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Differential effect of cerivastatin and L-arginine on the vascular function of human radial and left internal thoracic arteries
Authors:Nakamura Koki  Al-Ruzzeh Sharif  Chester Adrian H  Ilsley Charles  Yacoub Magdi H  Amrani Mohamed
Affiliation:National Heart and Lung Institute, Heart Science Centre, Harefield Hospital, Harefield, Middlesex, United Kingdom.
Abstract:
BACKGROUND: There are a number of strategies to restore/preserve endothelial function. We have compared the effects of Cerivastatin (CS) to those of L-arginine (L-ARG) supplementation on the endothelial function of human arterial grafts. METHODS: During coronary artery bypass grafting, specimens of radial artery (RA) and left internal thoracic artery (LITA) were obtained. Specimens were divided into vascular rings, which were incubated with either 10(-6) mol/L CS, 10(-3) mol/L L-ARG, or vehicle (control) for 2 or 24 hours. Endothelial function was examined with acethylcholine (10(-9) to 10(-5) mol/L) following contraction by 3 x 10(-8) mol/L endothelin-1. RESULTS: Although no significant differences were observed in the RA at 2 hours, after 24 hours incubation, endothelium-dependent vasodilatation was significantly higher in CS group (68.4 +/- 5.0%; n = 6) compared to L-ARG group (49.9 +/- 5.4%; n = 7, p < 0.05) and control group (33.8 +/- 2.9%; n = 13, p < 0.0001). In addition, there was a significant increase in L-ARG group compared to control (p < 0.01). After 2 hours incubation of the LITA, CS failed to enhance endothelium-dependent vasodilatation compared to control (44.1 +/- 4.9%; n = 9, vs. 40.0 +/- 5.2%; n = 16, respectively, NS), while L-ARG increased it (64.7 +/- 4.9%; n = 7, p < 0.05 vs. CS and p < 0.01 vs. control). However, this increase disappeared at 24 hours although there was a higher trend of endothelium-dependent vasodilatation in CS group (30.3 +/- 3.7%; n = 8 in L-ARG, 56.5 +/- 8.8%; n = 9 in CS and 41.0 +/- 5.5%; n = 18 in control). CONCLUSIONS: CS preserved endothelium-dependent vasodilatation of RA greater than L-ARG. These findings suggest that the use of statins may be an effective therapeutic strategy to preserve endothelial function in the RA grafts, and could have important implications in the clinical practice.
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