Publication
Oral digoxin effects on exercise performance, K
Publisher:
Wiley
Date:
08-2022
DOI:
10.1113/JP283017
Abstract: 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% and 67% , 90% to fatigue) trials using a double‐blind, crossover, randomised, counter‐balanced design. Arterial (a) and antecubital venous (v) blood was s led (FF, LC) and muscle biopsied (LC, rest, 67% , fatigue, 3 h after exercise). In DIG, in resting muscle, [ 3 H]‐ouabain binding site content (OB‐F ab ) was unchanged however, bound‐digoxin removal with Digibind revealed total ouabain binding (OB+F ab ) 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‐F ab was increased at 67% (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. image 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.