Simvastatin attenuates leucocyte-endothelial interactions after coronary revascularisation with cardiopulmonary bypass.
OBJECTIVE
To investigate the effects of preoperative simvastatin treatment on leucocyte-endothelial interactions following coronary artery bypass surgery with cardiopulmonary bypass.


METHODS
Double blind crossover study. Experiments on polymorphonuclear cells (neutrophils) were done at the end of cardiopulmonary bypass and one hour postoperatively. Endothelial P-selectin expression and neutrophil/endothelial adhesion were evaluated under either normoxic or hypoxic conditions.


METHODS
University hospital (tertiary referral centre).


METHODS
Three groups of patients undergoing coronary bypass surgery: 20 patients taking simvastatin for cholesterol control, 16 patients not responsive to simvastatin, and 20 controls.


METHODS
Expression of neutrophil CD11b and endothelial P-selectin; adhesion of neutrophils to endothelium.


RESULTS
Cardiopulmonary bypass resulted in a significant increase in neutrophil CD11b expression in all groups. Similarly, the exposure of saphenous vein to hypoxia/reoxygenation induced an augmentation of endothelial P-selectin. However, both neutrophil CD11b expression and endothelial P-selectin exocytosis were less in the simvastatin groups than in the controls. Cardiopulmonary bypass and controlled hypoxia/reoxygenation stimulated neutrophil/endothelial adhesion, but the number of adhering cells was less in the simvastatin groups than in the controls, irrespective of the cholesterol concentration. Treatment of endothelial cells with L-NAME completely reversed the effects of simvastatin.


CONCLUSIONS
Pretreatment with simvastatin reduces neutrophil adhesion to the venous endothelium in patients undergoing coronary surgery, irrespective of its efficacy at lowering cholesterol concentration.
Chello
M
M
Interdisciplinary Centre for Biomedical Research (CIR), Department of Cardiovascular Sciences, University Campus Bio-Medico di Roma, Rome, Italy. m.chello@unicampus.it
Mastroroberto
P
P
Patti
G
G
D'Ambrosio
A
A
Morichetti
M Cortez
MC
Di Sciascio
G
G
Covino
E
E
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D002315:Cardiopulmonary Bypass / Q000379:methods*; D002448:Cell Adhesion; D001026:Coronary Artery Bypass / Q000379:methods; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009204:Myocardial Revascularization / Q000379:methods*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019007:P-Selectin / Q000378:metabolism; D011300:Preoperative Care; D012501:Saphenous Vein / Q000166:cytology / Q000378:metabolism; D019821:Simvastatin / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D015703:Antigens, CD; D019007:P-Selectin; D009569:Nitric Oxide; D019821:Simvastatin