Quantifying the relationship and contribution of mitochondrial respiration to systemic exercise limitation in heart failure.
Quantifying the relationship and contribution of mitochondrial respiration to systemic exercise limitation in heart failure.
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DOI：
10.1002/ehf2.13272
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发表时间：
2021-04
影响因子：
3.8
通讯作者：
Bowen TS
中科院分区：
文献类型：
--
作者：
Knuiman P;Straw S;Gierula J;Koshy A;Roberts LD;Witte KK;Ferguson C;Bowen TS
心力衰竭伴射血分数降低(HFrEF)可导致骨骼肌线粒体异常，从而导致运动受限；然而，特定的线粒体治疗靶点仍然缺乏。这项研究量化了HFrEF中不同的线粒体呼吸状态对预测运动限制的全身指标的关系和贡献。对22例男性高血压性肺功能衰竭患者进行坡道递增功率心肺运动试验，测定运动参数，包括最大肺摄氧量(V̇O2峰)、乳酸阈值(V̇O2LT)、二氧化碳通气当量(V̇E/V̇CO_2LT)、循环峰值功率(CircP峰)和峰值氧脉搏。取胸大肌活检，以评估线粒体的原位呼吸。包括复合体I、II和IV在内的所有线粒体状态和电子传递系统容量均与V̇O2峰值(r=0.40-0.64；P<0.05)、V̇O_2LT(r=0.52-0.72；P<0.05)和CircP峰(r=0.42-0.60；P<0.05)相关。多元回归分析显示，年龄、血红蛋白、左心室射血分数与Ets容量相结合可分别解释V̇O2峰变异性的5 2%和V̇O2LT变异性的80%，Ets容量(P=0.0 4)和复合体I(P=0.0 1)是模型中唯一显著的贡献者。HFrEF患者骨骼肌活检的线粒体呼吸状态与已建立的无创性周期功率心肺运动试验指标(包括V̇O2峰、V̇O2LT和CircP峰)独立相关。结合基线患者特征，V-̇-O2峰变异的50%以上可以用线粒体Ets容量来解释。这些数据提供了优化的线粒体靶点，可能会减轻HFrEF的运动限制。
Heart failure with reduced ejection fraction (HFrEF) induces skeletal muscle mitochondrial abnormalities that contribute to exercise limitation; however, specific mitochondrial therapeutic targets remain poorly established. This study quantified the relationship and contribution of distinct mitochondrial respiratory states to prognostic whole‐body measures of exercise limitation in HFrEF. Male patients with HFrEF (n = 22) were prospectively enrolled and underwent ramp‐incremental cycle ergometry cardiopulmonary exercise testing to determine exercise variables including peak pulmonary oxygen uptake (V̇O2peak), lactate threshold (V̇O2LT), the ventilatory equivalent for carbon dioxide (V̇E/V̇CO2LT), peak circulatory power (CircPpeak), and peak oxygen pulse. Pectoralis major was biopsied for assessment of in situ mitochondrial respiration. All mitochondrial states including complexes I, II, and IV and electron transport system (ETS) capacity correlated with V̇O2peak (r = 0.40–0.64; P < 0.05), V̇O2LT (r = 0.52–0.72; P < 0.05), and CircPpeak (r = 0.42–0.60; P < 0.05). Multiple regression analysis revealed that combining age, haemoglobin, and left ventricular ejection fraction with ETS capacity could explain 52% of the variability in V̇O2peak and 80% of the variability in V̇O2LT, respectively, with ETS capacity (P = 0.04) and complex I (P = 0.01) the only significant contributors in the model. Mitochondrial respiratory states from skeletal muscle biopsies of patients with HFrEF were independently correlated to established non‐invasive prognostic cycle ergometry cardiopulmonary exercise testing indices including V̇O2peak, V̇O2LT, and CircPpeak. When combined with baseline patient characteristics, over 50% of the variability in V̇O2peak could be explained by the mitochondrial ETS capacity. These data provide optimized mitochondrial targets that may attenuate exercise limitations in HFrEF.
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DOI：
10.1249/mss.0000000000002193
发表时间：
2020-04-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Karlsen, Trine;Videm, Vibeke;Prescott, Eva
通讯作者：
Prescott, Eva
影响因子：
39.3
作者：
Fuelster, Susann;Tacke, Matthias;von Haehling, Stephan
通讯作者：
von Haehling, Stephan
影响因子：
37.8
作者：
Guazzi, Marco;Arena, Ross;Lavie, Carl J.
通讯作者：
Lavie, Carl J.
影响因子：
3.8
作者：
Cattadori G;Segurini C;Picozzi A;Padeletti L;Anzà C
通讯作者：
Anzà C
影响因子：
3.8
作者：
Knuiman P;Straw S;Gierula J;Koshy A;Roberts LD;Witte KK;Ferguson C;Bowen TS
通讯作者：
Bowen TS