Abstract 302: Presence of Oxidized Low-Density Lipoprotein in the Left Ventricular Blood of Subjects with Cardiovascular Diseases

Abstract

Hypothesis: Oxidized low density lipoprotein (Ox-LDL) has properties that profoundly affect cardiovascular function. We hypothesized that Ox-LDL is likely to be formed in the left ventricular blood (LVB) when the heart is subjected to ischemic conditions and the ejection fraction (EF) is low. We speculated whether “stagnation” of LDL in the LV could result in increased formation of Ox-LDL. Objective: We studied whether there is an increased level of Ox-LDL in the LVB as opposed to peripheral blood (PB), and whether its presence correlated with the EF. Also we examined whether a higher level of Ox-LDL negatively correlated with the activity of paraoxonase 1 (PON 1). Methods: Following the Institutional Review Board (IRB) approval, 62 HF patients were enrolled in the study. All patients underwent pre-operative transthoracic echocardiographic assessment of ventricular function. Left ventricular ejection fractions were determined using the Simpsons bi-plane technique. 2ml of LVB and 5ml of PB samples were taken before coronary artery bypass surgery, or a surgery with replacement of mitral, aortic or tricuspid valve. Blood level of Ox-LDL was determined by ELISA (Mercodia), and PON 1 activity was determined by the rate of conversion of its substrate p-nitrophenyl acetate into p-nitrophenol. Results: The result showed significant increase in Ox-LDL in LVB as compared to PB (p=0.032) in HF subjects even when EF was near normal. There was no significant increase in subjects with lower EF. In contrast, Ox-LDL levels increased in the PB of subjects with lower EF and reached those of LVB. We also noticed that there was a statistically significant negative correlation between EF and Ox-LDL levels in both LVB and PB (p < 0.05). The activity of PON1, an antioxidant enzyme that protects LDL from oxidation showed decreased levels both in LV blood as well as in PB with decreased EF. It was observed that there was a statistically significant difference in PON1 levels between LV and PB of subjects having EF>60% (p = 0.03). Conclusions: In conclusion the results suggest that there might be oxidative stress associated with LVB even when the EF is not compromised. In contrast, the increase in PB Ox-LDL with poor EF might suggest that the low blood flow to peripheral tissues and end organs also might contribute to increased oxidative stress. The results also might suggest that persistent oxidative stress could have affected the clearance mechanisms of Ox-LDL.