Ultrastructural analysis of skeletal muscle: Microvascular dimensions and basement membrane thickness in chronic heart failure

Chronic heart failure (CHF) is characterized by increased systemic vascular resistance and diminished blood flow to exercising skeletal muscle. The pathogenesis of the increased resistance is not known, and may be due to muscle atrophy, functional abnormalities of resistance vessels or to structural changes in the microcirculation such as endothelial cell swelling. We have compared the ultrastructure of the microvasculature in needle biopsies of the quadriceps muscle from seven control subjects with normal left ventricular function to 10 patients with moderate or severe heart failure, optimally treated and without evidence of fluid overload. Samples were processed for ultrathin sectioning using ruthenium red as a specific basement membrane (BM) stain. Electron micrographs were taken of 10 transversely cut capillaries from each specimen. The total cross-sectional area of the vessels and the area of the endothelium was determined, and the short axis diameter was measured as an index of vessel diameter. The BM thickness was calculated from the mean of six readings around the periphery of the vessel. The short axis diameter in the two groups was not significantly different (controls 3.37±0.21 μm, CHF 3.56±0.37μm, mean± 1SD). No difference in total cross-sectional area (controls 11.64 ± 1.86μm², CHF 13.56± 2.78μm²) or area of the endothelium (controls 4. 90 ± 1.18μm², CHF6.00 ± 1.58 μm²) was observed. The thickness of the BM was marginally increased in subjects with CHF when compared to control subjects (0.31 ± 0.077 μm vs 0.246 ± 0.047 μm, P=0.05). The three patients with ischaemic cardiomyopathy displayed abnormal morphology and localized thickening of the basement membrane. In subjects with severe treated CHF, the increased resistance in skeletal muscle vasculature is not due to ultrastructural changes in the capillaries or to endothelial cell swelling.