| Title: |
Oral digoxin effects on exercise performance, K+ regulation and skeletal muscle Na+, K+-ATPase in healthy humans |
| Authors: |
Sostaric, Simon; Petersen, Aaron; Goodman, Craig; Gong, Xiaofei; Aw, Tai-Juan; Brown, Malcolm J; Garnham, Andrew; Steward, Collene; Murphy, Kate T; Carey, Kate A; Leppik, James; Fraser, Steve F; Cameron-Smith, David; Krum, Henry; Snow, Rodney J; McKenna, Michael |
| Publisher Information: |
Wiley |
| Publication Year: |
2022 |
| Collection: |
Victoria University Melbourne: VU Eprint Repository |
| Subject Terms: |
4207 Sports science and exercise; Institute for Health and Sport; exercise science; exercise performance; skeletal muscle; digoxin; muscle performance |
| Description: |
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% (Formula presented.) and 67% (Formula presented.), 90% (Formula presented.) 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% (Formula presented.), 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% (Formula presented.) (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. (Figure presented.). Key points: The Na+,K+-ATPase (NKA) is vital in regulating skeletal muscle extracellular potassium concentration ([K+]), excitability and plasma [K+] ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| ISSN: |
0022-3751 |
| Relation: |
https://vuir.vu.edu.au/46752/; https://doi.org/10.1113/JP283017; https://vuir.vu.edu.au/46752/1/Oral%20digoxin%20effects%20on%20exercise%20performance,%20Ksup%2Bsup%20regulation%20and%20skeletal%20muscle%20Nasup%2Bsup%20,Ksup%2Bsup%20-ATPase%20in%20healthy.pdf; Sostaric, Simon ORCID logoorcid:0000-0003-0701-0992 , Petersen, Aaron ORCID logoorcid:0000-0003-1508-748X , Goodman, Craig ORCID logoorcid:0000-0002-5874-7743 , Gong, Xiaofei, Aw, Tai-Juan ORCID logoorcid:0000-0001-8363-9499 , Brown, Malcolm J ORCID logoorcid:0000-0003-1667-7801 , Garnham, Andrew ORCID logoorcid:0000-0001-8068-9300 , Steward, Collene ORCID logoorcid:0000-0002-7903-0346 , Murphy, Kate T ORCID logoorcid:0000-0003-1993-4367 , Carey, Kate A ORCID logoorcid:0000-0002-5748-0768 , Leppik, James ORCID logoorcid:0000-0002-3040-081X , Fraser, Steve F ORCID logoorcid:0000-0003-0202-9619 , Cameron-Smith, David ORCID logoorcid:0000-0002-0144-5816 , Krum, Henry ORCID logoorcid:0000-0002-0655-3015 , Snow, Rodney J ORCID logoorcid:0000-0002-4796-6916 and McKenna, Michael ORCID logoorcid:0000-0001-9998-0093 (2022) Oral digoxin effects on exercise performance, K+ regulation and skeletal muscle Na+, K+-ATPase in healthy humans. Journal of Physiology, 600 (16). pp. 3749-3774. ISSN 0022-3751 |
| DOI: |
10.1113/JP283017 |
| Availability: |
https://vuir.vu.edu.au/46752/; https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP283017; https://doi.org/10.1113/JP283017 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.11A16EFB |
| Database: |
BASE |