Division of Pulmonary/Critical Care Medicine, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
J Appl Physiol (1985). 2012 Jan;112(1):72-8. doi: 10.1152/japplphysiol.00556.2011. Epub 2011 Oct 20.
Muscle weakness and effort intolerance are common in maintenance hemodialysis (MHD) patients. This study characterized morphometric, histochemical, and biochemical properties of limb muscle in MHD patients compared with controls (CTL) with similar age, gender, and ethnicity. Vastus lateralis muscle biopsies were obtained from 60 MHD patients, 1 day after dialysis, and from 21 CTL. Muscle fiber types and capillaries were identified immunohistochemically. Individual muscle fiber cross-sectional areas (CSA) were quantified. Individual fiber oxidative capacities were determined (microdensitometric assay) to measure succinate dehydrogenase (SDH) activity. Mean CSAs of type I, IIA, and IIX fibers were 33, 26, and 28% larger in MHD patients compared with CTL. SDH activities for type I, IIA, and IIX fibers were reduced by 29, 40, and 47%, respectively, in MHD. Capillary to fiber ratio was increased by 11% in MHD. The number of capillaries surrounding individual fiber types were also increased (type I: 9%; IIA: 10%; IIX: 23%) in MHD patients. However, capillary density (capillaries per unit muscle fiber area) was reduced by 34% in MHD patients, compared with CTL. Ultrastuctural analysis revealed swollen mitochondria with dense matrix in MHD patients. These results highlight impaired oxidative capacity and capillarity in MHD patients. This would be expected to impair energy production as well as substrate and oxygen delivery and exchange and contribute to exercise intolerance. The enlarged CSA of muscle fibers may, in part, be accounted for by edema. We speculate that these changes contribute to reduce limb strength in MHD patients by reducing specific force.
肌肉无力和运动不耐受在维持性血液透析(MHD)患者中很常见。本研究比较了具有相似年龄、性别和种族的 MHD 患者和对照组(CTL)的肢体肌肉形态计量学、组织化学和生物化学特性。在透析后 1 天,从 60 名 MHD 患者和 21 名 CTL 中获取了股外侧肌活检组织。用免疫组织化学方法鉴定肌肉纤维类型和毛细血管。定量测量单个肌纤维的横截面积(CSA)。用微密度测定法测定个体纤维的氧化能力,以测量琥珀酸脱氢酶(SDH)活性。与 CTL 相比,MHD 患者的 I 型、IIA 型和 IIX 型纤维的平均 CSA 分别大 33%、26%和 28%。SDH 活性分别降低了 29%、40%和 47%。MHD 患者的毛细血管与纤维比增加了 11%。MHD 患者围绕各类型纤维的毛细血管数量也增加(I 型:9%;IIA 型:10%;IIX 型:23%)。然而,与 CTL 相比,MHD 患者的毛细血管密度(每单位肌肉纤维面积的毛细血管数)降低了 34%。超微结构分析显示 MHD 患者的线粒体肿胀,基质致密。这些结果突出了 MHD 患者氧化能力和毛细血管受损。这预计会损害能量产生以及底物和氧气的输送和交换,并导致运动不耐受。肌肉纤维 CSA 的增大部分可能是由于水肿所致。我们推测这些变化通过降低比肌力来减少 MHD 患者的肢体力量。