我们调查了地高辛是否降低了肌肉Na+,K+-ATP酶(NKA),受损的肌肉表现和加剧的运动K+障碍。10名健康成年人摄入地高辛(0.25mg;DIG)或安慰剂(CON)14天,并进行股四头肌力量和疲劳性,手指屈曲(FF,105%峰值工作率,3×1分钟,第四回合疲劳)和腿部自行车(LC,在33%VO2峰值${\\rm{V}}_{{\\rm{O}}_{\\rm{2}}{\\rm{峰值}}}$和67%VO2峰值${\\rm{V}}_{\\rm{O}}_{\\rm{\rm}{\rm}2{\}峰值}90%VO2峰值${\\rm{V}}_{{{\\rm{O}}}_{\\rm{2}}{\\rm{峰值}}}$到疲劳)试验使用双盲,交叉,随机化,平衡设计。采集动脉(a)和肘前静脉(v)血液(FF,LC)和肌肉活检(LC,休息,67%VO2峰值${\\rm{V}}_{{\\rm{O}}}_{\\rm{2}}{\\rm{峰值}}}$,疲劳,运动后3小时)。在DIG中,在静息肌肉中,[3H]-哇巴因结合位点含量(OB-Fab)没有变化;然而,用Digibind去除结合的地高辛显示总的哇巴因结合(OBFab)增加(8.2%,P=0.047),表明NKA-地高辛占用率为7.6%。DIG股四头肌肌力下降(-4.3%,P=0.010),但疲劳性没有变化。在LC期间,在DIG(主要效应)中,疲劳时间和[K+]a不变,与CON相比,[K]v较低(P=0.042),[K]a-v较大(P=0.004);运动(主要影响),肌肉OB-Fab在67%VO2峰值时增加${\\rm{V}}_{{{\\rm{O}}}_{\\rm{2}}{\\rm{峰值}}$(每湿重,P=0.005;每个蛋白质P=0.001)和疲劳时(每个蛋白质,P=0.003),而[K+]a,[K+]v和[K+]a-v分别在疲劳时增加(P=0.001)。在FF期间,在DIG(主要效应)中,疲劳的时间,[K+]a,[K+]v和[K+]a-v不变;运动(主要效果),等离子体[K+]a,[K+]v,疲劳时,[K]a-v和肌肉K外排均增加(P=0.001)。因此,肌肉力量下降,但功能性肌肉NKA含量在DIG期间被保留,尽管血浆地高辛和肌肉NKA-地高辛占有率升高,K+干扰和疲劳性不变。关键点:Na+,K+-ATP酶(NKA)在调节骨骼肌细胞外钾浓度([K+])方面至关重要,兴奋性和血浆[K],从而也在强烈收缩期间调节疲劳。NKA被地高辛抑制,在心脏病患者中,这会降低肌肉功能性NKA含量([3H]-哇巴因结合)并加剧运动过程中的K干扰。在健康的成年人中,我们发现临床水平的地高辛令人惊讶地没有降低功能性肌肉NKA含量,而通过Digibind抗体去除地高辛显示肌肉总NKA含量增加~8%。因此,在剧烈运动期间,地高辛不会加剧动脉血浆[K+]紊乱或加重疲劳,虽然股四头肌肌力降低。因此,地高辛治疗健康参与者血清地高辛升高,但是肌肉功能性NKA含量被保留,而K+干扰和剧烈运动时的疲劳没有变化。对地高辛NKA抑制的这种弹性与NKA在保持K调节和肌肉功能中的重要性一致。
We investigated whether digoxin lowered muscle Na+ ,K+ -ATPase (NKA), impaired muscle performance and exacerbated exercise K+ disturbances. Ten healthy adults ingested digoxin (0.25 mg; DIG) or placebo (CON) for 14 days and performed quadriceps strength and fatiguability, finger flexion (FF, 105%peak-workrate , 3 × 1 min, fourth bout to fatigue) and leg cycling (LC, 10 min at 33% V O 2 peak ${\\rm{V}}_{{{\\rm{O}}}_{\\rm{2}}{\\rm{peak}}}$ and 67% V O 2 peak ${\\rm{V}}_{{{\\rm{O}}}_{\\rm{2}}{\\rm{peak}}}$ , 90% V O 2 peak ${\\rm{V}}_{{{\\rm{O}}}_{\\rm{2}}{\\rm{peak}}}$ to fatigue) trials using a double-blind, crossover, randomised, counter-balanced design. Arterial (a) and antecubital venous (v) blood was sampled (FF, LC) and muscle biopsied (LC, rest, 67% V O 2 peak ${\\rm{V}}_{{{\\rm{O}}}_{\\rm{2}}{\\rm{peak}}}$ , fatigue, 3 h after exercise). In DIG, in resting muscle, [3 H]-ouabain binding site content (OB-Fab ) was unchanged; however, bound-digoxin removal with Digibind revealed total ouabain binding (OB+Fab ) increased (8.2%, P = 0.047), indicating 7.6% NKA-digoxin occupancy. Quadriceps muscle strength declined in DIG (-4.3%, P = 0.010) but fatiguability was unchanged. During LC, in DIG (main effects), time to fatigue and [K+ ]a were unchanged, whilst [K+ ]v was lower (P = 0.042) and [K+ ]a-v greater (P = 0.004) than in CON; with exercise (main effects), muscle OB-Fab was increased at 67% V O 2 peak ${\\rm{V}}_{{{\\rm{O}}}_{\\rm{2}}{\\rm{peak}}}$ (per wet-weight, P = 0.005; per protein P = 0.001) and at fatigue (per protein, P = 0.003), whilst [K+ ]a , [K+ ]v and [K+ ]a-v were each increased at fatigue (P = 0.001). During FF, in DIG (main effects), time to fatigue, [K+ ]a , [K+ ]v and [K+ ]a-v were unchanged; with exercise (main effects), plasma [K+ ]a , [K+ ]v , [K+ ]a-v and muscle K+ efflux were all increased at fatigue (P = 0.001). Thus, muscle strength declined, but functional muscle NKA content was preserved during DIG, despite elevated plasma digoxin and muscle NKA-digoxin occupancy, with K+ disturbances and fatiguability unchanged. KEY POINTS: The Na+ ,K+ -ATPase (NKA) is vital in regulating skeletal muscle extracellular potassium concentration ([K+ ]), excitability and plasma [K+ ] and thereby also in modulating fatigue during intense contractions. NKA is inhibited by digoxin, which in cardiac patients lowers muscle functional NKA content ([3 H]-ouabain binding) and exacerbates K+ disturbances during exercise. In healthy adults, we found that digoxin at clinical levels surprisingly did not reduce functional muscle NKA content, whilst digoxin removal by Digibind antibody revealed an ∼8% increased muscle total NKA content. Accordingly, digoxin did not exacerbate arterial plasma [K+ ] disturbances or worsen fatigue during intense exercise, although quadriceps muscle strength was reduced. Thus, digoxin treatment in healthy participants elevated serum digoxin, but muscle functional NKA content was preserved, whilst K+ disturbances and fatigue with intense exercise were unchanged. This resilience to digoxin NKA inhibition is consistent with the importance of NKA in preserving K+ regulation and muscle function.