Lipofuscin in Cardiac Hypertrophy

Abstract

Summary Quantitative investigations on the lipofuscin content in human hearts from various weight classes should allow us to conclude whether or not a correlation exists between pigment content and the degree of cardiac hypertrophy. The investigations were performed on 7 μ thick tissue sections from 12 autopsied hearts, and included microscopic determinations of nuclear size, fiber width, and pigment content. Nuclear volume was calculated according to the formula of a simple circular cylinder. Lipofuscin granules, stored at the nuclear poles in the form of two circular cones, were counted directly in an optical plane and their total quantity in single heart muscle cells was calculated on the basis of nuclear volume. In addition, the chemical composition of lipofuscin was investigated by means of absorption measurements on 3 μ thick sections from the myocardium of five hearts. This led to the following results : 1. A correlation between granule content and width of heart muscle fibers was established. The pigment granule count increases with increasing fiber width and reaches a maximum of 43 granules per measuring plane among 17 μ wide fibers, in which 100-114 granules per fiber are present. No further increase in the pigment content was found as the fiber width increased still further. 2. Pigment granule count per measuring plane increased with increasing nuclear size. Maximal pigment accumulation was found among 17 μ thick heart muscle cells with nuclei 250 μ3 in size. 3. Lipofuscin content increases with increasing heart weight up to 500 g and decreases with further cardiac hypertrophy. 4. Cytophotometric measurements of intracellular and isolated lipofuscin resulted in a clear absorption peak at 280 nm, evidence for the presence of tyrosine and tryptophan, and a shoulder in the 300–400 nm region, related to the presence of conjugated fatty acids. These results indicate that lipofuscin content in heart muscle is correlated to the degree of cardiac hypertrophy (fiber width, nuclear size). Lipofuscin content, which probably represents a degradation product of cellular components (membranes, mitochondria), is related to an increased functional output of the hypertrophied heart.