HETEROGENEOUS DISTRIBUTION OF A FATTY-ACID ANALOG UPTAKE IN THE MYOCARDIUM OF AGED RATS

The aim of this study was to determine the extent and location of dama ged myocardial areas in senescent rats. The viability of myocardial ce lls was evaluated in virgin young (4 months old) and aged (29 months a id) female Wistar rats by analysing the uptake of a slowly metabolisab le radiolabelled fatty acid analogue, 15-p-iodophenyl-beta-methylpenta decanoic acid (IMPPA). The biodistribution of IMPPA was measured in va rious organs, and regional myocardial uptake was specifically assessed using quantitative autoradiography. Myocardial enzymatic activity and DNA content were also evaluated with nitro blue tetrazolium (NBT) and propidium iodide (PI) staining, respectively. In senescent rats, card iac and renal IMPPA uptake showed a significant (50%) reduction compar ed with young adult rats and the uptake was not significantly changed in the liver, spleen, lungs, and skeletal muscle. Total ventricular NB T staining and IMPPA uptake were almost homogeneous in young adult rat s, whereas they were very heterogeneous in aged rats. In the latter, a pproximately 11% of the total ventricular volume showed a significantl y decreased (by 60% or more) IMPPA uptake compared with normal values, and this reduction was greater in ventricle base than in apex. The my ocardial areas unlabelled or poorly labelled by IMPPA represented 4, 5 , 6, and 21% of the right ventricular, left ventricular epicardial, se ptal, and left ventricular endocardial volume, respectively, and were poorly stained with NBT. In some of these areas, PI staining indicated the presence of living cells unable to pick up NBT staining. In concl usion, in young adult rats, no myocardial lesions were observed using three different labelling techniques. However, important and significa nt myocardial lesioned areas were detected in senescent rats and were located preferentially in the left ventricular endocardium, as shown b y a decrease in NBT staining and IMPPA uptake. These likely correspond ed to a reduced number of cardiomyocytes and (or) a reduced aerobic su bstrate utilization, along with the development of fibrosis.