requiring anesthetic care for surgical procedures. Aging is associated with cardiovascular changes resulting in increased vasoconstriction and hypertension, and medications such as angiotensin converting enzyme (ACE) inhibitors are commonly prescribed for this reason. Propofol, a commonly used general anesthetic agent, is known to cause hypotension that can be exaggerated in the elderly population. Propofol’s influence on vascular reactivity has not been investigated in the aging vasculature. Moreover, patients using ACE inhibitors in the perioperative period may exhibit refractory hypotension when given a general anesthetic. Whether propofol differentially alters vascular function in arteries exposed to chronic ACE inhibition is also not known. Therefore, this thesis focused on 1) determining if there is a difference in vasodilating ability between the young and aging vasculature when exposed to propofol, and 2) determining if chronic ACE inhibition differentially alters vasodilation in the presence of propofol in the aging vasculature. Additionally, the utility of Intralipid as a potential treatment for propofol-induced hypotension was investigated in this thesis. Previous publications suggest that multiple mediators are involved in propofol-induced vascular relaxation. Here, the focus was on nitric oxide (NO) given the age-dependent decrease in NO bioavailability and based on studies documenting the contribution of NO following propofol administration in young mesenteric arteries, the primary vascular bed studied here. The experiments presented in this thesis demonstrate enhanced bioavailability of NO in the aging vasculature in the presence of propofol. Although NO is important, the aging vasculature chronically treated with ACE inhibitors possesses an enhanced vasodilation in the presence of propofol that results from a non-NO source. Finally, Intralipid is able to reverse propofol-induced vasodilation and hypotension in aging animals, demonstrating its potential to be utilized as a hemodynamic agent following propofol use. In conclusion, the results presented in this thesis are an important contribution to understanding the effects of propofol, a widely used general anesthetic agent, on the aging vasculature. This is of particular importance given the increasing proportion of the aging population presenting for surgery and requiring the care of the Anesthesiologist.

  • Subjects / Keywords
  • Graduation date
    Spring 2014
  • Type of Item
  • Degree
    Doctor of Philosophy
  • 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
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • Leslie, Elaine (chair of exam, dept. of Physiology)
    • Kassiri, Zamineh (dept. of Physiology)
    • Thebaud, Bernard (dept. of Physiology)
    • Finegan, Barry (dept. of Anesthesiology and Pain Medicine)
    • Ansley, David (dept. of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia)