Propofol attenuates lung endothelial injury induced by ischemia-reperfusion and oxidative stress.
Lung dysfunction after cardiopulmonary bypass and lung transplantation results from oxidant-mediated cellular damage. Previously, we observed the shedding of angiotensin-converting enzyme (ACE) from the endothelial cell surface to be a more sensitive and earlier marker of oxidative lung endothelial injury than lung wet-to-dry weight ratio. The aim of this study was to evaluate the potential of the anesthetic propofol, which has antioxidant properties, to prevent oxidative lung injury by measuring ACE shedding. ACE release from isolated perfused rat lungs increased significantly after ischemia-reperfusion (I/R). Propofol significantly decreased I/R-induced ACE release by 23.4% (P < 0.05). Perfusion with 0.75 mM H(2)O(2) also caused ACE release from the lung microvasculature, which was similarly attenuated by propofol. The protective effect of propofol on H(2)O(2)-induced ACE shedding was confirmed in vitro using Chinese Hamster Ovary cells overexpressing human ACE. Thus, propofol can attenuate oxidative injury of the pulmonary endothelium as detected by ACE shedding in I/R and H(2)O(2) models of acute lung injury.
Balyasnikova
Irina V
IV
Departments of Anesthesiology and Pharmacology, University of Illinois at Chicago, Chicago, Illinois.
Visintine
David J
DJ
Gunnerson
Helena B
HB
Paisansathan
Chanannait
C
Baughman
Verna L
VL
Minshall
Richard D
RD
Danilov
Sergei M
SM
D018686:Anesthetics, Intravenous / Q000627:therapeutic use*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004727:Endothelium / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006861:Hydrogen Peroxide / Q000633:toxicity; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010477:Perfusion; D015742:Propofol / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*
D018686:Anesthetics, Intravenous; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D007703:Peptidyl-Dipeptidase A; D015742:Propofol