McDermott Mary M, Dayanidhi Sudarshan, Kosmac Kate, Saini Sunil, Slysz Joshua, Leeuwenburgh Christiaan, Hartnell Lisa, Sufit Robert, Ferrucci Luigi
Department of Medicine and Preventive Medicine (M.M.M., J.S.), Northwestern University Feinberg School of Medicine.
Shirley Ryan Ability Laboratory (S.D.), Northwestern University Feinberg School of Medicine.
Circ Res. 2021 Jun 11;128(12):1851-1867. doi: 10.1161/CIRCRESAHA.121.318242. Epub 2021 Jun 10.
Walking exercise is the most effective noninvasive therapy that improves walking ability in peripheral artery disease (PAD). Biologic mechanisms by which exercise improves walking in PAD are unclear. This review summarizes evidence regarding effects of walking exercise on lower extremity skeletal muscle in PAD. In older people without PAD, aerobic exercise improves mitochondrial activity, muscle mass, capillary density, and insulin sensitivity in skeletal muscle. However, walking exercise increases lower extremity ischemia in people with PAD, and therefore, mechanisms by which this exercise improves walking may differ between people with and without PAD. Compared with people without PAD, gastrocnemius muscle in people with PAD has greater mitochondrial impairment, increased reactive oxygen species, and increased fibrosis. In multiple small trials, walking exercise therapy did not consistently improve mitochondrial activity in people with PAD. In one 12-week randomized trial of people with PAD randomized to supervised exercise or control, supervised treadmill exercise increased treadmill walking time from 9.3 to 15.1 minutes, but simultaneously increased the proportion of angular muscle fibers, consistent with muscle denervation (from 7.6% to 15.6%), while angular myofibers did not change in the control group (from 9.1% to 9.1%). These findings suggest an adaptive response to exercise in PAD that includes denervation and reinnervation, an adaptive process observed in skeletal muscle of people without PAD during aging. Small studies have not shown significant effects of exercise on increased capillary density in lower extremity skeletal muscle of participants with PAD, and there are no data showing that exercise improves microcirculatory delivery of oxygen and nutrients in patients with PAD. However, the effects of supervised exercise on increased plasma nitrite abundance after a treadmill walking test in people with PAD may be associated with improved lower extremity skeletal muscle perfusion and may contribute to improved walking performance in response to exercise in people with PAD. Randomized trials with serial, comprehensive measures of muscle biology, and physiology are needed to clarify mechanisms by which walking exercise interventions improve mobility in PAD.
步行锻炼是改善外周动脉疾病（PAD）患者步行能力最有效的非侵入性治疗方法。运动改善PAD患者步行能力的生物学机制尚不清楚。本综述总结了关于步行锻炼对PAD患者下肢骨骼肌影响的证据。在无PAD的老年人中，有氧运动可改善骨骼肌的线粒体活性、肌肉质量、毛细血管密度和胰岛素敏感性。然而，步行锻炼会增加PAD患者的下肢缺血，因此，这种锻炼改善步行的机制在有和无PAD的人群中可能有所不同。与无PAD的人相比，PAD患者的腓肠肌线粒体损伤更严重，活性氧增加，纤维化增加。在多项小型试验中，步行锻炼疗法并未持续改善PAD患者的线粒体活性。在一项针对PAD患者的为期12周的随机试验中，将患者随机分为接受监督运动组或对照组，监督下的跑步机运动使跑步机步行时间从9.3分钟增加到15.1分钟，但同时增加了角形肌纤维的比例，这与肌肉去神经支配一致（从7.6%增加到15.6%），而对照组的角形肌纤维比例没有变化（从9.1%到9.1%）。这些发现表明，PAD患者对运动的适应性反应包括去神经支配和再支配，这是在无PAD的人衰老过程中骨骼肌观察到的一种适应性过程。小型研究未显示运动对PAD参与者下肢骨骼肌毛细血管密度增加有显著影响，也没有数据表明运动能改善PAD患者的微循环氧和营养物质输送。然而，在PAD患者中，监督运动对跑步机步行试验后血浆亚硝酸盐丰度增加的影响可能与改善下肢骨骼肌灌注有关，可能有助于改善PAD患者运动后的步行表现。需要进行具有肌肉生物学和生理学系列综合测量的随机试验，以阐明步行锻炼干预改善PAD患者活动能力的机制。
