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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 (
O2 max) were
significantly reduced (
39 and
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
O2 max: r = 0.93, n = 13, P < 0.01). In addition,
run time to fatigue was significantly correlated with
O2 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
O2 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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