Effects of atorvastatin on arterial endothelial function in coronary bypass surgery.
OBJECTIVE
Endothelial dysfunction represents a critical early component of organ injury following cardiopulmonary bypass. Recent studies demonstrate that the treatment with atorvastatin is associated with a significant improvement of endothelial function independently of its efficacy on cholesterol levels. Therefore, we investigated the effects of preoperative atorvastatin treatment on endothelium function after coronary surgery.


METHODS
Forty patients undergoing coronary surgery were randomized to treatment with atorvastatin (20 mg/die; N=20) or placebo (N=20) 3 weeks before surgery. Twenty normal patients served as control group. The flow-mediated dilations (FMD) of the brachial artery after both reactive hyperemia (endothelium dependent) and nitroglycerin administration (endothelium independent) were evaluated at baseline, at 48 h, and 5 days postoperatively.


RESULTS
At baseline, the endothelium-dependent FMD was significantly attenuated in coronary versus normal patients (normal 10.3+/-1.8% vs coronary 4.1+/-1.6%, p<0.01). At 48 h postoperatively all patients exhibited a reduced FMD compared with baseline values: the endothelium-dependent dilatation showed a drop of 60.1+15% in the patients of the placebo group compared with 45.8+16.6% (p<0.05) those in the atorvastatin group. At the univariate analysis, no significant correlation was found between serum levels of either total cholesterol or HDL cholesterol and FMD. The nitroglycerin-induced dilation was not significantly influenced by extracorporeal circulation as well as by atorvastatin treatment.


CONCLUSIONS
The endothelial dysfunction following cardiopulmonary bypass is improved by the treatment with atorvastatin, by a mechanism unrelated to the drug efficacy of controlling serum cholesterol levels.
Chello
Massimo
M
Interdisciplinary Center for Biomedical Research (CIR), Department of Cardiovascular Sciences, Unit of Cardiac Surgery, University Campus Bio Medico di Roma, Via E. Longoni 83, Rome 00155, Italy. m.chello@unicampus.it
Goffredo
Costanza
C
Patti
Giuseppe
G
Candura
Dario
D
Melfi
Rosetta
R
Mastrobuoni
Stefano
S
Di Sciascio
Germano
G
Covino
Elvio
E
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000069059:Atorvastatin; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006940:Hyperemia / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin; D011184:Postoperative Period; D011758:Pyrroles / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014665:Vasodilator Agents; D002784:Cholesterol; D000069059:Atorvastatin; D005996:Nitroglycerin