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


Other title
Nitric Oxide
Endothelium-Derived Hyperpolarizing Factor
Type of item
Degree grantor
University of Alberta
Author or creator
Gragasin, Ferrante S.
Supervisor and department
Davidge, Sandra (dept. of Physiology)
Examining committee member and department
Thebaud, Bernard (dept. of Physiology)
Finegan, Barry (dept. of Anesthesiology and Pain Medicine)
Kassiri, Zamineh (dept. of Physiology)
Ansley, David (dept. of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia)
Leslie, Elaine (chair of exam, dept. of Physiology)
Department of Physiology

Date accepted
Graduation date
Doctor of Philosophy
Degree level
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.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Gragasin FS, Bourque SL, Davidge ST. Vascular aging and hemodynamic stability in the intraoperative period. Front Physiol. 2012;3:74Gragasin FS, Davidge ST. The Effects of Propofol on Vascular Function in Mesenteric Arteries of the Aging Rat. Am J Physiol Heart Circ Physiol. 2009 Jul;297(1):H466-74.Gragasin FS, Bourque SL, Davidge ST. Propofol Increases Vascular Relaxation in Aging Rats Chronically Treated With the Angiotensin-Converting Enzyme Inhibitor Captopril. Anesth Analg. 2013 Apr; 116(4):775-83.Gragasin FS, Davidge ST, and Tsui BC. The potential use of intralipid to minimize propofol's cardiovascular effects. Can J Anaesth. 2009 Feb;56(2):170-1.

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