Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE7 7DN, UK.
Int J Cardiol. 2013 Oct 9;168(4):3599-608. doi: 10.1016/j.ijcard.2013.05.062. Epub 2013 Jun 3.
Cardiac hypertrophic remodelling and systolic dysfunction are common in patients with mitochondrial disease and independent predictors of morbidity and early mortality. Endurance exercise training improves symptoms and skeletal muscle function, yet cardiac adaptations are unknown.
Before and after 16-weeks of training, exercise capacity, cardiac magnetic resonance imaging and phosphorus-31 spectroscopy, disease burden, fatigue, quality of life, heart rate variability (HRV) and blood pressure variability (BPV) were assessed in 10 adult patients with m.3243A>G-related mitochondrial disease, and compared to age- and gender-matched sedentary control subjects. At baseline, patients had increased left ventricular mass index (LVMI, p<0.05) and LV mass to end-diastolic volume ratio, and decreased longitudinal shortening and myocardial phosphocreatine/adenosine triphosphate ratio (all p<0.01). Peak arterial-venous oxygen difference (p<0.05), oxygen uptake (VO2) and power were decreased in patients (both p<0.01) with no significant difference in cardiac power output. All patients remained stable and completed ≥80% sessions. With training, there were similar proportional increases in peak VO2, anaerobic threshold and work capacity in patients and controls. LVMI increased in both groups (p<0.01), with no significant effect on myocardial function or bioenergetics. Pre- and post-exercise training, HRV and BPV demonstrated increased low frequency and decreased high frequency components in patients compared to controls (all p<0.05).
Patients with mitochondrial disease and controls achieved similar proportional benefits of exercise training, without evidence of disease progression, or deleterious effects on cardiac function. Reduced exercise capacity is largely mediated through skeletal muscle dysfunction at baseline and sympathetic over-activation may be important in pathogenesis.
心肌肥厚重构和收缩功能障碍是线粒体疾病患者的常见表现，且是发病率和早期死亡率的独立预测因素。耐力运动训练可改善症状和骨骼肌功能，但心脏适应性改变尚不清楚。
在 10 例 m.3243A>G 相关线粒体疾病的成年患者中，在训练前和训练 16 周后评估了运动能力、心脏磁共振成像和磷-31 谱、疾病负担、疲劳、生活质量、心率变异性（HRV）和血压变异性（BPV），并与年龄和性别匹配的久坐对照组进行了比较。基线时，患者的左心室质量指数（LVMI，p<0.05）和 LV 质量与舒张末期容积比增加，纵向缩短和心肌磷酸肌酸/三磷酸腺苷比值降低（均 p<0.01）。患者的峰值动静脉氧差（p<0.05）、摄氧量（VO2）和功率降低（两者均 p<0.01），但心输出量无显著差异。所有患者均保持稳定并完成了≥80%的训练课程。随着训练，患者和对照组的峰值 VO2、无氧阈和工作能力均有相似的比例增加。LVMI 在两组中均增加（p<0.01），但对心肌功能或生物能量学无显著影响。与对照组相比，患者在训练前后的 HRV 和 BPV 显示低频增加，高频减少（均 p<0.05）。
线粒体疾病患者和对照组在运动训练中均获得了相似的比例获益，无疾病进展或对心脏功能产生有害影响的证据。运动能力的降低主要是由于基线时骨骼肌功能障碍，而交感神经过度激活可能在发病机制中起重要作用。
