Nitecapone reduces cardiac neutrophil accumulation in clinical open heart surgery.
BACKGROUND
To study the effect of nitecapone, a novel antioxidant, on cardiac neutrophil activation during cardiopulmonary bypass in patients.


METHODS
In a double-blind, placebo controlled trial, 30 male patients undergoing coronary artery bypass grafting were randomly assigned to control (crystalloid cardioplegia, n = 15) and nitecapone groups (cardioplegia supplemented with nitecapone, n = 15). Leukocyte differential counts, neutrophil and monocyte CD11b and L-selectin expressions and neutrophil hydrogen peroxide production were measured in blood samples parallelly obtained from the coronary sinus and aorta before cardiopulmonary bypass and at 1, 5, and 10 min after aortic declamping. Myocardial myeloperoxidase activity was analyzed in biopsies taken at 1, 5, and 10 min after declamping.


RESULTS
Transcoronary neutrophil difference (i.e., aorta--sinus coronarius) at 1 min after aortic declamping was significantly lower in nitecapone-treated patients (0.41 [-0.42-0.98] x 10(9) cells/l) than in controls (0.68 [-0.28-2.47] x 10(9) cells/l; P = 0.032). At 5 min after aortic declamping, significant transcoronary reduction of neutrophil hydrogen peroxide production and CD11b expression were observed in controls but not in nitecapone patients. At 24 h postoperatively, left ventricular stroke volume was better in nitecapone-treated patients (94 [51-118] ml) than controls (66 [40-104] ml; P= 0.018). Data are median [range].


CONCLUSIONS
Nitecapone added to cardioplegia solution reduces cardiac neutrophil accumulation and transcoronary neutrophil activation during clinical cardiopulmonary bypass. Reflected by better left ventricular stroke volume, nitecapone treatment may be an additional way of reducing the deleterious effects of neutrophil activation during cardiopulmonary bypass.
Pesonen
E J
EJ
Department of Bacteriology and Immunology, Hospital for Children and Adolescents, University of Helsinki, Finland. epesonen@helsinki.fi
Vento
A E
AE
Rämo
J
J
Vuorte
J
J
Jansson
S E
SE
Repo
H
H
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology*; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D019041:L-Selectin / Q000032:analysis; D007958:Leukocyte Count / Q000187:drug effects; D016177:Macrophage-1 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010422:Pentanones / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism
D000975:Antioxidants; D002396:Catechols; D016177:Macrophage-1 Antigen; D010422:Pentanones; D019041:L-Selectin; C057364:nitecapone; D006861:Hydrogen Peroxide; D009195:Peroxidase