Oral digoxin effects on exercise performance, K+ regulation and skeletal muscle Na+,K+-ATPase in healthy humans
Journal article
Sostaric, Simon, Petersen, Aaron C., Goodman, Craig A., Gong, Xiaofei, Aw, Tai-Juan, Brown, Malcolm J., Garnham, Andrew, Steward, Collene H., Murphy, Kate T., Carey, Kate A., Leppik, James, Fraser, Steve F., Cameron-Smith, David, Krum, Henry, Snow, Rodney J. and McKenna, Michael J.. (2022). Oral digoxin effects on exercise performance, K+ regulation and skeletal muscle Na+,K+-ATPase in healthy humans. The Journal of Physiology. 600(16), pp. 3749-3774. https://doi.org/10.1113/JP283017
Authors | Sostaric, Simon, Petersen, Aaron C., Goodman, Craig A., Gong, Xiaofei, Aw, Tai-Juan, Brown, Malcolm J., Garnham, Andrew, Steward, Collene H., Murphy, Kate T., Carey, Kate A., Leppik, James, Fraser, Steve F., Cameron-Smith, David, Krum, Henry, Snow, Rodney J. and McKenna, Michael J. |
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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% VO2peak and 67% VO2peak, 90% VO2peak 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% , fatigue, 3 h after exercise). In DIG, in resting muscle, [3H]-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% VO2peak (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. |
Keywords | digoxin; exercise; muscle strength; ouabain; potassium; skeletal muscle fatigue; sodium-potassium pump |
Year | 2022 |
Journal | The Journal of Physiology |
Journal citation | 600 (16), pp. 3749-3774 |
Publisher | John Wiley & Sons Ltd |
ISSN | 0022-3751 |
Digital Object Identifier (DOI) | https://doi.org/10.1113/JP283017 |
PubMed ID | 35837833 |
Scopus EID | 2-s2.0-85135272914 |
PubMed Central ID | PMC9541254 |
Open access | Published as ‘gold’ (paid) open access |
Page range | 3749-3774 |
Funder | National Health and Medical Research Council (NHMRC) |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication dates | |
Online | 02 Aug 2022 |
Publication process dates | |
Accepted | 08 Jul 2022 |
Deposited | 06 Dec 2022 |
Supplemental file | License File Access Level Open |
Grant ID | 256603 |
https://acuresearchbank.acu.edu.au/item/8y88z/oral-digoxin-effects-on-exercise-performance-k-regulation-and-skeletal-muscle-na-k-atpase-in-healthy-humans
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License: CC BY 4.0 | |
File access level: Open |
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