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Articles in PresS, published online ahead of print February 1, 2002
J Appl Physiol, 10.1152/jap.00686.2001
Submitted on July 5, 2001
Accepted on January 25, 2002
1 Departments of Anatomy & Physiology, Kansas State University, Manhattan, KS, USA
* To whom correspondence should be addressed. E-mail: musch{at}vet.ksu.edu.
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 concentrations of [3H]ouabain binding sites) in skeletal muscle is reduced and this reduction is correlated with peak oxygen uptake. The present investigation determined whether the concentrations of [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 weeks post-surgery in 23 myocardial infracted (MI) and 18 sham operated control (Sham) rats. 18 rats had moderate LV dysfunction (LVEDP<20 mmHg) and 5 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 a ~2 fold increase in both lung and RV weight. Run time to fatigue and maximal oxygen uptake (VO2max) were significantly reduced (decreased 39% and decreased 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 VO2max: r=0.93, n=13, P<0.01). In addition, run time to fatigue was significantly correlated with VO2max (r=0.87, n=15, P<0.01). The concentration of [3H]ouabain binding sites (Bmax,) was significantly reduced (21-28%) in the 3 muscles comprised primarily of oxidative fibers (soleus [S]: 259±14 vs. 18±17; plantaris [P]: 295±17 vs. 229±18; red portion of the gastrocnemius [RG]: 326±17 vs. 260±14 pmol/g wet tissue wt). In addition, Bmax was significantly correlated with VO2max (S: r=0.54, n=15, P<0.05; P: r=0.59, n=15, P<0.05; RG: r=0.65, n=15, P<0.01). These results suggest that down regulation 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.
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