Abstract 8892: Manganese Deficiency May Play a Role in Coronary Spasm, and Selenium Deficiency May Induce Cardiac Dysfunction Through the Microcirculatory Disturbance

Abstract

Background: Although manganese, zinc and copper are essential cofactors for superoxide dismutase (SOD) activation, and selenium is an essential cofactor required for activation of glutathione peroxidase (GSHPx), their roles in cardiac diseases remain unclear. We therefore investigated the relationship between levels of these trace elements and cardiac diseases using sera from patients with vasospastic angina(VSA), DCM and AMI. Methods: We compared serum concentrations of 19 elements (Li, B, Al, Ti, V, Cr, Mn, Co, Ni, As, Se, Sr, Mo, Cd, Sn, Sb, Ba, Pt and Pb) by high resolution inductively coupled plasma (ICP) mass spectrometry and of 6 other elements (Ca, Mg, P, Fe, Cu and Zn) by ICP atomic emission spectroscopy, among patients with VSA(n =12), DCM(n=41), AMI(n=18) and control subjects with normal cardiac function(n=29). We also determined serum GSHPx and free radical-generating activities and measured perivascular fibrosis ratio (PVFR) in histological preparations of autopsied hearts in DCM patients. Results: Compared to the control subjects, manganese concentrations were lower in VSA patients (0.60±0.12 vs. 0.40±0.14 ng/ml, p<0.001), while selenium and manganese concentrations were markedly lower in DCM patients (146.0±23.3 vs. 95.1±21.5 ng/ml, p<0.00001 ; 0.60±0.12 vs. 0.37±0.16 ng/ml, p<0.0001, respectively). A significant correlation was found between serum selenium concentrations and left ventricular ejection fraction (p=0.0012). The GSHPx activity was significantly lower in DCM patients than in the control subjects (221±34 vs. 328±44 μ mol/min/L, p<0.001). Furthermore, the DCM patients enhanced radical generation in the serum, and the PVFR was also increased in this group(p<0.001). Conclusions: The present study indicates that manganese deficiency may play a significant role in coronary spasm via reduction in SOD activity, resulting in increased superoxide levels which in turn inactivate NO, leading to coronary spasm. The study also suggests the possibility that selenium deficiency may play an important role in cardiac dysfunction via reduction in GSHPx activity; the resultant increase in oxidative stress induces microcirculatory disturbance, which in turn induces cardiac dysfunction.