Protective effect of antioxidants on pulmonary endothelial function after cardiopulmonary bypass.
OBJECTIVE
Pulmonary endothelium-dependent vasodilation is impaired after cardiopulmonary bypass. One explanation might be the generation of reactive oxygen species during the period without flow in the pulmonary artery. The aim of the current study was to investigate if treatment with antioxidants could improve pulmonary endothelial function after cardiopulmonary bypass and influence the blood oxidative status.


METHODS
A prospective, randomized, double-blind study.


METHODS
The operating room, intensive care unit, and the biochemistry laboratory in University Hospitals.


METHODS
Patients scheduled for cardiac surgery with cardiopulmonary bypass.


METHODS
Treatment with vitamin E, vitamin C, allopurinol, and acetylcysteine (n = 12) or placebo (n = 10).


RESULTS
The pulmonary reactivity to an infusion of acetylcholine and markers of oxidative stress in blood were measured before and after cardiopulmonary bypass. Sixteen control patients received saline instead of acetylcholine. Before surgery the pulmonary vascular resistance index decreased during infusion of acetylcholine by 24% and 21% in the treatment and placebo groups. After surgery the decrease was 20% and 8%, respectively, (p = 0.422 and p = 0.026) compared with preoperative response. Pulmonary vasodilation induced by acetylcholine was better maintained in the group treated with antioxidants (p = 0.048). In the treatment group, the blood concentrations of early intermediates of lipid peroxidation were higher, but not that of the end products. Glutathione and oxidized glutathione increased after cardiopulmonary bypass in the treatment group.


CONCLUSIONS
The better maintained endothelium-dependent vasodilation after cardiopulmonary bypass in the treatment group indicated that antioxidant therapy reduced endothelial dysfunction.
Angdin
Monika
M
Department of Surgical Sciences, Karoliniska Institute, Division of Cardiothoracic Anaesthetics and Intensive Care, Karoliniska Hospital, Stockholm, Sweden. 087527848@telia.com
Settergren
Göran
G
Starkopf
Joel
J
Zilmer
Mihkel
M
Zilmer
Kersti
K
Vaage
Jarle
J
D000109:Acetylcholine / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D019803:Glutathione Disulfide / Q000097:blood; D006801:Humans; D007261:Infusions, Intra-Arterial; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000098:blood supply* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use
D000975:Antioxidants; D014665:Vasodilator Agents; D000109:Acetylcholine; D019803:Glutathione Disulfide