Morphology, metabolism, microcirculation, and strength of skeletal muscles in cancer-related cachexia

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Abstract
Cancer-related cachexia is an obscure syndrome leading to muscle wasting, reduced physical fitness and quality of life. The aim of this study was to assess morphology, metabolism, and microcirculation in skeletal muscles of patients with cancer-related cachexia and to compare these data with matched healthy volunteers. In 19 patients with cancer-induced cachexia and 19 age-, gender-, and body-height-matched healthy volunteers body composition and aerobic capacity (VO(2max)) were analyzed. Skeletal muscle fiber size and capillarization were evaluated in biopsies of the vastus lateralis muscle. The cross-sectional area (CSA) of the quadriceps femoris muscle was measured by magnetic resonance imaging as well as its isokinetic and isometric force. The energy and lipid metabolism of the vastus lateralis muscle was quantified by (31)P and (1)H spectroscopy and parameters of its microcirculation by contrast-enhanced ultrasonography (CEUS). Morphologic parameters were about 30% lower in cachexia than in volunteers (body mass index: 20 +/- 3 vs. 27 +/- 4 kg m(-2), CSA: 45 +/- 13 vs. 67 +/- 14 cm(2), total fiber size: 2854 +/- 1112 vs. 4181 +/- 1461 microm(2)). VO(2max) was reduced in cachexia (23 +/- 9 vs. 32 +/- 7 ml min(-1) kg(-1), p=0.03), whereas histologically determined capillary density and microcirculation in vivo were not different. Both concentrations of muscular energy metabolites, pH, and trimethyl-ammonium-containing compounds were comparable in both groups. Absolute strength of quadriceps muscle was reduced in cachexia (isometric: 107 +/- 40 vs. 160 +/- 40 Nm, isokinetic: 101 +/- 46 vs. 167 +/- 50 Nm; p=0.03), but identical when normalized on CSA (isometric: 2.4 +/- 0.5 vs. 2.4 +/- 0.4 Nm cm(-2), isokinetic: 2.2 +/- 0.4 vs. 2.5 +/- 0.5 Nm cm(-2)). Cancer-related cachexia is associated with a loss of muscle volume but not of functionality, which can be a rationale for muscle training.