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J Appl Physiol 92: 2326-2334, 2002. First published February 1, 2002; doi:10.1152/japplphysiol.00686.2001
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Vol. 92, Issue 6, 2326-2334, June 2002

Skeletal muscle ouabain binding sites are reduced in rats with chronic heart failure

Timothy I. Musch, Swen Wolfram, K. Sue Hageman, and Joel G. Pickar

Departments of Anatomy, Physiology, and Kinesiology, Kansas State University, Manhattan, Kansas 66506-5802

Intrinsic skeletal muscle abnormalities decrease muscular endurance in chronic heart failure (CHF). In CHF patients, the number of skeletal muscle Na+-K+ pumps that have a high affinity for ouabain (i.e., the concentration of [3H]ouabain binding sites) is reduced, and this reduction is correlated with peak oxygen uptake. The present investigation determined whether the concentration of skeletal muscle [3H]ouabain binding sites found during CHF is related to 1) severity of the disease state, 2) muscle fiber type composition, and/or 3) endurance capacity. Four muscles were chosen that represented slow-twitch oxidative (SO), fast-twitch oxidative glycolytic (FOG), fast-twitch glycolytic (FG), and mixed fiber types. Measurements were obtained 8-10 wk postsurgery in 23 myocardial infarcted (MI) and 18 sham-operated control (sham) rats. Eighteen rats had moderate left ventricular (LV) dysfunction [LV end-diastolic pressure (LVEDP) < 20 mmHg], and five had severe LV dysfunction (LVEDP > 20 mmHg). Rats with severe LV dysfunction had significant pulmonary congestion and were likely in a chronic state of compensated congestive failure as indicated by an approximately twofold increase in both lung and right ventricle weight. Run time to fatigue and maximal oxygen uptake (VO2 max) were significantly reduced (down-arrow 39 and down-arrow 28%, respectively) in the rats with severe LV dysfunction and correlated with the magnitude of LV dysfunction as indicated by LVEDP (run time: r = 0.60, n = 21, P < 0.01 and VO2 max: r = 0.93, n = 13, P < 0.01). In addition, run time to fatigue was significantly correlated with VO2 max (r = 0.87, n = 15, P < 0.01). The concentration of [3H]ouabain binding sites (Bmax) was significantly reduced (21-28%) in the three muscles comprised primarily of oxidative fibers [soleus: 259 ± 14 vs. 188 ± 17; plantaris: 295 ± 17 vs. 229 ± 18; red portion of gastrocnemius: 326 ± 17 vs. 260 ± 14 pmol/g wet tissue wt]. In addition, Bmax was significantly correlated with VO2 max (soleus: r = 0.54, n = 15, P < 0.05; plantaris: r = 0.59, n = 15, P < 0.05; red portion of gastrocnemius: r = 0.65, n = 15, P < 0.01). These results suggest that downregulation of Na+-K+ pumps that possess a high affinity for ouabain in oxidative skeletal muscle may play an important role in the exercise intolerance that attends severe LV dysfunction in CHF.

Na+-K+ pump; exercise; performance; oxygen uptake; congestive failure


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