Expression of Inducible Nitric Oxide Synthase in Conduits Used in Patients with Diabetes Mellitus Undergoing Coronary Revascularization

Abstract

Expression of inducible nitric oxide synthase (iNOS) is a marker of vascular inflammation which can result in thrombosis and atherosclerosis. This study was undertaken to examine the difference in iNOS expression in the internal mammary artery (IMA) and saphenous veins (SVs) of patients with diabetes mellitus undergoing coronary artery bypass graft (CABG) surgery using both qualitative and quantitative methodology. Segments of IMA and SV harvested in 100 diabetic patients with diabetes mellitus undergoing CABG surgery were fixed in formalin and immunostained to detect the presence of iNOS. Sections were graded using a qualitative score (0 = absence of iNOS expression to 3 = extensive expression of iNOS) and a quantitative computer-aided image analysis (area of staining/area of endothelium). Linear regression analyses were performed to assess the association of the degree of iNOS expression in both the IMA and SV with the type of diabetes control (insulin, oral, diet), and the serum levels of HbAlc, glucose, free fatty acids (ffa), C-reactive protein (CRP), and low-density liproprotein (LDL) at the time of conduit harvest. The degree of iNOS expression was significantly lower in the IMA compared to the SV by both qualitative (0.88 +/- 0.74 SD IMA vs. 1.38 +/- 0.68 SV; p < 0.0001) and quantitative (11.76 +/- 3.34% IMA vs. 17.10 +/- 2.54% SV; p = 0.01) methods. The Spearman rank correlation analysis showed a highly statistically significant association between the two methodologies (p < 0.0001). There was no correlation between iNOS expression in either the IMA or SV and the type of diabetes control, or levels of HA1c, glucose, ffa, and CRP. However, there was a significant (p = 0.04) correlation between LDL and iNOS expression in the SV graft, but not the IMA. iNOS expression is significantly decreased in the IMA compared to the SV in patients with diabetes mellitus undergoing CABG surgery. The degree of iNOS expression is unrelated to the level of glycemic control at the time of conduit harvest, but is associated with serum LDL levels in the SV, but not in the IMA grafts.