LAUSR

Altered iron status may be relevant to the pathophysiology of aging. We have assessed redox-active catalytic low molecular weight iron (LMWI), non-heme iron (NHI), heme iron (HI), and total iron (TI) in the aerobically perfused hearts of aged rabbits (AR, about 4.5years old) and young adult control rabbits (YACR, 3-4months old); myocardial lipid and protein oxidations were also assessed as oxidative stress biomarkers. The levels of LMWI and NHI, as well as of lipid and protein oxidation, were higher, while HI content was lower, in the hearts of AR than in those of YACR; TI did not differ significantly between the two groups. Together with these findings, hemodynamic dysfunction, namely heightened end-diastolic pressure (EDP) and lowered coronary flow (CF), occurred in the AR hearts. Notably, such pattern of hemodynamic dysfunction associated with myocardial oxidant damage occurred in the hearts of other YACR perfused in the presence of a cell-permeable form of iron, i.e., the iron/hydroxyquinoline complex, pointing to the involvement of catalytic iron in the aged heart damage. Moreover, as shown in other AR, heart perfusion in the presence of the iron chelator deferoxamine (0.6mM or 3.6mM) reduced the myocardial levels of LMWI, without significantly affecting those of NHI, HI, and TI; concomitantly, in AR deferoxamine lowered myocardial lipid and protein oxidation, and reduced EDP with a tendency to augment CF. Instead, deferoxamine, even at high concentration of 3.6mM, had no significant effects in the YACR. In conclusion, altered iron status with catalytic LMWI burden occurs in the aged rabbit heart, eventually resulting in iron-dependent cardiac oxidative stress and hemodynamic dysfunction.